WO2019054960A2

WO2019054960A2 - Improving ophthalmic telomerase activity via topical and local ocular applications and preventing, delaying and / or treating impairments or diseases experienced due to degenerative processes (such as aging)

Info

Publication number: WO2019054960A2
Application number: PCT/TR2017/050593
Authority: WO
Inventors: Iskender Alkin SOLMAZ; Isilay KAVADARLI; Murat Kubilay TURKMEN
Original assignee: Solmaz Iskender Alkin; Kavadarli Isilay; Turkmen Murat Kubilay
Priority date: 2016-11-28
Filing date: 2017-11-23
Publication date: 2019-03-21
Also published as: WO2019054960A3; TR201617350A2

Abstract

The method subject to the invention includes administering natural or synthetic (obtained in laboratory) active ingredients that will activate telomerase enzyme described herein so that the active ingredients will have rapid and high bioavailability on the targeted tissue. Thanks to administration of the active ingredient activating telomerase enzyme activity subject to the invention in drop form, pomade form, gel form, sub-tenon injection, subconjunctival injection, subconjunctival extended release (short or long term), anterior chamber injection, posterior chamber (intravitreal) injection, intravitreal extended release (short or long term), peribulbar or retrobulbar injection form into the eye; impacts of aging on tear film, conjunctiva, sclera, cornea, trabecular meshwork, iris, pupil, lens, blood vessels feeding the eye, choroid, ciliary body, retina and optic nerves can be delayed, stopped or improved.

Description

IMPROVING OPHTHALMIC TELOMERASE ACTIVITY via TOPICAL AND LOCAL OCULAR APPLICATIONS AND PREVENTING, DELAYING AND / OR TREATING IMPAIRMENTS OR DISEASES EXPERIENCED DUE TO-DEGENERATIVE

PROCESSES (SUCH AS AGING)

Technical Field

The invention is related to an ophthalmic administration method of active ingredients - which can be natural or synthetic (obtained in a laboratory) compound - activating telomerase enzyme that is developed for preventing or treating age-related ophthalmic diseases.

State of the art

Eye is a large-marble size spheroidal organ that is located in the eye socket and that enables us to see. Eye is a combination of three layers known as sclerotic coat that is capable of reflecting and refracting light, vascular layer and nerve cell layer. The sclerotic coat is the outermost layer and made up of connective tissue. It includes the transparent layer (cornea) that resembles clear watch crystal and while hard layer (sclera). The transparent layer has refraction power of 43 diopters. Tears, aqueous humor and leaks from veins around it feed the cornea. If this layer loses its transparency, eye will not be able to see the objects. It will only make out light and movements. The sclerotic coat (sclera) is white and it is covered with a smooth and venous mucosa (conjunctiva), similar to an onionskin, on the front side. There is a vascular layer in the sclerotic coat. It has plenty of blood vessels. These help to feed the eye. The vascular layer has three sections; choroid that takes up most of the space in the back, ciliary body that is located between choroid and iris, contains ciliary muscle assuring harmony and holds intraocular lens and iris that gives the eye its color and functions as the diaphragm of eye. The gap in the middle of iris is known as pupil (pupilla). The nerve cell layer is the core layer of eyes and this layer enables us to see. It has two types of sensitive cells: cones and rods. An eye has 5 million cones and 120 million rods. Cones enable us to see during the day as well as seeing colors and patterns, and rods allow us to see at dawn and around us. Astigmatism, myopia, hypermetropia, presbyopia, hordeolum, glaucoma, amblyopia, cataract, diplopia, nyctalopia, eye pain red eye, eye allergies, xerophthalmia, tearing, swollen eyelid and age-related macular degeneration are the examples of common ophthalmic diseases.

Eye is one of the sensory organs that start to experience early signs of aging process. There might be some natural age-related changes having impact on the eyesight but serious illnesses experienced more frequently due to the aging process might also have impact on the eyes. Regular ophthalmologic examinations are very important at older ages; there are several eye diseases that start without any symptoms at the beginning but the damage they cause might be minimized in case of early diagnosis. Pupil gets smaller and its respond to light weakens with age. Consequently, people have difficulties in seeing in the dim light and delayed darkness-light adaptation. The crystalline lens starts to lose its flexibility. As a result, age related sightedness starts. This is known as presbyopia. Presbyopia is experienced by people above the age of 40. The signal received by the brain when a faraway object comes closer is assessed and then transmitted to the eye. When muscles in the eye's ciliary body are contracted and relaxed, the connected fibers are tensioned or released. These fiber movements thicken and thin the lens and have impact on changing the refraction capacity. Eyes lose this capability with age. This is considered as a physiological aging, not as pathological condition. It can be rehabilitated with glasses and contact lenses and there are surgical treatment options for cornea, lens and sclera. The eye lens is normally transparent but it starts to turn yellow with the age. This process reduces light transmission capacity of the lens, increases light scattering and increases the blue light absorbed by the lens. Consequently, color perception and contrast sensitivity skills are decreased.

