KR20230052771A - Biomarker for Pseudoexfoliation glaucoma - Google Patents

Abstract

The present invention provides a composition for diagnosing pseudoexfoliation glaucoma, a diagnostic kit, a method for providing information for diagnosis, a screening method for therapeutic agents, and a composition for prevention or treatment. It is expected that the present invention will be able to diagnose or predict the onset of the pseudoexfoliation glaucoma, and it is expected that the present can be usefully used in the development of a treatment agent for the pseudoexfoliation glaucoma by controlling the expression and activity of markers of the present invention, IL-8, MIP-1a, fractalkine and/or Flt3 ligand.

Description

Pseudoexfoliation glaucoma biomarker {Biomarker for Pseudoexfoliation glaucoma}

The present invention relates to the use of IL-8, MIP-1a, fractalkine and/or Flt3 ligand for predicting, diagnosing, and treating pseudoscale glaucoma.

Pseudoexfoliation syndrome is a disease in which extracellular matrix is abnormally produced and accumulated in the anterior segment structures of the eye, including the lens and iris, and connective tissue of the skin and organs, and is an aging-related disease frequently found in the elderly.

In pseudoscale syndrome, 'exfoliation material' caused by the production of abnormal extracellular matrix is characteristically found at the pupillary interface and anterior lens capsule. These 'exfoliating substances' can increase intraocular pressure (intraocular pressure) by various mechanisms and cause pseudoexfoliation glaucoma. In addition, it can affect the increase in intraocular pressure by physically closing the trabecular meshwork through which aqueous humor escapes, by degrading the function of cells constituting the trabecular meshwork and Schlemm's canal, or by changing the expression of aqueous humor proteins. .

The aqueous humor contains electrolytes, organic salts, growth factors, cytokines, etc., and plays a role in maintaining the metabolic balance of the anterior segment. In various ophthalmic diseases, this aqueous humor homeostasis can be disrupted, and growth factors and cytokines in the aqueous humor can be increased.

These growth factors and cytokines can change the cells constituting the intraocular structure related to the drainage of the aqueous humor, thereby increasing the resistance of the aqueous outflow path. It may promote production, and a vicious circle may be formed with each other.

Therefore, it is necessary to find a specific molecular or protein marker in the aqueous humor of pseudoscale glaucoma, and to research and develop a single or combined therapeutic agent targeting it.

KR 10-2020-0116145 A

The present inventors have tried to find pseudoscale glaucoma specific molecular or protein markers. The present inventors focused on the fact that the expression levels of various growth factors and cytokines (IL-8, MIP-1a, fractalkine and Flt3 ligand) were high in the aqueous humor (AH) of patients with pseudoscale glaucoma, and thus IL-8, MIP-1a, The present invention was completed by confirming the correlation between fractalkine and Flt3 ligand.

Accordingly, an object of the present invention is to treat Flt3 ligand, interleukin 8 (IL-8), macrophage inflammatory protein 1a (MIP-1a) and fractalkine from the group consisting of It is to provide a marker composition for predicting the onset of pseudoexfoliation glaucoma comprising a selected gene or a protein encoded by the gene.

Another object of the present invention is for diagnosing or predicting the onset of pseudoscale glaucoma, including an agent for measuring the level of mRNA of a gene selected from the group consisting of Flt3 ligand, IL-8, MIP-1a, and fractalkine, or a protein encoded by the gene. to provide a composition.

Another object of the present invention is to provide an information providing method for diagnosing or predicting the onset of pseudoscale glaucoma.

Another object of the present invention is to provide a screening method for a therapeutic agent for pseudoscale glaucoma.

Another object of the present invention is to provide a composition for preventing or treating pseudoscale glaucoma.

In the present invention, IL-8, MIP-1a, fractalkine, and Flt3 ligand, which were specifically overexpressed compared to normal subjects, were identified in biological samples (aqueous) obtained from patients with pseudoscale glaucoma, and these were obtained as diagnostic markers for pseudoscale glaucoma.

More specifically, the present invention analyzed the association between various growth factors and cytokines of pseudo scale glaucoma (XFG) patients and normal controls, primary open angle glaucoma (POAG), and pseudo scale syndrome (XFS) patients, and as a result, the other 3 It was confirmed that IL-8, MIP-1a, fractalkine, and Flt3 ligand values were significantly higher in the pseudoscale glaucoma patient group than in the group. In particular, Flt3 ligand had a positive correlation with IL-8, MIP-1a, and fractalkine. confirmed that there is

Accordingly, the present invention provides IL-8, MIP-1a, fractalkine, and Flt3 ligand as biomarkers for pseudoscale glaucoma.

The gene symbol of the biomarker Flt3 ligand of the present invention is "FLT3LG (fms related receptor tyrosine kinase 3 ligand)", the gene symbol of IL-8 (interleukin-8) is "CXCL8 (C-X-C motif chemokine ligand 8)", MIP- The gene symbol for 1a (Macrophage inflammatory protein 1a) is "CCL3 (C-C motif chemokine ligand 3)" and the gene symbol for fractalkine is "CX3CL1 (C-X3-C motif chemokine ligand 1)".

In the present invention, "biomarker of pseudoscale glaucoma" or "marker of pseudoscale glaucoma" means an organic biomarker that can diagnose pseudoscale glaucoma by showing an increase or decrease in cells, tissues, etc. with pseudoscale glaucoma compared to normal cells. Means a molecular substance, organic such as polypeptides or nucleic acids (eg, mRNA, etc.), lipids, glycolipids, glycoproteins, sugars (monosaccharides, disaccharides, oligosaccharides, etc.) that are increased or decreased in pseudoscale glaucoma patients compared to normal subjects biomolecules, etc. In the present invention, by checking the expression of IL-8, MIP-1a, fractalkine and/or Flt3 ligand at the mRNA level or protein level, pseudoscale glaucoma can be diagnosed or the possibility of pseudoscale glaucoma can be inferred.

In the present invention, "diagnosis" means to confirm a pathological state, and for the purpose of the present invention, the diagnosis is to determine whether a pseudoscale glaucoma diagnostic marker is expressed or not to progress from normal or pseudoscale glaucoma to pseudoscale glaucoma. In addition, the diagnosis in the present invention includes determining whether the onset, development, and reduction of pseudoscale glaucoma is confirmed by checking the expression and expression level of the pseudoscale glaucoma diagnostic marker.

According to one aspect of the present invention, the present invention provides Flt3 ligand, interleukin 8 (IL-8), macrophage inflammatory protein 1a (MIP-1a) and fractalkine It provides a composition for predicting the onset of pseudoexfoliation glaucoma comprising a gene selected from the group consisting of or a protein encoded by the gene.

The nucleotide sequence of the Flt3 ligand gene (Gene ID: 2323) is shown in SEQ ID NO: 1.

The nucleotide sequence of the IL-8 gene (Gene ID: 3576) is shown in SEQ ID NO: 2.

The nucleotide sequence of the MIP-1a gene (Gene ID: 6348) is shown in SEQ ID NO: 3.

The nucleotide sequence of the fractalkine gene (Gene ID: 6376) is shown in SEQ ID NO: 4.

According to another aspect of the present invention, the present invention is a false scale comprising an agent for measuring the level of mRNA of a gene selected from the group consisting of Flt3 ligand, IL-8, MIP-1a and fractalkine or a protein encoded by the gene A composition for diagnosing or predicting the onset of glaucoma is provided.

The agent for measuring the mRNA level of the gene is preferably a primer pair or a probe.

Specifically, a primer is a nucleic acid sequence having a short free 3' hydroxyl group that can form a base pair with a complementary template and serves as a starting point for template strand copying. means sequence.

If necessary, the primers of the present invention may include a label detectable directly or indirectly by spectroscopic, photochemical, biochemical, immunochemical, or chemical means. Examples of the label include enzymes such as horseradish peroxidase and alkaline phosphatase, radioactive isotopes such as 33P, chemical groups such as biotin, and fluorescent molecules.

A probe refers to a nucleic acid fragment such as RNA or DNA capable of specific binding to mRNA and being labeled so that the presence or absence of a specific mRNA can be confirmed. The probe may be manufactured in the form of an oligonucleotide probe, a single stranded DNA probe, a double stranded DNA probe, an RNA probe, or the like.

A person skilled in the art can use a primer pair that specifically amplifies a specific region of a gene or a probe that specifically recognizes a specific region of a gene in consideration of variables such as the degree of hybridization between sequences in a target gene from a nucleic acid sequence of a known gene. can design

The agent for measuring the level of the protein encoded by the gene is preferably an antibody, polyclonal antibody, monoclonal antibody and recombinant antibody that specifically binds to the protein of IL-8, MIP-1a, fractalkine and/or Flt3 ligand. includes all In addition, the antibody of the present invention is a complete form having two full-length light chains and two full-length heavy chains and functional fragments of antibody molecules, such as Fab, F(ab'), F(ab') 2 and Fv.

Since the nucleotide sequences of the IL-8, MIP-1a, fractalkine and/or Flt3 ligand genes of the present invention are registered in the gene bank, those skilled in the art can use antisense oligonucleotides that specifically amplify specific regions of these genes based on the sequences. , primer pairs or probes can be designed.

Antisense oligonucleotides, primers or probes of the present invention can be chemically synthesized using the phosphor amidite solid support method, or other well-known methods. Such nucleic acid sequences can also be modified using a number of means known in the art. Non-limiting examples of such modifications include methylation, capping, substitution of one or more homologues of the native nucleotide, and modifications between nucleotides, such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoro amidates, carbamates, etc.) or to charged linkages (eg phosphorothioates, phosphorodithioates, etc.).

According to another aspect of the present invention, the composition for diagnosing pseudoscale glaucoma of the present invention can be applied and manufactured as a kit for diagnosing or predicting the onset of pseudoscale glaucoma.

The kit for diagnosing or predicting the onset of pseudoscale glaucoma of the present invention may further include other components or devices widely used in the art.

