CN117323413A - Application of liraglutide in treating diabetes-related eye diseases - Google Patents
Application of liraglutide in treating diabetes-related eye diseases Download PDFInfo
- Publication number
- CN117323413A CN117323413A CN202311151577.8A CN202311151577A CN117323413A CN 117323413 A CN117323413 A CN 117323413A CN 202311151577 A CN202311151577 A CN 202311151577A CN 117323413 A CN117323413 A CN 117323413A
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- Prior art keywords
- liraglutide
- mice
- diabetic
- group
- ocular surface
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- Pending
Links
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Abstract
The invention discloses application of liraglutide in preparing medicines for preventing or treating damage of ocular surface tear functional units of diabetics. Experiments prove that the liraglutide can improve the proliferation activity of the corneal epithelial cells in vitro and reduce the apoptosis of the corneal epithelial cells caused by high sugar. Meanwhile, in a mouse model, the liraglutide eye drops are proved to be beneficial to improving the healing efficiency of the cornea epithelium and promoting the repair of the cornea epithelium nerve fibers. The invention also provides the application of the liraglutide in relieving lacrimal gland fibrosis and inflammatory reaction and increasing the secretion of lacrimal fluid of diabetics, thereby being beneficial to treating the damage of ocular surface related to diabetes and widening the new application of the liraglutide in medicine.
Description
Technical Field
The invention relates to the field of medicine preparation, in particular to application of liraglutide in medicines for treating damage of a functional unit of ocular surface tears of diabetes.
Background
Diabetes is a chronic metabolic disease mainly characterized by long-term blood glucose elevation, and can be complicated with various chronic diseases, such as diabetic nephropathy, diabetic cardiovascular lesions, diabetic bone lesions and the like. More than 50% of patients are counted to have combined damage to the functional units of ocular surface tears. The tear functional unit is composed of cornea, conjunctiva, meibomian gland, lacrimal gland and neural network connecting them, and controls tear film steady state by regulating. Hyperglycemia can cause abnormal functions of cornea nerve structures and dysfunctional tear functional units, and causes hypolacrimation and overevaporation, thereby causing symptoms such as cornea hypoperception, cornea injury healing delay, dry eye and the like, and seriously affecting the vision and life quality of diabetics. Damage to ocular surface tear functional units is critical in the process of diabetes-related ocular surface damage. In terms of mechanism, previous studies have shown that persistent hyperglycemia can induce lacrimal acinus to infiltrate with inflammatory cells, undergo progressive fibrosis, and cause decreased tear secretion. In another aspect, under high glucose conditions, because the tear secretion decreases and tear fluid is in a relatively hypertonic state, increased levels of inflammatory factors such as interleukin-6 (IL-6), IL-8, etc. in tear fluid can disrupt the link between the keratocytes, leading to apoptosis of the keratocytes, further inducing inflammatory cascades, and ultimately leading to diabetes-related ocular surface damage.
At present, the main means for clinically treating the diabetic ocular surface lesions comprise symptomatic treatment such as whole-body blood sugar regulation and local use of artificial tears, but the treatment effect is limited.
Glucagon-like peptide-1 (GLP-1) is a peptide substance secreted by far-end small intestine endocrine cells, and can be combined with specific GLP-1 receptor (Glucagonlike peptide receptor, GLP-1R) on the surface of pancreatic beta cells to promote synthesis and secretion of insulin and exert hypoglycemic effect. Recent studies have found that GLP-1 contributes to improvement of abnormal oxidative stress, inhibition of oxidative stress and inflammation levels, and protection.
Liraglutide (Lira) is a GLP-1 analog produced by gene recombination technology using yeast, and has the chemical name Arg34Lys26- (N- ε - (γ -Glu (N- α -hexadecyl))). The liraglutide has 97% similarity with natural GLP-1, has longer half-life after structural modification, is used for controlling blood sugar of adult type 2 diabetics, and is especially suitable for patients with poor blood sugar control after the maximum tolerable dose of the single metformin or sulfonylurea drug is treated.