Dry eye also known as keratoconjunctivitis sicca (KKS), might occur with age and it is experienced with volume or function of tear is insufficient. Tear hyperosmolarity is one of the key mechanisms of the disease and it has material role in epithelial cell damage. Keratoconjunctivitis sicca is classified as related to aqueous layer failure (Sjogren Syndrome and Non-Sjogren) and evaporative (meibomain glands disease, exposure, insufficient blinking, related to contact lens, related to environmental factors). The most common reason of non-Sjogren KKS is hyposecretion related to primer age. Neurological lesions experienced as a result of sensory and motor reflex loss increasing with age are another reason. The weight and thickness of lens increase with age but its adaptation capacity decreases. The new cortical fiber layers formed around it stress and thicken the lens core. Protein clumps with high molecular weight are created as a result of chemical change and proteolytic dissociation of crystalline (lens proteins). This clumping might be as severe as causing intense fluctuations on the lens's sectional refraction index and related light scattering and reduced transparency. Chemical change of lens core proteins increase the pigmentation and this causes the increased yellow or brown spotting on the lens with age. Glutathione on lens cytoplasm and decrease in potassium concentrations as well as increase in sodium and calcium concentrations are other age related changes. Multifactorial age related cataract is one of most common reasons of visual impairment experienced at older ages. The most important reason of central vision losses experienced by USA people over the age of 50 on one eye or both eyes is age related macular degeneration. Prevalence of disease is roughly 85 to 90 % for dry type and 10 to 15 % for neovascular type. Natural aging process causes changes on the macula that can not be always determined clinically and that have impact on outer retina, retina pigment epithelium (RPE), bruch membrane and choriocapillaries. Glaucoma is a type of disease that is characterized with high levels of intraocular pressure having negative impact on the normal functions of optic nerve head. The two primary types of glaucoma are congenital and acquired glaucoma. Besides, acquired glaucoma is classified as open angle and closed angle glaucoma. Family history is important in both types. 2 % of people over the age of 40 and 10 % of people over the age of 80 suffer from acquired glaucoma all around the world. Patients suffering from primer open angle glaucoma generally remain asymptomatic until significant loss of visual field is experienced. Patients suffering from high intraocular pressure might rarely complain from symptoms such as eye pain, headache and seeing halos around light. Symptoms of primer open angle are increased intraocular pressure (intraocular pressure > 21 mmHg), optic disc changes and glaucomatous visual field changes. Compounds activating synthetic telomerase enzyme are developed for slowing down aging process of humans and minimizing age related symptoms. Telomere is a special heterochromatin structure that is on the edges of eukaryotic linear chromosomes and that does not code any genes. Existence of telomeres protects chromosome edges from random double chain DNA fragmentation and thus avoids uncalled for joining of chromosome edges or nucleotide fragmentation of chromosome. Besides this physical protection of chromosomes, eukaryotic telomeres have important cellular functions such as chromatin organization, chromosome replication and cell reproduction. Mammalian telomeres might have 1 -50 kb telomere DNA depending on type of living creature, cell type and genetic history. Human telomeres are 10-15 kb in reproductive cells but it is shorter in some somatic cells and generally in cancer cells. These end series are well protected. Human telomeres are made up of 3' TTAGGG hexanucleotid series that are at the end of chromosomes and double strand, repeated one after another. These hexanucleotid series end with T-loop 100-00 nucleotide Guanine rich (G-tail) overhanging 3' single stand TTAGGG series. T-loop pattern unique to telomeres is created when telomeres coil up on themselves. Single strand overhanging Guanine rick single strand (G-tail) goes "inside" the double strand telomere. This structure replaces one of the telomere strands and creates the second loop, namely d-loop. These t-loop and d-loop structures protects telomere from end-to-end joining with other chromosomes and cell cycle control points starting telomere repair by detecting telomeres as chromosome fractures. Telomeres are averagely reduced by 50 to 150 base pairs in each cell division (replication). This telomere shortening eventually restricts the number of cell division. Recent observations have confirmed that regulation of telomeres is an important factor in cell cycle of several eukaryotic cells. Telomere joining leads to formation of dicentric chromosomes fractured during mitosis and causes chromosome bridges, fractures and joining. Ultimately, the genomes of surviving cells go through changes. Nonfunctional chromosome ends and genome imbalances also cause changes on the telomere length. This leads to accelerated or delayed control of cell aging. Hence, the excessively shortened telomeres cause loss, reorganization of genetic information or loss of its balance. These genomic changes, eventually, lead to both cancer and aging of cell phenotype. Telomeres in reproductive cells, lymphocytes displaying clonal development and immortal cancer cells should be preserved for assuring continued cell division. The most common method assuring protection of telomere length is producing telomeres as novo and increasing telomerase activity in cells for closing telomere.