Specific examples include primer pairs specific for the gene and, additionally, a test tube or other suitable container, a reaction buffer, deoxynucleotides (dNTPs), enzymes such as Taq-polymerase and reverse transcriptase, DNAse inhibitors, RNAse inhibitors, It can be made into a kit for RT-PCR, including DEPC-water, sterile water, and the like. As another example, a kit for a DNA chip including essential elements required to perform the DNA chip may be manufactured.

As another example, an antibody specific for the protein of the gene and, additionally, a reagent capable of detecting the bound antibody, such as a labeled secondary antibody, chromophores, enzymes and substrates thereof. It can be made into a kit for ELISA. As another example, it may be manufactured as a kit for a protein chip including essential elements required to perform a protein chip.

In addition to the kits exemplified above, various types of diagnostic kits manufactured as rapid diagnostic kits capable of detecting the gene are included.

According to another aspect of the present invention, the present invention provides an information providing method for diagnosing or predicting the onset of pseudoscale glaucoma, comprising the following steps:

measuring the expression levels of mRNAs of IL-8, MIP-1a, fractalkine and/or Flt3 ligand genes present in the biological sample or proteins encoded by the genes; and comparing the measured expression level with that of a normal control group.

In the present invention, the expression level of IL-8, MIP-1a, fractalkine and/or Flt3 ligand gene mRNA or protein encoded by the gene in a biological sample is measured, and the measurement result is compared with the expression level of a normal control sample. Thus, when the amount of a gene or protein in the sample increases, or there is a change in the presence or absence of the gene or protein, it can be determined as pseudoscale glaucoma or predicted to develop pseudoscale glaucoma.

The methods of the present invention include mammals, particularly humans. At this time, the human subject includes a person suspected of having pseudoscale glaucoma, a pseudoscale syndrome patient, or an unsuspected person who needs to be diagnosed with pseudoscale glaucoma.

In the present invention, "biological sample" may consist of tissues, cells, blood, serum, plasma, saliva and urine, but is not limited thereto.

In the present invention, "measurement of gene expression level" is a process of confirming the presence of mRNA of the gene and the level of expression in Aqueous Humor (AH) in order to determine the progress of pseudoscale glaucoma. It is made by measuring the amount of mRNA . Assay methods for this include, for example, reverse transcription polymerase reaction (RT-PCR), competitive reverse transcription polymerase reaction (Competitive RT-PCR), real-time reverse transcription polymerase reaction (Realtime RT-PCR), RNase protection assay (RPA; RNase protection assay), Northern blotting, DNA chip, etc., but are not limited thereto.

The agent for measuring the level of a gene in the present invention is preferably an antisense oligonucleotide, a primer pair or a probe. In the present invention, "antisense" refers to a sequence of nucleotide bases in which an antisense oligomer is hybridized with a target sequence in RNA by Watson-Crick base pairing, allowing the formation of typically mRNA and RNA:oligomeric heteroduplexes within the target sequence. and an oligomer having an inter-subunit backbone. Oligomers may have exact sequence complementarity or near complementarity to the target sequence. These antisense oligomers can block or inhibit translation of mRNA and alter the processing of mRNA to produce splice variants of mRNA.

In the present invention, "measurement of protein expression level" is a process of confirming the presence and expression level of the protein expressed from the gene of the present invention in Aqueous Humor (AH) in order to determine the progress of pseudoscale glaucoma. It is done by measuring quantity. Analysis methods for this include Western blot, ELISA (enzyme linked immunosorbent assay), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion method, rocket immunoelectrophoresis , tissue immunostaining, immunoprecipitation assay, complement fixation assay, flow cytometry (Fluorescence Activated Cell Sorter, FACS), protein chip, etc., but are not limited thereto. The agent for measuring the protein expression level in the present invention is preferably an antibody.

In the present invention, "detection" includes quantitative and / or qualitative analysis, and includes detection of presence, absence, and detection of expression level. Such methods are known in the art, and those skilled in the art are suitable for the practice of the present application. You will be able to choose your way.

According to another aspect of the present invention, the present invention is an IL-8, MIP-1a, fractalkine and / or Flt3 ligand gene mRNA or a substance that reduces the expression level of the protein encoded by the gene in the subject; It provides a screening method for a therapeutic agent for pseudoscale glaucoma comprising a.

In the present invention, the expression level of the IL-8, MIP-1a, fractalkine and/or Flt3 ligand gene mRNA or the protein encoded by the gene is measured in the subject, and when a candidate substance for pseudoscale glaucoma treatment is administered, the gene or protein If the expression level is reduced compared to the existing one, the candidate substance can be used as a pseudoscale glaucoma treatment.

According to another aspect of the present invention, the present invention provides a composition for preventing or treating pseudoscale glaucoma comprising an inhibitor of the expression or activity of IL-8, MIP-1a, fractalkine and/or Flt3 ligand.

According to one embodiment of the present invention, the composition of the present invention may be a pharmaceutical composition.

In the present invention, "prevention" means any action to suppress or delay the onset of pseudoscale glaucoma by administration of the composition of the present invention.

In the present invention, "treatment" refers to all activities that improve or beneficially change symptoms caused by pseudoscale glaucoma by administration of the composition of the present invention.

The pharmaceutical composition according to the present invention may include a pharmaceutically acceptable carrier in addition to the active ingredient. Examples of pharmaceutically acceptable carriers included in the pharmaceutical composition according to the present invention include saline, buffered saline, water, glycerol, polyethylene glycol, vegetable oil, isopropyl myristate, and ethanol, but are not limited thereto.

When formulating the pharmaceutical composition according to the present invention, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, troches, etc., and these solid preparations contain at least one excipient, for example, starch, calcium carbonate, sucrose, etc., to the peptide according to the present invention. It is prepared by mixing sucrose, lactose, or gelatin. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid preparations for oral administration include suspensions, internal solutions, emulsions, or syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives are used. can be included Formulations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspension solutions, emulsions, freeze-dried formulations, suppositories, and the like.

Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerol, gelatin, and the like may be used.

The composition according to the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally, or topically applied) depending on the desired method, and the dosage may vary depending on the patient's condition, body weight, and disease. Depending on the degree, drug form, administration route and time, it can be appropriately selected by those skilled in the art.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type, severity, and activity of the drug of the patient's disease , sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field.

The composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the composition according to the present invention may vary depending on the patient's age, sex, and weight, and is generally 0.001 to 150 mg per 1 kg of body weight, preferably 0.01 to 100 mg per day or every other day or daily. It can be administered in 1 to 3 divided doses. However, since it may increase or decrease depending on the route of administration, severity of obesity, gender, weight, age, etc., the dosage is not limited to the scope of the present invention in any way.

The features and advantages of the present invention are summarized as follows:

(a) The present invention provides a composition for diagnosis of pseudoexfoliation glaucoma, a diagnosis kit, a method for providing information for diagnosis, a method for screening a therapeutic agent, and a composition for prevention or treatment.

(b) It is expected that the present invention can diagnose pseudoscale glaucoma or predict the onset of pseudoscale glaucoma, and by regulating the expression and activity of IL-8, MIP-1a, fractalkine and/or Flt3 ligand, which are markers of the present invention, It is expected to be useful in the development of pseudoscale glaucoma treatment.

1 is a result of confirming the level of Flt3 ligand in aqueous humor measured using Magnetic Luminex Assay according to an embodiment of the present invention.
2 is a result of confirming the level of fractalkine in aqueous humor measured using Magnetic Luminex Assay according to an embodiment of the present invention.
3 is a result of confirming the level of IL-8 in aqueous humor measured using Magnetic Luminex Assay according to an embodiment of the present invention.
4 is a result of confirming the level of MIP-1a in aqueous humor measured using Magnetic Luminex Assay according to an embodiment of the present invention.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for explaining the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

Preparation Example 1. Aqueous Humor (AH) Sample Preparation

Aqueous (AH) samples of 50-100 μL were taken before cataract surgery from the eyes of 21 patients with pseudoscale syndrome, 28 patients with pseudoscale glaucoma, 14 patients with primary open-angle glaucoma, and 17 normal controls. did Waterproof samples were stored in a -80 °C freezer until analysis.

On the other hand, pseudoscale glaucoma was defined as when the following criteria were satisfied:

1) untreated intraocular pressure >21 mmHg;

2) Open angle findings on anterior chamber angular examination,

3) Glaucomatous optic nerve changes and corresponding visual field defect findings,

4) Identification of 'exfoliated material' present in the anterior capsule or pupil

For reference, pseudoscale syndrome was defined as a case where 'exfoliation material' was observed in the anterior capsule, but the intraocular pressure was normal and there was no glaucomatous optic nerve change. It was defined as the case where 'substance' was not observed.

In addition, patients with diabetic retinopathy, uncontrolled intraocular pressure (>21 mmHg), trabeculectomy or Ahmed tube insertion within 6 months, and patients who had used anti-inflammatory eye drops within 6 months were not included.

This experiment was approved by the Yeungnam University Hospital Clinical Trial Ethics Committee (IRB No. 2020-04-124), and consent was obtained from all patients.

Preparation Example 2. Statistical Analysis

Statistical analysis was performed using the R statistics package version 3.5.3. All values are expressed as mean ± SD or number (%).

In order to compare the concentrations of cytokines and growth factors, post hoc tests were performed using Kruskal-Wallis test and Dunn's test. A P value of less than 0.05 was considered statistically significant.

Example. Analysis of growth factors and cytokines in aqueous humor

First, the clinical characteristics (gender, age, intraocular pressure, and number of intraocular pressure lowering drugs) of patients with pseudoscale syndrome, patients with pseudoscale glaucoma, patients with primary open-angle glaucoma, and normal control eyes are shown in Table 1 below.

Variables Normal POAG XFS XFG P value Eyes(n) 17 14 21 28 - Sex (male/female) 8/9 7/7 8/13 16/12 0.63 Age (years) 70.1±9.7 71.0±6.6 72.3±7.6 74.3±8.7 0.31 IOP (mmHg) 13.8±3.2 13.9±1.8 15.0±3.1 13.3±2.7 0.25 Number of eye drops 0 1.8±0.5 0 1.5±1.2 0.27

IOP: intraocular pressure

POAG: Primary Open Angle Glaucoma

XFS: False Scale Syndrome

XFG: pseudoscale glaucoma

Next, a kit (Magnetic Luminex Performance Assay Base kit) was purchased from the manufacturer (R&D systems, Minneapolis, MN, USA) to analyze growth factors and cytokines contained in aqueous humor, and was used according to the manufacturer's instructions.