At present, no report of liraglutide local application for treating the ocular surface lesions related to diabetes exists.
Disclosure of Invention
The invention aims to provide a novel application of liraglutide in treating damage of functional units of ocular surface tears of diabetes.
The technical scheme for achieving the purpose comprises the following steps.
In a first aspect, the present invention provides the use of liraglutide in the manufacture of a medicament for the prevention or treatment of ocular surface lesions in a diabetic patient, said ocular surface lesions being ocular surface lesions associated with reduced tear secretion.
In a second aspect, the invention provides the use of Li Lila lupeptide in the manufacture of a medicament for preventing or treating damage to ocular surface tear functional units in a diabetic patient.
In a third aspect, the invention provides application of liraglutide in preparing medicines for promoting tear secretion of diabetics
In a fourth aspect, the invention provides the use of liraglutide for the preparation of a medicament for the prevention and treatment of corneal epithelial lesions in diabetic patients.
In some of these embodiments, the use comprises promoting a repair function of the corneal epithelial cells.
In some of these embodiments, the dosage form of the drug prepared with liraglutide is an eye drop.
In some embodiments, the eye drops are: the concentration of the liraglutide in the eye drops is 0.01-3mg/ml, preferably 0.6-1mg/ml.
In some preferred embodiments, the concentration of liraglutide in the eye drops is 0.75-0.85mg/ml.
The beneficial effects of the invention are as follows: the invention discovers the effect of liraglutide on protecting cornea epithelium of diabetics and promoting tear secretion. Based on the discovery, the invention provides application of liraglutide in preparing a novel medicament for treating damage of a functional unit of ocular surface tears of diabetes, and experiments prove that the liraglutide can improve proliferation activity of corneal epithelial cells in vitro and reduce apoptosis of the corneal epithelial cells caused by high sugar. Meanwhile, in a mouse model, the liraglutide eye drops are proved to be beneficial to improving the healing efficiency of the cornea epithelium and promoting the repair of the cornea epithelium nerve fibers. The invention also provides the effect of liraglutide in reducing lacrimal gland fibrosis and inflammatory response and increasing tear secretion of diabetic patients, thereby being helpful for treating diabetes-related ocular surface damage.
The preparation method of the liraglutide eye drops is simple and controllable, and does not need harsh conditions.
Drawings
FIG. 1 is a graph showing the effect of liraglutide on proliferation activity of high-sugar treated human corneal epithelial cells, wherein A is morphological changes of human corneal epithelial cells under light irradiation after 48 hours of treatment with 25mmol/L of normal sugar medium, 50mmol/L and 200mmol/L of high sugar medium and 100nmol/L of liraglutide; b is the statistical result of CCK-8 detection of proliferation activity of human corneal epithelial cells in high sugar culture after 48 hours of liraglutide treatment, P <0.05, P <0.001vs control group, #P <0.05vs HG group (n=3), bar:100 μm.
FIG. 2 is a graph showing the effect of liraglutide on the apoptosis level of high-sugar treated human corneal epithelial cells.
FIG. 3 is a graph comparing healing rates of healthy mice and diabetic mice after corneal epithelial injury, wherein A is a graph photographed under a slit lamp microscope after 3 months of epithelial injury in healthy control mice and diabetic mice; b is the comparison of cornea sensitivity of healthy control mice to diabetic model mice for 3 months P < 0.05P <0.01 (n=3).
Fig. 4 is a graph showing the effect of liraglutide eye drops on promoting healing of corneal epithelial lesions in diabetic mice. FIG. 5 is a graph showing the effect of liraglutide eye drops on promoting the repair of corneal nerves in diabetic mice, wherein A is a panoramic image and a 4X image of immunofluorescence staining of corneal nerve markers beta III-tubulin (red) before epithelial injury in healthy control mice, after epithelial injury in healthy control mice and mice after 3 months of model formation of diabetes, respectively, when liraglutide or physiological saline is used for eye drops for 7 days; b is the statistical analysis result of corneal nerve beta III-tubulin (red) immunofluorescence staining innervation area after the healthy control group mice are not damaged in epithelium and the healthy control group mice and the diabetes modeling mice are damaged in epithelium for 3 months respectively after the eyes are dropped with liraglutide or physiological saline for 7 days. * P <0.05, < P <0.01, < P <0.001 (n=3), UW: unowned, bar:100 μm.