There have been several studies on using telomeres for treating diseases. Although majority of these studies focuses on life threatening diseases such as cancer, there are several applications and studies related to cosmetics sector. One of these studies is the invention subject to the patent numbered 2015/03756 and titled "Gemcitabine and combined telomeres inhibitor for cancer treatment". A method and kit for preventing proliferation of cancer cells is described in connection with one gemcitabine and one telomerase inhibitor combination. When used for cancer therapy, two compounds used in combination improve efficiency of anti-cancer treatment achieved by solely using Gemcitabine or solely using telomerase inhibitor. Preferably, efficiency is supra additive or synergistic in the nature depending on the combined effects of separate agents by minimum exacerbation of side effects. Another study is the invention subject to the patent numbered EP 1592435 A1 and titled Ophthalmic formulation for the prevention and treatment of ocular conditions". The invention subject to the patent mentioned herein is a compound developed for treating and preventing age related eye diseases and impairments. The compound is also helpful prevention and treatment of other negative eye conditions related to oxidative and / or free radical damage in eyes; these conditions might be a condition, disease or impairment on cornea, retina, lens, sclera, anterior segment or posterior segment of the eye. The abovementioned compound contains an ophthalmic penetration enhancer such as minimum 0.6 % biocompatible chelating agent methylsulfonylmethane (MSM).

Another study is the invention subject to the patent numbered WO 2015100269 and titled "Compositions and methods for providing active telomerase to cells in vivo". This invention assures liposomes for giving nucleic acids in order to express telomerase reverse transcriptase and / or telomerase RNA component to targeted cells of a subject. Expression of active telomerase might increase length of telomeres in cell. Such type of extension is helpful for people suffering from diseases related to shortened telomere. In conclusion, the need for a method developed directly applying a compound to the eyes for improving telomerase activity required for treatment and prevention of age related eye diseases, which will eliminate the disadvantages of the available technique, and the insufficiency of existing solutions necessitated making an improvement in the technical field.

Short Description of the Invention

This invention is about an application method that meets the abovementioned requirements, eliminates the disadvantages and introduces some additional advantages and it allows directly applying an active component to the eyes in a compound format pharmacologically suitable for the active ingredient, such as ophthalmic pomade, gel, injection and / or drop, so that the active component increasing telomerase enzyme activation can be administrated for treatment and prevention of age related eye diseases.

The purpose of invention based on the state of the art is to delay, stop and / or heal age related eye diseases since the designed compound to be administrated activates the telomerase enzyme and through restoration of telomeres shortened with age.

The purpose of invention is to apply the active ingredient improving telomerase enzyme activity to the eye in drop form, pomade form, gel form, sub-tenon injection, subconjunctival injection, subconjunctival extended release (short or long term), anterior chamber injection, posterior chamber (intravitreal) injection, intravitreal extended release (short or long term), peribulbar or retrobulbar injection form and thus to use applications offering target oriented, high bioavailability on effected areas for treatment of different diseases.

Structural and characteristics of the invention and all its advantages shall be more clearly understood thanks to the following detailed explanations and thus the assessment should be made by taking into consideration these detailed descriptions.

Detailed Description of the Invention

This detailed description explains the active ingredient improving activation of telomerase enzyme that is subject to the invention designed for treating age related eye diseases and preventing these diseases through cell rejuvenation and administration method of this active ingredient; this description is provided only for explaining the subject in detail and it shall not impair generality of it in any way.

Aging is a constant and foreseeable process that includes growth and development of a living organism. Aging is inevitable but aging rate varies from person to person. Our aging process depends on our genes, environmental factors and lifestyle. Aging gradually reduces organ functions and body systems. These changes might be noticed only in case of times requiring effort or under stress. A person's time to respond to stimulants increases with age. A longer recovery time might be required after an illness. Age related changes in our body make us more sensitive to several diseases and to side effects and complications of medical treatment administered. The response time of body slows down with age and thus a person might need more time to adapt to the environmental changes.