Analysis included the following growth factors and cytokines: MIP-1a, Fractalkine, Flt3 ligand, and IL-8.

Specifically, the aqueous sample is placed in a mixture of fluorescent magnetic beads coupled to an antibody specific to the target analyte, and a biotinylated detection antibody to the target analyte and phycoerythrin-binding streptavidin (phycoerythrin) conjugated streptavidin) was added and fluorescence was quantified using the Bio-Plex 200 system.

The concentrations of growth factors and cytokines were output as mass/volume (pg/mL). If the concentration was lower than the minimum limit of detection and was not detected, a value of 1/2 of the minimum limit of detection was applied for analysis.

Growth factor and cytokine detection rate (%) in aqueous humor according to Magnetic Luminex Assay Normal
(n=17) POAG
(n=14) XFS
(n=21) XFG
(n=28) Flt3 Ligand 58.8
(10/17) 57.1
(8/14) 71.4
(15/21) 85.7
(24/28) Fractalkine 100
(17/17) 100
(14/14) 100
(21/21) 100
(28/28) IL-8 100
(17/17) 100
(14/14) 100
(21/21) 100
(28/28) MIP-1a 82.4 (14/17) 78.6
(11/14) 100
(21/21) 92.9
(26/28)

Data are presented as percentage (%) and frequency (number/total number).

Growth factor and cytokine concentrations in aqueous humor Normal
(n=17) POAG
(n=14) XFS
(n=21) XFG
(n=28) IL-8 6.44±3.82 9.27±7.67 6.14±3.29 21.75±20.68 MIP-1a 10.66±5.35 9.82±6.29 16.34±5.48 21.88±10.28 Fractalkine 81.09±16.01 80.05±21.97 112.10±38.04 170.45±71.50 Flt3 Ligand 2.52±3.76 4.38±5.16 4.65±3.70 12.14±11.67

Data are presented as mean (pg/ml) ± standard deviation (SD).

Comparison of growth factor and cytokine concentrations in aqueous humor (P value) Normal
vs POAG Normal
vs XFS POAG
vs XFS Normal
vs XFG POAG
vs XFG XFS
vs XFG IL-8 0.446 0.917 0.454 0.000744 0.0279 0.000349 MIP-1a 0.995 0.0360 0.388 0.0000290 0.0000511 0.0408 Fractalkine 0.982 0.0370 0.0427 0.00000231 0.00000628 0.00825 Flt3 Ligand 0.517 0.219 0.582 0.000781 0.0191 0.0298

P values were calculated using the Kruskal-Wallis test followed by Dunn's multiple comparison test.

Correlation between growth factor and cytokine concentrations in aqueous humor, age of participants, and intraocular pressure IL-8 MIP-1a Fractalkine Flt3 Ligand age IOP IL-8 0 1.66E-05 1.35E-04 1.92E-07 0.227 0.0982 MIP-1a 0 1.94E-11 4.81E-02 0.476 0.204 Fractalkine - - 0 6.13E-02 0.0284 0.241 Flt3 Ligand - - - 0 0.488 0.241 age - - - - 0 0.203 IOP - - - - - 0

Data are presented as P values calculated using Spearman's correlation analysis.

As can be seen in Figures 1 to 5 and Tables 2 to 5, the expression of IL-8, MIP-1a, fractalkine, and Flt3 ligand was found in the remaining three (normal control group, pseudoscale syndrome, primary open angle) in the pseudoscale glaucoma patient group. glaucoma) was higher than that of the group. In addition, the concentrations of IL-8, MIP-1a, and fractalkine showed positive correlations with each other, and Flt3 ligand in particular showed positive correlations with other factors.