FIG. 6 is a diagram showing that the liraglutide eye drops promote the expression of GLP-1R in lacrimal glands of diabetic mice, wherein A is 20X images of the healthy group, the diabetic control group and the liraglutide experimental group, which are immunofluorescent-stained with GLP-1R (green), the GLP-1R fluorescent signal of the healthy group is stronger than that of the diabetic group, and the GLP-1R fluorescent signal of the liraglutide experimental group is stronger than that of the diabetic control group, bar is 50 μm; b is the result of western blot detection on GLP-1R expression of lacrimal glands of mice in a healthy group, a diabetic control group and a liraglutide experimental group, GAPDH is an internal reference, the GLP-1R expression level of the healthy group is higher than that of the diabetic group, and the GLP-1R expression level of the liraglutide experimental group is higher than that of the diabetic control group, wherein p is less than 0.001 (n=3).
Fig. 7 is a graph showing the effect of liraglutide eye drops on promoting tear secretion in diabetic mice, wherein a is a graph showing the results of detection of tear secretion in mice in healthy, diabetic control and experimental groups, respectively, using phenol red cotton lines, and a statistical graph showing p <0.05, p < 0.0001 (n=5); b is a Masson staining result and a statistical chart of lacrimal gland sections of a healthy group, a diabetic control group and a liraglutide experimental group of mice, and blue color shows collagen fibers, compared with the healthy group, a large amount of collagen fibers are deposited around lacrimal gland blebs of the diabetic mice, and after the treatment of the liraglutide eye drop, the situation of lacrimal gland fibrosis is obviously improved, wherein p is less than 0.01, p is less than 0.0001 (n=5); c is 20X images of immunofluorescent staining of E-cadherin (green) and alpha-SMA (red) of lacrimal glands of mice in a healthy group, a diabetic control group and a liraglutide experimental group, compared with the healthy group, the E-cadherin expression of the diabetic group is reduced, the alpha-SMA expression is increased, the E-cadherin expression of lacrimal acinar cells of the mice treated by the liraglutide is increased, the alpha-SMA expression is reduced, the E-cadherin expression of the lacrimal acinar cells of the mice treated by the liraglutide is reduced, and the Bar is 50 mu m; d is 20X images of immunofluorescence staining of a human lacrimal gland inflammation small body NLRP3 (green) of a healthy group, a diabetic control group and a liraglutide experimental group, the fluorescent signal of the human lacrimal gland inflammation small body NLRP3 of the diabetic group is stronger than that of the healthy group, the fluorescent signal of the human NLRP3 of the liraglutide experimental group is weaker than that of the diabetic control group, which indicates that the lacrimal gland inflammation of the mouse of the diabetic group is heavier than that of the healthy group, and the inflammatory response caused by high sugar can be obviously reduced by the treatment of the liraglutide, and Bar is 50 mu m.
Detailed Description
The present invention will be described more fully hereinafter in order to facilitate an understanding of the present invention. This invention may be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Experimental methods, in which specific conditions are not noted in the examples below, are generally carried out according to conventional conditions, for example, green and Sambrook-s.A.fourth edition, molecular cloning, A.laboratory Manual (Molecular Cloning: A Laboratory Manual), published in 2013, or according to the conditions recommended by the manufacturer. The various chemicals commonly used in the examples are commercially available.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
Example 1 liraglutide increases proliferation activity of corneal epithelial cells and reduces apoptosis in vitro
1. The main reagent comprises:
2. cell line: human corneal epithelial cell line HCE-2 was purchased from ATCC company under the designation HCE2[50.B1 ]](CRL11135 TM )
3. Cell culture and pharmaceutical formulation
Human corneal epithelial cell line HCE-2 was cultured at 37℃with 5% CO 2 Is passaged when the cells are fused to 70% -80%.