<110> Industry Academic Cooperation Foundation of Yeungnam University <120> Biomarker for Pseudoexfoliation glaucoma <130> PN210389 <160> 4 <170> KoPatentIn 3.0 <210> 1 <211> 12004 <212> DNA <213> fms related receptor tyrosine kinase 3 ligand <400> 1 gtctctggct gtcacccggc ttggcccctt ccacacccaa ctggggcaag cctggtgcgt 60 gaggagactt ggactctagg tccccaaggg gcggagccag ggtccccact cctggggcag 120 ggggagcaga gggtgggggg ctgggttccc gggtccctaa cctggggagg gttctgggga 180 ccagacgtcg aggttcttag aagtggagat gaagagtttt caccgtaact ggggcagacg 240 caggaagcct gggggaggaa ggggcggaaa ctcagccaca tcaatgggac gcgggagggg 300 cggggaggca aaggggcggg cagggcaggg gctggggcat gagggtccga gacttgttct 360 tctgtccctt ccaagacccg gcgacaggag gcatgagggg cccccggccg aaatgacagt 420 gctggcgcca gcctggagcc caacagtgcg taaaccccag ggacaagatc aggggagagg 480 ggaggcacaa tgtcaggatg gggcagagat gaggggagat ggacgggaga acagatggac 540 agatgacgag gaaataggag gggagatgga cagatgtgag gggagatgga taggagagga 600 gacggacaga ggagggggag atggacagag gatggggaga tggacagagg agggggagat 660 agaggagagg gagatagaga ggagtgggag atggacagga gcggggagat ggacagagga 720 gggggagatg gacagaggag agggcagatg aacagaggag agggagataa agaggaggga 780 ggtggacagg aggagggaga tggacagaga agggggagat ggacagaggt gggggagatg 840 gacaggaggg aagatggaga ggagggggta tggacagagg agaggggaga tggacaggag 900 ggggagatgg acagaggaga gggagatgaa gaggaggggg aggtggacag gaggagggag 960 acggacagag gagaggaaga gagacagagg aggggggaga tggacagagg agggggagat 1020 ggacagaaaa ggggggagat ggacagagga gagggaaggt ggacagagcc aagaacaaat 1080 gaagaggacg tggaccaaga tcaagagaga agcaggcaac agtggtgtag aaggcagagg 1140 gagggacaga gctggaggaa cccgggcgag gaaaccagac gtgaagatga ggtggttgga 1200 gagagaccag cagagtgggg gagatgggga gagagagggg tggggcagag ggggatgcaa 1260 actggacagc attggaccag aggcagagag aaaccgggaa agacaggcag agatggggcc 1320 atgtctccag aaagtgtgga agaggcagaa ggacacccag ggaaggagga gcggggaaga 1380 cagaacagta caggtgggaa gcccggagga gggggctgtg tgtggaacag cagagggctc 1440 ccccagcacc cgctcccctg cagacctatc tcctcctgct gctgctgctg agctcgggac 1500 tcagtgggac ccaggactgc tccttccaac acagccccat ctcctccgac ttcgctgtca 1560 aaatccgtga gctggtgagc ggcgctgccc cggaccccct catgtgatcc cccttccccc 1620 cacttttttt tttaagtaga gatggggtct ctctccctgt gtttcccagg gtggtcttga 1680 actcctgggc tcaagcgatc ctcccacctt ggcctcccaa agtgctggaa ttacaggcgt 1740 gagccactgt gcttaggggt gtcatccctt tttaagggca aggttctgtg gcttcttctg 1800 ggctccccct ctcttggtct tgtccctctc tctctggatc tctgctgcca cctctgggtc 1860 cccacagttc tgtttctcgc tgttttcagc caggcctgat cctgttttct cccgcagtct 1920 gactacctgc ttcaagatta cccagtcacc gtggcctcca acctgcagga cgtaagtcat 1980 gttgggaggg acctgggatg gaggtgggga ccacagactc aagatgctcc accgaggcga 2040 gtggataacc aggccctccc ctccccaaac ccaggaatca gagtcctcag cccctcctcc 2100 ctcagaccca ggagccccgg cccagcccct cctccctcag acccagcagc cccgtgccca 2160 gctcctccct cagacccgtg ggttctcccc tctaggagga gctctgcggg ggcctctggc 2220 ggctggtcct ggcacagcgc tggatggagc ggctcaagac tgtcgctggg tccaagatgc 2280 aaggcttgct ggagcgcgtg aacacggaga tacactttgt caccaaatgt gcctttcagg 2340 tcagccctca acttagggga caagtgaggg gagggagatg ccttcctacg aattagaagt 2400 aaagctccac taggccttat tggcgatttg gaccatagcc acccaacgaa ggtagagcga 2460 gaagcgccac cctgcagagc cctgttccta cagaacaaca cgtccccagg caccggtgat 2520 ggggagcagt ctggtcccat tctggggccc cggtttccta ggccatgatg aagggtgcca 2580 ctgaggggtt cttcccccaa aaaaaaacag ggagagaagg ggtctctaaa ctgaggaggc 2640 cgggcgtggt ggctcactcc tgtaatccta gcactttggg aggctgaggt gggcggatca 2700 cttgaggtca ggagtttgag accagcctgg ccaacatgat gaaatcccgg ctgtactaaa 2760 aatacaaaaa ttagccgggc atggtggctc aggaggctga ggcacaggaa tcgcttgaac 2820 ccgggagcca gaggctgcag tgagccgaga tcatgccact gcactccagc ctgggagaca 2880 gagtgaaact gtctcaaaaa caaaacaaac aaacaaaaac ctctctctga gggctgggtg 2940 cagtggctca cacctgtaat cccagcactt tcggaggcca aggtgggagg attatttgag 3000 cccaggagtt caagaccagc ccgggtaaca cagtgaaacc tcatctctgc acaaaaataa 3060 aaataaatta gccaggcatg gtggtgccca cctgtggtcc cagctactca gaaggctgag 3120 gtgggaggat cacttgagcc ctggaggtcg aggctgcgat gagctatgat tgggccactg 3180 cactccagct tgagcgacag agcaagaccc tgtctcaaaa catagaatag gccgtgtatg 3240 gtggctcacg actgtaatcc cagcactttg ggaggctgag gcgggtggat tgcctgagct 3300 caggagttcg agaccagcct cggcaacgtg atgaaaacca tctctactaa aatacaaaaa 3360 caaaattagc caggcatggt ggtgggcacc tgtagtccca gctacttggg agactgaggc 3420 aggagaattg cttgaaccca ggaggcagag gttgcagtga gccgagatca caccactgcc 3480 ctccagcctg ggcgacagag caagactcca tctccaaaaa aataaaaata aaataaaagc 3540 ctgggtacag tggctcacgc ctgtaatccc agcactttgg gagcccgagg cgggcagatc 3600 acgaggtcag gagtttgaga ccaccctggc caatgtggtg aaaccccgtc tctactaaaa 3660 atacaaaaat tagctgggca tggtggcgcg cgcctgtagt cccagctact caggaggctg 3720 aggcagaatt ccttgaaccc gggaggtaga agttgcagta agccgagatc gtgccactgt 3780 actccagcca gggtgacaga gcaagactct gtccccaaaa aataaataaa taataaagta 3840 actttgggag gccgaggcgg gcgagtcacc tgaggtcagg agttcgagac cagcctggcc 3900 aacatagaga aaccccgttt ctactaaaaa atataaataa ataaataaat aaataaatag 3960 gctgggcacg gtggctcacg cctgtaatcc cacactttgg gaggccgagg cgggcggatc 4020 acaaggtcag gagatcaaga ccatcctggc taacacaatg aaaccccatc tctactaaaa 4080 atacaaacaa ttagccgggc gtggtggcag gcgcctgtag tcccaactac ctgggaggct 4140 gaggcaggtg aatggcgtga aaccaggagg cggagcttgc agtgagccga gattgcgcca 4200 ctgtactcca gcctgggcaa cagagcgaga ctctgtctta aaaataaata aataaataaa 4260 tatggccaag cacggtggct catgcctaca atcccagcac tttgggaggc caaggtgggc 4320 agatcacctg aggtcaggag ttcgagacca gcctggccaa catggagaaa ccccgtctct 4380 actacaaata caaaaaatag ctgggcatgg tggtgggcac ctatagtccc aaccactgag 4440 gaggctgagg caggagaatc acttgaacct gggaggcaga ggttgcattt caccactcca 4500 gcctgggcaa cagagtgaga ctctatctca aaaaaaaatt aattaattaa ataaataaac 4560 tctgagagcc agagctcact gggccctgtt gctgggcatc gccagcaggg aagggccttt 4620 ggcctgcgga ggggcggtgg ggggatgacg tggtggtgac gtctccctcc cctgctccca 4680 gccccccccc agctgtcttc gcttcgtcca gaccaacatc tcccgcctcc tgcaggagac 4740 ctccgagcag ctggtggcgc tgaagccctg gatcactcgc cagaacttct cccggtgcct 4800 ggagctgcag tgtcagcccg gtaaaggctt ccaggcaccc ccactccttc ccctcctgtc 4860 ctcacggccg ctcctcctct ctgcacagtg catcccagac cccatctttc tcatattggt 4920 tgtgacaagg gcaagcttat tcctctttct ggagctcagt ttaccaattt tttttttttt 4980 tttttgagac ggagtctcgc actgtcgccc aggctggagt gcagtggcgt gatcttggct 5040 cactgcaagc tccgcctctc gggttcatgc cattctcctg cctcagcctc ccaagtagct 5100 gggaccacag gcgcccgcca ccacacccgg ctaatttttt gtatttttag tagagacggg 5160 gttttaccga gttaaaccag gatggtctcg atctcctgac cttgtgatcc acctgccttg 5220 gcctcccaaa gtgctgggat tacaggcgtg agccacagtg cccagcctac cttttttttt 5280 tttttttttt ttgagatgga gtcttgctct gtcccccagg ctggagtgca ggggtgctat 5340 ctcggctcac tgcaagctct gcctcctggg ttcacgccat tctcttgcct cagcctcccc 5400 agcagctggg actacaggcg cctgccacct cacgcggcta attttttttt ttgtattttt 5460 agtagagacg gtgtttcacc gtgtcagcca ggatggtctc gatctcctga cctcgtgatc 5520 tgcccgcctc ggcctcccaa agtgctagga ttacagatgt gagccaccgc gcccagccta 5580 ttgttttttt tttctaagtc ggagtcttgc tctgtcgccc aggctggagt gcagtggcgc 5640 aatcttggct cactgcaacc tccatctcca gggttcaagc gaatcttctg cctcagcctt 5700 ccgagtacct gggattacag atgcgcatac catgcctggc tagtttttgt gtttttagta 5760 gagatgggtt ttcaccatgt tggccaggct ggtcttgaac tcctgacctc aagtgatcca 5820 cccaccttgg cctcccaaag tgctgggatt ataggcgtga gccaccgcgc tcagcctatt 5880 cactcattta atttgtgaca gtctgatgag gtaggtacaa tgattatcct agttttacag 5940 atgagcaaac tgaggcacag agaggccaag cagcccatcc aaggtcacac agccagtggc 6000 agccaggcct ctctttcctt ccttacccca gcccttctcc ttggtcaccc agcctcctct 6060 ttctccccag actcctcaac cctgccaccc ccatggagtc cccggcccct ggaggccaca 6120 gccccgacag ccccgcagcc ccctctgctc ctcctactgc tgctgcccgt gggcctcctg 6180 ctgctggccg ctgcctggtg cctgcactgg cagaggacgc ggcggaggac accccgccct 6240 ggggagcagg tgagcaggct gggaagaggg ggtgaggggg ccgagagggt ggcccacttg 6300 tggctgacac tttggggccc acaggtgccc cccgtcccca gtccccagga cctgctgctt 6360 gtggagcact gacctggcca aggcctcatc ctggtgagtc cttcctgggc tatggggcct 6420 ggactttgtg tctgcaggtt gggagggtca ctaggaggcc atggaagggt ggtgagcagt 6480 ggaggggcag gggcagctct aggtgcagaa agacccctct ggggccaggc gcggtggctc 6540 acgcctgtaa tcccagcact ttgggaggcc gaggcgggtg gatcacttga ggtcaggagt 6600 tcaagaccag cctggccaac atggcaaacc ccagtctcta ctaaaaatac aaaaattaac 6660 tgggcatagt ggtgtgtgcc tgtaatccca gctactcagg aggctgagga aggagaattg 6720 cttgaaccca ggaggcggag gttgcagtga gccgagattg cgccactgga ctccagcctg 6780 agtgacagag ctagactccg tctcaaaaaa aaaaaaaaaa aagaaaagga aagacccctc 6840 tggggccacg gagacagact ggagaccaag ccggaggctg tgggaaggcc cagggtgagg 6900 accatgactg agccagggct gggaccatgg gatggagtgg agtggatggg cagagagtca 6960 ggggtcagag atcaggaggg accggcctgg ggcctgacag gcttgagttg gcacagatag 7020 ccctggtcca gtgatggggt ggacaggggg gaacctgggg gaggagtcag attagggaaa 7080 gacatggagc tcactgggga cctgaaggag caaggggccc tggggagatc tgtggatgtg 7140 ggagtttgca agcctcctgg gacaggaagg aaatggcatt ccagaaagag ggaactgcct 7200 ttggaagccc tttggtatga gaaagctcag ggtgttccag taacttgggc cagcgtgggg 7260 cagcaaggag ccatgggagg tgtgagaggg aggaaaggag ctgggaacag gtgtggaggg 7320 tgcaggcagg taggcaggtg ggccaggagg gaagaaggag gggaggcccc agcgggtccc 7380 ctaacatttc aaatctaaca ttttgtagta attgctcgca catatagtgc cttggtaatg 7440 caggcctcat gtggggctgg cttgcttgct ttattttttt ttgagatgga ctctcactct 7500 gtcacccagg ctggagtgca gtggcgggat cttggctcac tgcaacctcc acctcccagg 7560 ttcaagcaat tctcctgcct cagcctccca agtagctggg attacaggcg cccgccacca 7620 tgcctggcta attttttgta tttttagtag agatggggtt tcgccatgtt ggccaggctg 7680 gtctcaaact cctgatctca gctgatccgc ccgcctcagc ctcccaaagt gctgggatga 7740 caggtgtgag ccactgttcc tggcccatgc tgggctttcc acaaatgaac tcacttcctt 7800 gagaagttcg tgccattatg atcccaaggc atagagaggt aaataatttg ccaaaagtca 7860 cacagctcaa gggtgacaac caagatttga cttcaggttg tctttttttt ttttttgaga 7920 tggagtcttg ctctgtcgcc caggctgtag tgcagtggca tgatctcggc tcactgcagc 7980 ccccgcctcc caggttcaag tgattctcct gcctcagcct ctggagtagc tgggattaca 8040 ggtacccacc accacactcg gctaattttt gtatttgtag tagagacggg gtttcaccat 8100 gttggccagg ctggtctcga actcctgacc ttagctgatc cgcccgcctc agcctcccaa 8160 agtgctggga ttacaggcat gagccaccac gcccggcctc gagtttgtct tgatccagca 8220 tctgtgccct tcactctgct gcctcagttt cctgatctgt acaaaaggct ctaataatag 8280 tccttccacc atagggttgt tatggggtga agtgaagtga cacaggcaag gctcttagag 8340 caacgcagtg gaaacggcat gtgagccacc tgtgcgattt tcactttcct ggtagccaca 8400 tttttttttt ttttttcctg agatggagtc tcactctgtc gccaggttga agtgcagtgg 8460 tgtgatctca gctcactgca acctccacct cccgggttca agcgattctc ctgcttcagt 8520 ctaccgagta gctgggatta caggcacgcg ccatcacgcc cggctaattt tttgtgtttt 8580 tagtagagac aaggtttcac catgttggtc aggctggtct cgaactcctg acctcatgat 8640 ccacccgcct cagcctccca aagtgctggg attacaggcg tgagccaccg cgcccggggt 8700 cacagttttt aaaaaaggaa aaagaagcag gtaactttat tttatgcagt atatccaaaa 8760 tgttgttatt tcaacatgta atcagtattt ctcaatgatt aatgagacat taatcagttg 8820 gaatcattca tcattttggg atattttaca ttcttttgtc atactaagcc ttcagcatcc 8880 aacgtatagt ttatttattt atttattttt ccttttgaga tggattctcg ctctgtcacc 8940 caggctggag tgcagtggcg cgatctcagc tcactgcaac ctcggactcc ctggttcagg 9000 cgattctcct gcctcagcct cccgagtacc tgggattacg ccaccacacc cagctaattt 9060 ttgtactttt agtagagacc gggtttcacc atgttggcca ggatgatctc catcccctga 9120 cctcgtgatc cgcccgcctc agcctcccaa agtgctggat tacaagtgta agccaccgcg 9180 cccagcccag acaataaatt tttatcagaa atgcttcatc tatatttaaa tttcatgaaa 9240 tttacagttg ccaaaagtag actcacatag tcaagttgtt caaaacatac attaaaccag 9300 cctgggccac atggtgaaac cccatctcta caaaaaattt taaaaagtag ctgggtgtgg 9360 tggcacatgc ctgcagtccc agctacttag gaggcaaagt aggaggattg cttgagccca 9420 ggaggtcgag gctgcagtga gccctgattg tgccactgca ctccagcctg ggtgagagag 9480 caagaccctg tctcaaaaac aaaaaaacca cacagaagag tttagaatcc cagttgctat 9540 ctctgggaat catcatgatt gctaagaccg gtatctatcc aacaacaaca aaaataatta 9600 gtgcactcca gcctgggcaa tagagggaga ctctgtctca aaaaaaaaaa aaaaaaaaaa 9660 aaaaagatca aagaccagta tctaaattgc tctgtcgccc agggtggagt gcagtggcac 9720 gatctcggct cactgcaacc tccgcctccc gggttcaagt gattctcctg cctcagcctc 9780 cccagtagct tggactacag gcgcgtgcca ccacacccag ctaatttttg tatttttagt 9840 agaggtaggg tttcactatg tttgccagga ttgtctcgat ctcttgacct cgtgatctgc 9900 ccgcctcagc ctcccaaagt gctgggatta taggcgtgag ccaccacgcc cagcctatct 9960 tttttttttt ttttaagaaa aggtaataca ttgagcagtt ttcctcccaa cctagtccct 10020 gtccaatctg tttcctgtct taaatttatt ttttattata attttttttt tttttttttt 10080 ttgtgagaca gacttttgct cttgttagcc aggctggagt gcagtggtgc tatcttgact 10140 cacggcaacc tccacctccc aggttcaagc gattctcctg cctcagcctc tggagtagct 10200 tggattacaa gcgcctgcca ccacgcccaa ctaatttagt gtatttttag tagagacggg 10260 gtttcttttg ttgttgttgt tgtttttgag acggagtctc actctattgc ccaggctgga 10320 gtgcaacggc acgatctcgg ctcactgcaa catctgcctc ccgggttcaa gcgattctac 10380 tgcctcagcc tcctgagtag ctgggattac aggcacacac caccacacct ggctaatttt 10440 tgtattttta gtagagatgg ggtttcacca tattggccag gctgatctcg aactcctgac 10500 ctcgtgatct gcccgccttg acctcccaaa gtgataggat tacagccatg agccgccctg 10560 cccaactaat acctgatatt aattttattg tatctcaccc agcatggtgg ctcacacctg 10620 taactccttg gcagatcgct tgagcctaag agttcaagac cagcttgggc aacatggtga 10680 aaccccgtct ctactaaaaa tataaaaatg agctgggcat ggtggcgtgc acccgtaatc 10740 ccagctaact caggaggctg aggcaggaag aatggcttga acccgggagg cagaggctgc 10800 agtgagctga gatcatgcca ctgcattcca gcctgaaaca gagcaagact gtctcaaaag 10860 aagtttaagt ccagcctcaa actcctggac tcaagtgatc ctcctgcctc agcctcctga 10920 gtagtgcacc ggccccatct caagtgttca gtattcacat gtggcttgtt actcccgtat 10980 taaagagcaa aaatagagaa cgtttctttt tctttttttt cttttttttt ttttttttga 11040 gatgggagtt tcgctcttgt cgcccaggct ggagtgcaat ggcacgatct tggctcaccg 11100 caacctctgc ctcccaggtt caagcgattc tcctgcctca gcctcccaag tagctgggat 11160 tacagacatg caccaccatg cctagcaaat tttgtttttg tttttgtttt tttcttttga 11220 gacagacttt tgcttttatt gccaaggctg gagtgcaatg gtgcaatctc gactcactgc 11280 aacctccgcc tcccgggttc aagcaattct cctgcctcag ctaattttgt agttttagta 11340 gaaacggttt ctccatgtta gctaggctgg tctcaaactc ccaacctcag gtgatccgcc 11400 cgcctcgacc tcctaaagtg ctggaattac aggcgtgagc cactgtgcct ggccctaatt 11460 ttgtattttt agtagagatg gggtttctcc ctgttggtca ggctggtctc aaactcccaa 11520 cctaaggtga tccaccagcc tcagcctccc aaactgctgg gattataggc atgagccacc 11580 gcgcccgggg aaatataggg aacatttcta tcatggccac gttctcttgg acagcaatgc 11640 cctagcacat agtaagcgct tgctgggaat ggagttgttt tgggcataaa tctgtggccc 11700 gccccaagct aagctacttt ccctctcctc tctcagcgga gccttaaaca acgcagtgag 11760 acagacatct atcatcccat tttacagggg aggatactga ggcacacaga ggggagtcac 11820 cagccagagg atgcatagcc tggacacaga ggaagttggc tagaggccgg tcccttcctt 11880 gggcccctct cattccctcc ccagaatgga ggcaacgcca gaatccagca ccggccccat 11940 ttacccaact ctgtacaaag cccttgtccc catgaaattg tatataaatc atccttttct 12000 acca 12004 <210> 2 <211> 3148 <212> DNA <213> interleukin 8 <400> 2 acaaactttc agagacagca gagcacacaa gcttctagga caagagccag gaagaaacca 60 ccggaaggaa ccatctcact gtgtgtaaac atgacttcca agctggccgt ggctctcttg 120 gcagccttcc tgatttctgc agctctgtgt gaaggtaagc acatctttct gacctacagc 180 gttttcctat gtctaaatgt gatccttaga tagcaaagct attcttgatg ctttggtaac 240 aaacatcctt tttattcaga aacagaatat aatcttagca gtcaattaat gttaaattga 300 agatttagaa aaaactatat ataacactta ggaaagtata aagtttgatc aatatagata 360 ttctgctttt ataatttata ccatgtagca tgcatatatt taacgtaaat aagtaattta 420 tagtatgtcc tattgagaac cacggttacc tatattatgt attaatattg agttgagcaa 480 ggtaactcag acaattccac tccttgtagt atttcattga caagcctcag atttgtcatt 540 aattcctgtc tggtttaaag ataccctgat tatagaccag gcatgtataa cttatttata 600 tatttctgtt aattctttct gaaggcaatt tctatgctgg agagtcttag cttgcctact 660 ataaataaca ctgtggtatc acagaggatt atgcaatatt gaccagataa aaataccatg 720 aagatgttga tattgtacaa aaagaactct aactctttat ataggaagtc gttcaatgtt 780 gtcagttatg actgtttttt aaaacaaaga actaactgag gtcaagggct aggagaatat 840 tcaggaatga gttcactaga aacatgatgc cttccatagt ctccaaataa tcatattgga 900 attagaaagg aagtagctgg cagagctgtg cctgttgata aaatcaatcc ttaatcactt 960 tttcccccaa caggtgcagt tttgccaagg agtgctaaag aacttagatg tcagtgcata 1020 aagacatact ccaaaccttt ccaccccaaa tttatcaaag aactgagagt gattgagagt 1080 ggaccacact gcgccaacac agaaattatg taagtacttt aaaaaagatt agatattttg 1140 ttttagcaaa cttaaaatta aggaaggtgg aaatatttag gaaagttcca ggtgttagga 1200 ttacagtagt aaatgaaaca aaacaaaata aaaatatttg tctacatgac atttaaatat 1260 ggtagcttcc acaactacta taaatgttat tttggactta gactttatgc ctgacttaag 1320 gaatcatgat ttgaatgcaa aaactaaata ttaatctgaa ccatttcttt cttatttcag 1380 tgtaaagctt tctgatggaa gagagctctg tctggacccc aaggaaaact gggtgcagag 1440 ggttgtggag aagtttttga agaggtaagt tatatatttt ttaatttaaa tttttcattt 1500 atcctgagac atataatcca aagtcagcct ataaatttct ttctgttgct aaaaatcgtc 1560 attaggtatc tgcctttttg gttaaaaaaa aaaggaatag catcaatagt gagtttgttg 1620 tactcatgac cagaaagacc atacatagtt tgcccaggaa attctgggtt taagcttgtg 1680 tcctatactc ttagtaaagt tctttgtcac tcccagtagt gtcctatttt agatgataat 1740 ttctttgatc tccctattta tagttgagaa tatagagcat ttctaacaca tgaatgtcaa 1800 agactatatt gacttttcaa gaaccctact ttccttctta ttaaacatag ctcatcttta 1860 tatttttaat tttattttag ggctgagaat tcataaaaaa attcattctc tgtggtatcc 1920 aagaatcagt gaagatgcca gtgaaacttc aagcaaatct acttcaacac ttcatgtatt 1980 gtgtgggtct gttgtagggt tgccagatgc aatacaagat tcctggttaa atttgaattt 2040 cagtaaacaa tgaatagttt ttcattgtac catgaaatat ccagaacata cttatatgta 2100 aagtattatt tatttgaatc tacaaaaaac aacaaataat ttttaaatat aaggattttc 2160 ctagatattg cacgggagaa tatacaaata gcaaaattga ggccaagggc caagagaata 2220 tccgaacttt aatttcagga attgaatggg tttgctagaa tgtgatattt gaagcatcac 2280 ataaaaatga tgggacaata aattttgcca taaagtcaaa tttagctgga aatcctggat 2340 ttttttctgt taaatctggc aaccctagtc tgctagccag gatccacaag tccttgttcc 2400 actgtgcctt ggtttctcct ttatttctaa gtggaaaaag tattagccac catcttacct 2460 cacagtgatg ttgtgaggac atgtggaagc actttaagtt ttttcatcat aacataaatt 2520 attttcaagt gtaacttatt aacctattta ttatttatgt atttatttaa gcatcaaata 2580 tttgtgcaag aatttggaaa aatagaagat gaatcattga ttgaatagtt ataaagatgt 2640 tatagtaaat ttattttatt ttagatatta aatgatgttt tattagataa atttcaatca 2700 gggtttttag attaaacaaa caaacaattg