9.0g of glucose powder is weighed, the volume is fixed to 50ml by ultrapure water sterilized at high temperature and high pressure, 1mol/L glucose solution is prepared, and the glucose solution is filtered and sterilized by a 0.22 mu m filter membrane and stored at 4 ℃ for standby.
The liraglutide injection (6 mg/ml) is diluted to 100 mu mol/L by ultrapure water sterilized at high temperature and high pressure, and is stored at-20 ℃ for standby after split charging.
4. Experimental results-influence of liraglutide on proliferation activity of high sugar-treated human corneal epithelial cells
As shown in FIG. 1, the photomicrographs of the corneal epithelium revealed that the morphology of human corneal epithelium was changed in 50mmol/L and 200mmol/L high sugar culture, the number of living cells was decreased to various degrees, and the intercellular spaces were increased. Thus, CCK-8 results indicate that liraglutide can significantly improve the decrease in proliferation activity of human corneal epithelial cells due to high sugar culture.
5. Experimental results-influence of liraglutide on apoptosis level of high sugar treated human corneal epithelial cells
Flow cytometry examined apoptosis levels of human corneal epithelial cells at various concentrations of glucose and after 48 hours of liraglutide treatment. Apoptosis was analyzed using the BD Annexin V-FITC apoptosis detection kit. As shown in fig. 2 (P <0.05, n=3), the overall apoptosis rate of human corneal epithelial cells in 50mmol/L and 200mmol/L high sugar culture was significantly increased compared to human corneal epithelial cells in normal sugar culture, especially with early apoptosis being more pronounced, the overall apoptosis rate of human corneal epithelial cells was decreased after the addition of liraglutide, suggesting that it can inhibit apoptosis of human corneal epithelial cells caused by high sugar.
Example 2 liraglutide eye drops promote repair of corneal epithelium and nerves in diabetic mice
The mouse model used in this example was a 5 week old male C57BL/6J mouse, purchased from Jiangsu Ji-kang biotechnology Co., ltd, and the experimental mice were fed on a normal diet and were free to eat and drink water. The room temperature in the laboratory is 18-25 ℃, the relative humidity is 40-60%, and 12 hours of illumination are alternated.
1. Modeling method
After C57BL/6J mice are adaptively fed for 1 week, the mice are randomly divided into a control group and a diabetes group, the diabetes group mice are continuously injected with 50mg/kg/d of streptozotocin for 5 days to establish a diabetes model, the fasting blood glucose of the mice is monitored after the last injection, and when the continuous 3 fasting blood glucose levels are higher than 16.7mmol/L, the modeling is considered to be successful. The control group was given sodium citrate buffer for intraperitoneal injection. When the diabetic mice are 3 months in the disease course, corneal epithelium is scraped off, and a corneal epithelium damage model is established.
2. Experimental group (10 per group)
Health group (Ctrl): healthy mice, without intervention.
Diabetes group (DM): diabetic mice, without intervention.
Healthy control group (ctrl+nacl): after scraping the epithelium, the healthy mice drop eyes with physiological salt, 5 mu l each time, and 5 times daily for 7 days;
liraglutide control group (ctrl+lira): after scraping the epithelium, the healthy mice drop eyes with 0.8mg/ml liraglutide, 5 mu l each time, and 5 times daily for 7 days;
diabetes control group (dm+nacl): after scraping the epithelium, the diabetic mice drop eyes with physiological salt, 5 mu l each time, 5 times daily for 7 days;
liraglutide experimental group (dm+lira): diabetic mice were then instilled with 0.8mg/ml liraglutide eye drop, 5 μl each time, 5 times daily for 7 days.
3. Pharmaceutical formulation
Preparation of streptozotocin: fresh citrate buffer is prepared on the same day, and corresponding doses of streptozotocin are weighed, dissolved in ice in a dark place, and the prepared streptozotocin solution is injected within 20 minutes.
Preparing liraglutide eye drops: liraglutide injection (6 mg/ml) was diluted to 0.8mg/ml in 0.9% NaCl physiological saline solution and the eye was spotted at a dose of 5 μl each time, 5 times daily.