ggtacccagt taaattttca tttcagataa 2760 acaacaaata attttttagt ataagtacat tattgtttat ctgaaatttt aattgaacta 2820 acaatcctag tttgatactc ccagtcttgt cattgccagc tgtgttggta gtgctgtgtt 2880 gaattacgga ataatgagtt agaactatta aaacagccaa aactccacag tcaatattag 2940 taatttcttg ctggttgaaa cttgtttatt atgtacaaat agattcttat aatattattt 3000 aaatgactgc atttttaaat acaaggcttt atatttttaa ctttaagatg tttttatgtg 3060 ctctccaaat tttttttact gtttctgatt gtatggaaat ataaaagtaa atatgaaaca 3120 tttaaaatat aatttgttgt caaagtaa 3148 <210> 3 <211> 1888 <212> DNA <213> Macrophage inflammatory protein 1a <400> 3 agaaggacac gggcagcaga cagtggtcag tcctttcttg gctctgctga cactcgagcc 60 cacattccgt cacctgctca gaatcatgca ggtctccact gctgcccttg ctgtcctcct 120 ctgcaccatg gctctctgca accagttctc tgcatcacgt gagtctgagt ttcgttgtgg 180 gtatcaccac tctctggcca tggttagacc acatcaatct tttcttgtgg cctaaaagcc 240 cccaagagaa aagagaactt cttaaagggc tgccaaacat cttggtcttt ctctttaaga 300 cttttatttt tatctctaga aggggtctta gccccctagt ctccaggtat gagaatctag 360 gcaggggcag gggagttaca gtccctttta cagatagaaa aacagggttc gaaacgaatc 420 agttagcaag aggcagaatc cagggctgct tacttcccag tggggtatgt tgttcactct 480 ccagctcact ctaggtctcc caggagctct gtcccttgga tgtcttatga gagatgtcca 540 aggcttctct tgggttgggg tatgacttct tgaaccagac aaaattccct gaagagaact 600 gagataagag aacagtccgt tcaggtatct ggatcacaca gagaaacaga gaacccacta 660 tgaagagtca aggagaaaga aggatacaga cagaaacaaa gagacatttc tcagcaaaaa 720 tgcccaaatg ccttccagtc acttggtctg agcaagcctg ccttcctcaa ctgctcgggg 780 atcagaagct gcctggcctt ttcttctgag ctgtgactcg ggcttattct cttcctttct 840 ccacagttgc tgctgacacg ccgaccgcct gctgcttcag ctacacctcc cggcagattc 900 cacagaattt catagctgac tactttgaga cgagcagcca gtgctccaag cccggtgtca 960 tgtaagtgcc agtcttcctg ctcacctcta tggaggtagg gagggtcagg gttggggcag 1020 agacaggcca gaaggccatc ctggaaaggc ccagccttca ggagcctatc ggggatacag 1080 gacgcagggc tccgaggtgt gacctgactt ggagctggag tgaggcatgt gttacagagt 1140 caggaagggc tgccccagcc cagaggaaag ggacaggaag aaggaggcag cgggacactc 1200 tgagggccac ccctactgag tcactgagag aagctctcta gacagagata ggcagggggc 1260 ccctgaaaga ggagcaagcc ctgagctgcc caggacagag agcagaatgg tggggccatg 1320 gtgggcccag gattcccctg ctggattccc cagtgcttaa ctcttcctcc cttctccaca 1380 gcttcctaac caagcgaagc cggcaggtct gtgctgaccc cagtgaggag tgggtccaga 1440 aatatgtcag cgacctggag ctgagtgcct gaggggtcca gaagcttcga ggcccagcga 1500 cctcggtggg cccagtgggg aggagcagga gcctgagcct tgggaacatg cgtgtgacct 1560 ccacagctac ctcttctatg gactggttgt tgccaaacag ccacactgtg ggactcttct 1620 taacttaaat tttaatttat ttatactatt tagtttttgt aatttatttt cgatttcaca 1680 gtgtgtttgt gattgtttgc tctgagagtt cccctgtccc ctcccccttc cctcacaccg 1740 cgtctggtga caaccgagtg gctgtcatca gcctgtgtag gcagtcatgg caccaaagcc 1800 accagactga caaatgtgta tcggatgctt ttgttcaggg ctgtgatcgg cctggggaaa 1860 taataaagat gctcttttaa aaggtaaa 1888 <210> 4 <211> 12555 <212> DNA < 213> Fractalkine <400> 4 aaggggacag cactgagctc tgccgcctgg ctctagccgc ctgcctggcc cccgccggga 60 ctcttgccca ccctcagcca tggctccgat atctctgtcg tggctgctcc gcttggccac 120 cttctgccat ctgactgtcc tgctggctgg taagtggggc ttgacttggg cacaaacagg 180 gtagggagcc cccagcccct tgtctatccc tcaagcctga catcaggggc cccagaccct 240 gcctgggtaa agctcaaggc cggtggcagc cgcttcccca gggatgtgcg agagggggct 300 gggcacctcg cttcccccag atgcagcgct ggacagattt ccagttgcca gcgaccgccc 360 tgcctggccc agcgagcaaa gtggctgtgc ctggaagcac agagaggtgg tgtgggtggc 420 ataagggagc caggtgtggg tgtgccagga gggcgggggt ggagagagcc tgcagaagct 480 cctgctgggc actggggtgg gaggccctgg ctgacagtgg ctggctcttt ccatcaagcg 540 ttaatgtgta acccgcagcc ctggccctgg gccaggccac agttgggact ttctcctgtc 600 ctgttttcaa agcccccagg attagggggc ccaggaccag tgaaggtcaa ggtcactgca 660 gctcatggtt ggggcttgcc actgctgtgc tagtctatag ccccagttgc tctgcctgtg 720 tctacccgtc atgctgtctt cctcctccaa gcacagtgta gaaaatgctt ttgcctctag 780 tcacttgctt actgaagccc aggacctggt aggggtacat aattaaccat cctacctgat 840 atggataaga tggaggccca gagaggttta gaaactggcc tgacaatgca cagccagcaa 900 gtagggcagg agaaggtaag acacatggga ctgaatgcag gagagagcac agatgcacac 960 tcaccacctc tgtgggccac atcacctcca tgaaccgcta gccagccccc tcctcaggga 1020 gtgcccccac catctggcag ggtgaccttc agagaaggtg ggcacacagc aagtctggga 1080 gaatgagaag tagtccccac tgtccagata tttccatgga gcaaactcac cctggggcag 1140 ggagcaggtg tgtgggtggg tgggcacgtg agagtggtgg aggcaaattc ctgctggctt 1200 cctgctgtct gggctggggc cctgaagcct gaggtgtctg cggacagtga gatctggaaa 1260 gcagggagtc agatggcggc tgctttgcca cagtcctgtt atgtgaccgt gagcagggtc 1320 ttgcctcctc tggtcccagt tgctgcatct ttaaatatag ctattacctc tccggtggat 1380 tgggggaggg tgacgaggtt ccaatgccta tggaggtgtt ttgaagaggg cggaggagga 1440 ggattacttt tactaagctg agagagggaa gggtcctagg ctaggatgga aaggggacac 1500 tgggggaccc tgggtgctca gactagcagc ctgaggcttt agaaccaggc ttctgccctc 1560 atcttggtca ttggctttac tggaagatcc tgggcattat tggaaccttt ctcagcctca 1620 ctttctcctc ctgtaaaact aggcatttga ccaggctcac cttggaagtc ctctcccacg 1680 ctgacatgta tggctctgag aggccctcgg gagcccctgt aggacaaggg ggtggtttgg 1740 aagccagaga gaccccgaga ggaggctggg gggttcgtag ctgctgccct gactagtgtg 1800 gggcagctgc gtcagtcccc aaatgtgggt ttgtggggct gtgtcaggca ggaggcttct 1860 gtactttata taacaaacct gcagctacga gtcagtgcag agcattgccc ccccactcca 1920 agagctgacg cattcactcc cactcaagtc ctggcaagaa agagaaaaaa aaacgaatct 1980 gttttaagct cctatagcct acccgcctca ttagcagtgg gggtggatgg ggagggcatg 2040 ggaggataaa ttcaagagtg tcagatccag gcccctgtct aatttaaata aaaattcctc 2100 catttttctg ttggttaagg tattatgcca caaagcgctt ccttaggcat tttgtccatt 2160 cattcaacaa atagttattg gacacctact gtgtgacaaa cctggttcta ggtactgggg 2220 cggcatcaat aaataaaaca gccaaggacc tcagccctcg aggtgctgta attcaactgc 2280 agaggacaca taacacacaa agtaaatcag taaacaatgt ggtctgttgg aaggagaaaa 2340 ggcactgtga taaaaaaata gagaggggtg gctgggcgca ggggctcatg cctgtaatcc 2400 cagcacattg ggaggccaag gcgggcagat cacctgacgt caggagttca agaccagcct 2460 ggccaacatc atgaaaccct gtctctacta aaaatataaa attagctggg tgtggtggtg 2520 catgcctgta gtcccagcta cttgggaggc tgaggcaaga gaatcgcttg aacctgggag 2580 gcagaggttg gagtgagccg agatcgtgtc actgcactcc agcctgggtg acagagtgag 2640 agtccattta aaaaaaaaaa aaagaaagaa aagaaaagaa aaagaaaaat agagagggga 2700 gaagagaggt gttgacattt taaatagggg gttagggaag cccactgagt aggtggcttt 2760 gcacagtttg gagcggggtg agggcgggag ccatgtggat atctctagag caatggtcct 2820 cagtgagtaa ttttgctccc ctatgggcca tttggcaatt tctagagaaa ttttttactt 2880 gttacaaata tcccaatgtt tttggttcag ttgagctact cgcctctagt gtgtagaggc 2940 cagagatgct gccaaacctc ctatagtacc cgggacagcc cccaaaacaa agaattgtct 3000 ggtccaaaat gtcagtagtg tcactgttga gaaaccttgc cctaagggaa aaatgctcca 3060 gaagttaaaa aattcttatt ctcacaacca cactgtgaag caggtattgt cacatccatt 3120 ttacaagtaa ggaaactgag gctcagggag tccgagtgac ttgctcagga cacacagctg 3180 ggcaatggct caagccctcc ctttatcacc tcatccagca acccaggaca tttcctgagt 3240 ctccttctaa gaccctggaa gactcttaga agtccttgag gtccagccta aaggagaatt 3300 cctccaagaa gcctcccctg accatttgaa gttggaagtg gtctctccct catgtaaacc 3360 ccaatatgtt tgtggtatgt tctggaacac tgtgtttcta cctggcatct agggtagcct 3420 agaacagtgg ggtgtttagg ggctgagtag aaaactagct ctgccaccat gcagctgtgt 3480 ggcactgggc acatttagcc tctcttattt ccagcttctg catctgtaaa gttgggataa 3540 tactcccttt gcaggaatgt tgggaattaa agagagcaga tgtgtacatg ctggacacag 3600 ggtccaatac acagtaggtg ttcaattaaa aaaaataaat aaaacctctg atactttgtg 3660 tgcctaattt acctgtccat caggctggga gccttctgag gccagaggca ttccttgttc 3720 atctcactgt acctcacagc acccagcaca gggcctggca agaggaacca gcatttgttg 3780 gttgactgaa taaacagagt gatctgatgg catttattgg gatggaagca ctctcttcaa 3840 actcagcacc agtgcctatg ggagaaagag ctcaaggtta aggataagag ggcctgagat 3900 ttttgtatat actcaaaagt aattccagcc agtgttggct gaatcaggaa gtggatggat 3960 ggatggatgg atggatggat ggatggatgg atggatggat gggtggatag atggatgaat 4020 ggatggatgg atggatgggt ggatggatgg acagatggat ggatggaaga agggatgggg 4080 aggggatgat gagggatgga tgagtaggtg agataaaagg gggcggaaga ttgacaggtg 4140 gtaggtaggg gagagggagt gggtagatgg atgaatggag atgaataggg gttgggcagg 4200 aggtggcagg tgggcgagga atgggtagaa gattgataag agtgggtgga cgggtggatg 4260 gataggtaga tagatgcatt aaagagagat aagtaaactg agactaattt cattcaatga 4320 atattgattg agtatccacc ttgtgcttga tgctgggaaa ctatgatacc aagacagaca 4380 aggtccctgc cttcctgaca ctcctatgac agataatata tgactggctg gatgaggcat 4440 tgtctccatt tacagaaagg aaaatttcag ctctgagaag ggacaggctc cccaggtcag 4500 ttaaacaatc ttcctggcag aaccaagaac tgagccgggc caggaccatt cagggaccgt 4560 ggcagagggt ggggactttg gagacaggat gactctgtgg ctctttaaag ccctggaggt 4620 gggcaatggc ttttcccatc ttggatttgg ggagcacaga atggaccttc tttcctatcc 4680 attgggcagc ctcccttgcc tcctcctgtc tctggtcact caggggcacc gtattttctg 4740 gggcttccca aagaagacac ctgcaggcca ttttagggga ctgccacctg gctccactca 4800 atagggcctg gggaggctgc aggtgagtca gtctgaggtt ccattgcaga aggagggtgg 4860 ccagcccaca cagtgacttt tatatcctgg ttactcagag agaaaggaca gccctgtgac 4920 ctggggagcc cctcctgcac acagccccca accccctgaa gctactagtg cttctccttg 4980 atgactcaac ccagacctgc cggccctaaa ccaccttccc acaaagcagg gtgggccaaa 5040 gctaaggggg agcgatggag agaggaagca gcagactcta caaagtctct ctgtgtgtgc 5100 aagcgtgcat gtgcctgtat ttgggaaagt ggtgtatgtt tgcatggcca catatatgta 5160 aatatttatg catgagcagt tcgtgttctg gtggagccca gggatgccct gggggtttcc 5220 caggctctga agggctagat aagatcagct tgctctcttg actgccctgg tctccagatg 5280 tttgcaaaac cctctggggt cttgcttttg ctgcatataa ccttgactca gatctgaaac 5340 tcaagctctt ccttgttttt tatactcatc ctccttgagc tcaagctaag cagaagaaaa 5400 tttgctggag attatagagg aagagaaaag gtggaaattc aatgtaaaca acttcaaatg 5460 tttatatcaa atagttgggt ttatttgtcc tgtcccgggg tttctctctg gttccacgtg 5520 acactcagct actgcctgcc ccttccgccc cactctgccc ccaccttatt cataccgtcc 5580 atctccaacc ctcctcctta ctcttcttgc tccaggaatt tcaaatgcct cttccctcct 5640 aggcaggatg actcagtacc tttcagcaac tgctctcggg ctcattctgg ctctcagcag 5700 cagaacaaag gatcatctat tcagcagacc ccaccttcct tagaaagcag ttgtacttat 5760 atatttttta aaaagtttat tgctgggcat agtggcttac atctgtaatc ccagctattc 5820 cggaggttga agtgggagaa tcacttgcgg tcggggttca agaccagcct gggcaacata 5880 gcaagaccct gtctcttaaa aaaattagcc aggcatggta gcaggcacct gtagtcccag 5940 ctacttggga ggctgaggca agagatctct tttttttttt tctttttttt ttgagacgga 6000 gtcttgttct gtcacccagg ctttagtgca gtggtatgat ctcagctcac tgcaacctct 6060 gcctcccgga ttcaagcaat tctcctgtct cagcttcccg agtagctggg actaaaggtg 6120 cacaccatca tgccaggcta atttgtgtat ttgtagtaga gacaaggttt caccatattg 6180 atcaggctgg tctcaaactc ctgacctcag atgatctatc tgtctcggcc tcccaaagtg 6240 ctgggattac aggtgtgagc caccgcaccc ggccaggagg atttcttgag cccaggattt 6300 tgaggttgcc gtgagctagg attataccac tgcactccag cctgggcaac agaacaagac 6360 cctatctctt aaaaaaaaat ggcagcggga agaaataagg cagaggtgag gggataggca 6420 aggccacagg cccggtgggg actagagcag gagaacctgc tccatcactt gctggctgtg 6480 tgaccttagc aggtccctgt cactctcaga ttcatccccc ctgctgcaca atggaccact 6540 taattttaaa aattaactcg ggcatggtgg ctcacgcctg taatcccagc actttgggag 6600 gccaaggagg gcagatcacc tgaggtcggg agtctgagac cagcctgacc aacatggaga 6660 aaccccgtct ctactaaaaa tacaaaatta gccaggagtc gtggcacatg cctgtaatcc 6720 cagctattcg ggagtctgag gcaggagaat cgcttgaatc tgggaggccg aggttgcggt 6780 gagccgagat catgccattg cactccagcc tgggcaacaa gagcaagact ccaactcaaa 6840 aaaaaaaaaa ttaaactctt aatatgtgcc aggcaaaaag aactctataa ataagaattc 6900 acgtttctta ttcttacaac aagactatga ggtagatgct atttttgttc ctattttaca 6960 ggtggggaaa ctgaggcata gagaagtttg gcaggggagg gaggctgagt caaaggcctt 7020 gaaggccagg gtgtacaggg gatcagtttt ggcttgggtg gtgtggccgg gacaatctgg 7080 cacggggttg ggaagccaga tgcccacaga catccctgct gaccaggaac ctctttgaac 7140 tcaggacagc accacggtgt gacgaaatgc aacatcacgt gcagcaagat gacatcaaag 7200 atacctgtag ctttgctcat ccactatcaa cagaaccagg catcatgcgg caaacgcgca 7260 atcatgtagg tactgccctc gaggcctctg aaatcccctt tgggcccttg gaatattccc 7320 agacctctga gaatctacgt ccacacctcc gctcccagac ctgggctccc agccaaaggc 7380 ctcagcacac gcttctcttg cccctggcct gcaggccacc tcactgacct taatttctgt 7440 gccacatggc taaggtggag agtggcttcc tgaatggccc agtgtggctg ggtggcagcc 7500 accctggctt gtggcctgga gcagccatga agggtggtaa ttcctcctgg gctgaagcac 7560 atgttacccc acactcgaac ccactatatt tcatggggcg gtgtgggtag gtgtaaagca 7620 tgagggtctt acttaaaatg caggttccag actctaacag acctgatgca aatcctgcct 7680 tccctcttac tggctgggtg gccctgcttc cattgcttac tttttgcaac ttggtttcct 7740 tgtctgtaaa atgggtagct aggacaggat gtaactaaag tgcttggcaa gggcgcggtg 7800 gctaatgcct gtaataccag cacttttgaa ggccgaggtt ggtggatcac ttgaggccag 7860 gagttcaaga ccaggctggc caacacggtg aaaccccatc tctactaaaa atacaaaaac 7920 tagcctggca tggtggtggg cgcctgtaat cccagctact cgggaggttg aggcaggaga 7980 atcgcttgaa cccaggatgc ggaggttgca gtgagccaag atggcaccac tgcactctgg 8040 cctgggcaac attgtgagac tccatctcaa aaaaaagaaa aagacaaaga aaagtaaata 8100 aagtgcctgg cagggtgctg tcagtaggag ctgcagaaat cactatctcc attggacaga 8160 caggaaacga ccatttcgag actttgggga gggattgagc cattgtaacc ctggctgttg 8220 aagaccctgg caatcttggt cacttgctcc tcctgggggc tctcttgggt cctgtctaac 8280 cagccagccc tgaggccttt ccccaggact gacttttggg acctaaagca gcctcagcca 8340 gacctagagg ccgggcagca ggaaatggcc aatggccctt tgctttctag gcccagctaa 8400 aggaagtctg gcacttcctc tcctcaatta tgcagtttct aaggtgggca aggtactgag 8460 tgtgctcctg ccggacctct ttgctgatca gtcaaggctt acttctccaa gacaccccca 8520 agtatttttt gttttctaga tgaaggggaa gaaggaagtt ggggagggga tcactgtgcc 8580 cagggggcct gcagggtcat acttgcttcc tggacttctc tggtttcccg gcatcctgga 8640 gccagatgcc tttacttcac ctctctgagc cttggtttcc tcatctgtaa aatggggatg 8700 agcctggtag ccaccttgtg gaatggatgt aaggtttaga catgggcaaa atgccaagca 8760 caggccgtgg catggagcca gggcctctgt cagctctgag ctgtgggctt ggtggtgaac 8820 tagccacaca gggcttcaga ggaagttcaa gatttggagg gcgctcggga tcccagtgag 8880 gctgccacat atttggctct agccccttct gcccgtgaac acacatcagg aggggaggag 8940 aggggcccgg agcacagcct gtagctgtga aaccgaagga gaggagcaac aagactcaca 9000 aagtctcata aggcctgttc cagagtgagg aggccccata cagagctcac ctgaagtccc 9060 ccccagcaga agactcaaag cccagagccc cctgccttaa tggtaacaat attatcgaca 9120 ttgttattat tttcagctat tactgatcta ctctgagctg ggtgcttcac ataatttacc 9180 tttttttaca gtaacacaga agtagggtga tcaactcgtc cgtgtttgcc tggggacttc 9240 cccagtttta aaatggaaag tcccccatcc taagcacccc ctccatccca atttttctgg 9300 gatggctggt caccctacag atgggaggct ttcctatctc catttctagg gtgaggacct 9360 ggatgctcag gagagcgggt tgccccagct ggtcagttgc ctcacagacg ctaagtggga 9420 ggacagggtt tccagccggg tgtgttcacc tgcagagtat tggtgctgtg cccccacacc 9480 acgctggccc gggtttctgg tatctgggca taaccgaatc cctgtcttcc tcccttgtag 9540 cttggagacg agacagcaca ggctgttctg tgccgacccg aaggagcaat gggtcaagga 9600 cgcgatgcag catctggacc gccaggctgc tgccctaact cgaaatggcg gcaccttcga 9660 gaagcagatc ggcgaggtga agcccaggac cacccctgcc gccgggggaa tggacgagtc 9720 tgtggtcctg gagcccgaag ccacaggcga aagcagtagc ctggagccga ctccttcttc 9780 ccaggaagca cagagggccc tggggacctc cccagagctg ccgacgggcg tgactggttc 9840 ctcagggacc aggctccccc cgacgccaaa ggctcaggat ggagggcctg tgggcacgga 9900 gcttttccga gtgcctcccg tctccactgc cgccacgtgg cagagttctg ctccccacca 9960 acctgggccc agcctctggg ctgaggcaaa gacctctgag gccccgtcca cccaggaccc 10020 ctccacccag gcctccactg cgtcctcccc agccccagag gagaatgctc cgtctgaagg 10080 ccagcgtgtg tggggtcagg gacagagccc caggccagag aactctctgg agcgggagga 10140 gatgggtccc gtgccagcgc acacggatgc cttccaggac tgggggcctg gcagcatggc 10200 ccacgtctct gtggtccctg tctcctcaga agggaccccc agcagggagc cagtggcttc 10260 aggcagctgg acccctaagg ctgaggaacc catccatgcc accatggacc cccagaggct 10320 gggcgtcctt atcactcctg tccctgacgc ccaggctgcc acccggaggc aggcggtggg 10380 gctgctggcc ttccttggcc tcctcttctg cctgggggtg gccatgttca cctaccagag 10440 cctccagggc tgccctcgaa agatggcagg agagatggcg gagggccttc gctacatccc 10500 ccggagctgt ggtagtaatt catatgtcct ggtgcccgtg tgaactcctc tggcctgtgt 10560 ctagttgttt gattcagaca gctgcctggg atccctcatc ctcataccca cccccaccca 10620 agggcctggc ctgagctggg atgattggag gggggaggtg ggatcctcca ggtgcacaag 10680 ctccaagctc ccaggcattc cccaggaggc cagccttgac cattctccac ctgccaggga 10740 cagagggggt ggcctcccaa ctcaccccag ccccaaaact ctcctctgct gctggctggt 10800 tagaggttcc ctttgacgcc atcccagccc caatgaacaa ttatttatta aatgcccagc 10860 cccttctgac ccatgctgcc ctgtgagtac tacagtcctc ccatctcaca catgagcatc 10920 aggccaggcc ctctgcccac tccctgcaac ctgattgtgt ctcttggtcc tgctgcagtt 10980 gccagtcacc ccggccacct gcggtgctat ctcccccagc cccatcctct gtacagagcc 11040 cacgccccca ctggtgacat gtcttttctt gcatgaggct agtgtggtgt ttcctggcac 11100 tgcttccagt gaggctctgc ccttggttag gcattgtggg aaggggagat aagggtatct 11160 ggtgactttc ctctttggtc tacactgtgc tgagtctgaa ggctgggttc tgatcctagt 11220 tccaccatca agccaccaac atactcccat ctgtgaaagg aaagagggag gtaaggaata 11280 cctgtccccc tgacaacact cattgacctg aggcccttct ctccagcccc tggatgcagc 11340 ctcacagtcc ttaccagcag agcaccttag acagtccctg ccaatggact aacttgtctt 11400 tggaccctga ggcccagagg gcctgcaagg gagtgagttg atagcacaga ccctgccctg 11460 tgggccccca aatggaaatg ggcagagcag agaccatccc tgaaggcccc gcccaggctt 11520 agtcactgag acagcccggg ctctgcctcc catcacccgc taagagggag ggagggctcc 11580 agacacatgt ccaagaagcc caggaaaggc tccaggagca gccacattcc tgatgcttct 11640 tcagagactc ctgcaggcag ccaggccaca agacccttgt ggtcccaccc cacacacgcc 11700 agattctttc ctgaggctgg gctcccttcc cacctctctc actccttgaa aacactgttc 11760 tctgccctcc aagaccttct ccttcacctt tgtccccacc gcagacagga ccagggattt 11820 ccatgatgtt ttccatgagt cccctgtttg tttctgaaag ggacgctacc cgggaagggg 11880 gctgggacat gggaaagggg aagttgtagg cataaagtca ggggttccct tttttggctg 11940 ctgaaggctc gagcatgcct ggatggggct gcaccggctg gcctggcccc tcagggtccc 12000 tggtggcagc tcacctctcc cttggattgt ccccgaccct tgccgtctac ctgaggggcc 12060 tcttatgggc tgggttctac ccaggtgcta ggaacactcc ttcacagatg ggtgcttgga 12120 ggaaggaaac ccagctctgg tccatagaga gcaagacgct gtgctgccct gcccacctgg 12180 cctctgcact cccctgctgg gtgtggcgca gcatattcag gaagctcagg gcctggctca 12240 ggtggggtca ctctggcagc tcagagaggg tgggagtggg cccaatgcac tttgttctgg 12300 ctcttccagg ctgggagagc cttccagggg tgggacaccc tgtgatgggg ccctgcctcc 12360 tttgtgagga agccgctggg gccagttggt cccccttcca tggactttgt tagtttctcc 12420 aagcaggaca tggacaagga tgatctagga agactttgga aagagtagga agactttgga 12480 aagacttttc caaccctcat caccaacgtc tgtgccattt tgtattttac taataaaatt 12540taaaagtctt gtgaa 12555