4. Experimental results-liraglutide eye drops for promoting healing of corneal epithelial injury of diabetic mice
Fluorescein sodium staining was performed and photographed 0h, 12h, 24h, 36h, 48h after scraping the mouse corneal epithelium, respectively, and changes in corneal epithelial defect area were measured by ImageJ to reflect the rate of epithelial healing.
After modeling corneal epithelial damage for each group of mice, epithelium was completely absent in the region of 2mm diameter at the center of the cornea, and sodium fluorescein staining showed green fluorescence. Healthy control mice had faster healing rates of corneal epithelium after corneal epithelium curettage, and had healed completely until 36 hours, with no fluorescence seen with sodium fluorescein staining. Compared with the diabetic mice induced by streptozotocin, the healing speed of the cornea epithelium is obviously reduced, and fluorescein sodium staining is carried out at the same time after the epithelium is scraped, so that the staining area of the epithelium of the diabetic mice is obviously higher than that of the mice in a control group, and the cornea epithelium of the diabetic mice is obviously damaged, and the normal repair function of the cornea epithelial cells is influenced by diabetes (see figure 3).
After epithelial injury of healthy control mice and diabetic model-making mice for 3 months, corneal epithelial sodium staining photographic images and ImageJ statistical analysis of the results of corneal sodium staining areas of mice in each group are carried out by using liraglutide or physiological saline respectively after eye drops for 7 days.
The staining of fluorescein sodium was still visible 48 hours after the corneal epithelium of the diabetic mice was scraped off, and was seen in comparison with the liraglutide eye drops and the normal saline eye drops (see fig. 4, P <0.05, n=3), which showed less staining than the normal saline eye drops, suggesting that the liraglutide eye drops can significantly improve the corneal epithelium healing efficiency.
5. Experimental results-liraglutide eye drops for promoting cornea nerve repair of diabetic mice
After each group of mice was scraped and watered with liraglutide or physiological salt for 7 days, the cornea was harvested and plated for fluorescent staining. The results of fig. 5 show that compared to mice with intact epithelium, the density of the corneal subepithelial nerve fibers was significantly reduced in mice with scraped corneal epithelium, and in addition, compared with saline water drops, liraglutide drops can increase the density of subepithelial nerve fibers to help promote repair of subepithelial nerve fibers in healthy control group or diabetic group mice.
Example 3 liraglutide promotes tear secretion in diabetic mice
1. Modeling method
The diabetes modeling method and related solution formulation method used in this example were the same as example 2, with intervention at 3 months of diabetes.
2. Experimental group (10 per group)
Health group (Ctrl): healthy mice, without intervention
Diabetes group (DM): diabetic mice, without intervention
Diabetes control group (dm+nacl): diabetic mice were instilled with physiological saline 5 μl each time, 5 times daily for 14 days;
liraglutide experimental group (dm+lira): diabetic mice were eye-dropped with 0.8mg/ml liraglutide eye drop for 14 days with 5 μl each time, 5 total eye drops each day.
3. Experimental results-liraglutide eye drops restoring expression of GLP-1R in lacrimal gland of diabetic mice
The lacrimal glands of mice in healthy and diabetic groups, each having GLP-1R expression and the diabetic group having weaker expression than the healthy group, were frozen and the sections were immunofluorescent stained (fig. 6A). Two groups of mice are taken to extract proteins from lacrimal glands and measure protein concentration, GLP-1R expression is detected by adopting western blot, firstly, separating gel and concentrated gel are prepared, the separating gel and the concentrated gel are placed into an electrophoresis tank, electrophoresis liquid is filled into the electrophoresis tank, each group is mixed with 30 mug of proteins and loading buffer for boiling and loading for electrophoresis, then PVDF membrane is used for membrane transfer, then the membrane is put into quick sealing liquid for sealing for 10 minutes, after TBST is washed for three times, the PVDF membrane is incubated overnight at 4 ℃ in GLP-1R primary antibody. The next day the membrane was washed three times with TBST, the secondary antibody was added and incubated for 2 hours at room temperature on a shaker, and then washed three times with TBST, finally the membrane was added dropwise with developing solution and exposed in a gel imaging system, and the picture was saved. The results are consistent with immunofluorescence staining, the lacrimal glands of the mice in the healthy group and the diabetic group have GLP-1R expression, and the imaging J measurement results show (shown in fig. 6B) that the GLP-1R protein band density of the diabetic group is lower than that of the mice in the healthy group, and the difference has statistical significance, namely, the expression level of the lacrimal glands of the mice in the diabetic group is lower than that of the mice in the healthy group. This suggests that diabetes inhibits GLP-1R expression in the mouse lacrimal gland. We found that liraglutide, as an agonist of GLP-1R, was able to restore high glucose-induced downregulation of GLP-1R expression in the lacrimal glands (FIGS. 6A, B).