Claims (13)

A gene selected from the group consisting of Flt3 ligand, interleukin 8 (IL-8), macrophage inflammatory protein 1a (MIP-1a), and fractalkine, or the gene A marker composition for predicting the onset of pseudoexfoliation glaucoma, comprising a protein that encodes. The marker composition according to claim 1, wherein the Flt3 ligand gene consists of the nucleotide sequence of SEQ ID NO: 1. The marker composition for predicting the onset of pseudoscale glaucoma according to claim 1, wherein the IL-8 gene consists of the nucleotide sequence of SEQ ID NO: 2. The marker composition according to claim 1, wherein the MIP-1a gene consists of the nucleotide sequence of SEQ ID NO: 3. The marker composition according to claim 1, wherein the fractalkine gene consists of the nucleotide sequence of SEQ ID NO: 4. A composition for diagnosing or predicting the onset of pseudoscale glaucoma comprising an agent for measuring the level of mRNA of a gene selected from the group consisting of Flt3 ligand, IL-8, MIP-1a and fractalkine or a protein encoded by the gene. The composition for diagnosing or predicting the onset of pseudoscale glaucoma according to claim 6, wherein the agent for measuring the mRNA level is a primer pair or probe specific for the gene. The composition for diagnosing or predicting the onset of pseudoscale glaucoma according to claim 6, wherein the agent for measuring the protein level is an antibody specific to the protein. A kit for diagnosing or predicting the onset of pseudoscale glaucoma, comprising the composition of any one of claims 6 to 8. A method of providing information for diagnosing or predicting the onset of pseudoscale glaucoma, which includes the following steps:
Measuring the expression level of mRNA of a gene selected from the group consisting of Flt3 ligand, IL-8, MIP-1a and fractalkine present in a biological sample or a protein encoded by the gene; and
Comparing the measured expression level with that of a normal control group. 11. The method of claim 10, wherein the biological sample is selected from the group consisting of tissue, cell, blood, serum, plasma, saliva and urine. Screening for a therapeutic agent for pseudoscale glaucoma comprising the step of selecting a substance that reduces the expression level of the mRNA of a gene selected from the group consisting of Flt3 ligand, IL-8, MIP-1a and fractalkine or the protein encoded by the gene in the subject method. A composition for preventing or treating pseudoscale glaucoma comprising at least one expression or activity inhibitor selected from the group consisting of Flt3 ligand, IL-8, MIP-1a and fractalkine.

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