4. Experimental results-liraglutide eye drops for reducing lacrimal gland fibrosis and inflammatory reaction and promoting tear secretion of diabetic mice
The tear secretion of each group of mice was measured using phenol red cotton, respectively, by pinching the phenol red cotton with forceps and placing it in the conjunctival sac of the lower eyelid at a distance of about 1/3 from the outer canthus for 60 seconds. The length of the tear line was measured with a vernier caliper, analyzed using the average of both eyes, and the results were counted with ImageJ. Fig. 7 shows that the average infiltration length of diabetic mice is about 5mm, the average infiltration length of healthy mice is 14mm, and tear of diabetic mice is significantly lower than that of healthy mice, i.e. dry eye manifestation occurs. In contrast, the amount of tear secretion of diabetic mice after the treatment with liraglutide eye drops increased, and the average infiltration length was about 7mm, which was higher than that of the physiological saline-treated group (fig. 7A). The Masson staining results of the mouse lacrimal gland sections suggested that liraglutide eye drops can significantly reduce collagen fiber deposition between lacrimal gland acinar cells caused by diabetes (fig. 7B).
In addition, studies have found that increased E-cadherin expression and decreased alpha-SMA expression in lacrimal acinar cells of mice following treatment with liraglutide suggests that liraglutide can reduce epithelial-to-mesenchymal transition of lacrimal acinar cells (FIG. 7C). We further explored the expression of NLRP3 inflammatory bodies, and the immunofluorescence results suggested that the diabetes group NLRP3 fluorescent signal was stronger than that of the healthy group, whereas the liraglutide experimental group NLRP3 fluorescent signal was weaker than that of the diabetes control group, indicating that the tear gland inflammatory response of the mice in the diabetes group was heavier than that of the healthy control group, and that the liraglutide treatment significantly reduced the inflammatory response caused by high sugar (fig. 7D). Taken together, these results suggest that liraglutide eye drops can promote tear secretion in diabetic mice by reducing lacrimal gland fibrosis and inflammatory response, thereby reducing ocular surface damage caused by diabetes.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (9)
1. Use of liraglutide in the manufacture of a medicament for preventing or treating ocular surface lesions in a diabetic patient, said ocular surface lesions being ocular surface lesions associated with reduced tear secretion.
2. Use of liraglutide in the preparation of a medicament for preventing or treating damage to ocular surface tear functional units in a diabetic patient.
3. Use of liraglutide in the preparation of a medicament for promoting tear secretion in a diabetic patient.
4. Use of liraglutide for the preparation of a medicament for the prevention and treatment of corneal epithelial lesions in diabetic patients.
5. The use of claim 4, wherein the use comprises promoting repair of corneal epithelial cells.
6. The use according to any one of claims 1-5, wherein the pharmaceutical formulation prepared with liraglutide is an eye drop.
7. The use according to claim 6, wherein the concentration of liraglutide in the eye drops is 0.01-3mg/ml.
8. The use according to claim 7, wherein the concentration of liraglutide in the eye drops is 0.75-0.85mg/m l.
9. The use according to any one of claims 1-5, wherein the dosage form of liraglutide is artificial tears, eye patches, injection.
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