The aging rate is under the influence of several factors due to the superficial reasons of the world we live in. Besides stress, smoking, life quality, nutrition habits, lack of exercise, there seems to be some important and primary causes of aging. The most superficial of those is changes related to endocrine system. The reduction of hormones and related loss of function are considered as the most important causes of aging. However, this is considered as an outcome of underlying causes rather than being considered a reason on its own. This underlying cause changes the mechanism of endocrine system and this leads to problems. In a sense, the endocrine system is the cause and outcome of this cycle. Free radicals are reactive products, in other words they are released after a reaction. These can be naturally produced by the body or taken externally. Although oxygen is crucial for human life, some reactive types of oxygen might be dangerous and these side products might react and damage DNA, proteins, lipids and carbohydrates. When DNA is damaged, cancer occurs if restoration and protection mechanisms are insufficient. Free radicals are released when an atom having coupled electrons on its outer orbital loses its electron. High energy and instable free radicals having uncoupled electron tend to have reactions that might cause cell damage. Direct or indirect damages of free radicals cause rapid shortening of telomeres and cell aging. It is also observed that free radicals have vital role in cell signalization and killing bacteria. This process has advantages and disadvantages. Mechanisms that will restore and minimize damage of free radicals emerged within the evolutionary process. The key element of aging is telomeres. Telomeres are seen on the ends of eukaryotic chromosomes. These highly critical elements are important for non-coding cell division and DNA restoration. They are from after long repetitions. Losses and shortenings might be experienced during DNA replication. The protective particles, namely telomeres, are shortened during these replication processes and thus DNA code is protected. This allows preserving the genetic information. Shortening of telomere means reduced DNA efficiency. Reduced restoration activity increased cancer risk. On the other hand, telomere shortening stops cell division at a certain point. A body that does not renew itself heads to destruction. This starts to impair overall body efficiency. Telomerase enzyme is the key element here. Thanks to telomerase enzyme, telomeres are added to shortened telomeres. This unveiled expectations related to immortality. Today, it is (partially) possible to unveil facts about human lives based on length of telomeres. Our bodies have three types of cells: stem cells, germ cells (also known as reproductive cells and they are sperms in male body and eggs in female body) and somatic cells that make up 99.9 % of our entire body. The first two cell groups never age because they are almost capable of producing unlimited telomerase enzyme. Thus, they never lose their functionality. These two cell types will be much more important in medicine in the following years since they do not age. However, telomerase enzyme of somatic cells, which make up 99.9 % of a body, is blocked and thus somatic cells age gradually and cause bodily aging. DNA of somatic cells and DNA information of other two cell types is identical. However, one group has unlimited level of telomerase expression but somatic cells have no telomerase expression since the related receptor is blocked. When the blockage on the above-written blocked receptor is released through compounds enhancing telomerase enzyme production, somatic cells can be rejuvenated and become functional and they even not aged a bit under laboratory conditions. This promises immortality or >200 years healthy life under laboratory conditions although it has not been proved in human body, yet. On the other hand, in 201 1 , a group of scientists from Harvard published their study on Nature; rats were artificially aged and then restored to a young and healthy profile by restoring their telomeres in this study and the rats lived 40 % longer. Telomeres are heterochromatic zones that do not contain genetic information and they are made up of special DNA tandem repeats. Telomere DNA strands are different from other DNA strands in terms of structure and function and they have a primary biological function. They take part in completing the last section of linear chromosomal DNA molecule during replication. It protects the last section of chromosome against abnormal conditions such as recombination, destruction and fusion. It assures chromosome integrity and stability. DNA end freed due to lack of functional telomere will not be stable and random restoration of DNA breaks leads to impaired cell functions. Broken chromosomes are cut by nucleases and these ends are joined randomly. Thanks to the proteins attached to telomeres, telomeres assure stability and telomere end is not detected as chromosome break. Telomere DNA is made up of simple tandem repeats rich in CA and GT. Although telomere structure is primarily the same on different organisms, there are differences in length and tandem repeats. A strand of telomere DNA is characterized by containing G clumps. This section is divided into sub telomere and telomere zones. All species have sub telomere and telomere zones; they are made up of different strands and they form the natural structure of chromosome end. The sub telomere section of human chromosome end is on the section adjacent to chromosomes (proximal) and the main telomere section follows this. The length of sub telomere section is variable and DNA repeats are heterogeneous. The main telomere section following the sub telomere section continues initially as double stranded and then single stranded. The length and DNA repeats are specified to types but each type has homogenous DNA repeats. Telomere structure of all eukaryotes is preserved. Normally, the ordinary primary telomere length is regulated by telomerase enzyme and various proteins connected to telomere. However, functions, structures and types of these proteins have not been clearly identified, yet.

So far, examined organisms have revealed various proteins functioning by connecting to telomere double and single strands. Some of these proteins wrap single and double strands end of telomere and help T-loop formation to protect telomere from destruction. Some make sure that telomerase enzyme is connected or not connected to telomere and thus control length of telomere. Although structure and functions of all these proteins are primarily the same, there are different types. Proteins can be examined as single and double stranded proteins. Thus, the primary function of telomeres is to connect G end on T-loop to D-loop. This prevents telomere t-loop from merging with other breaks on the chromosome. T-loops also directly or indirectly help stabilizing chromosome telomere. When telomere DNA is damaged, DNA damage mechanisms ruin G3' single strand and chromosomes are joined end to end. Thus, blocking recognition by this control point is sufficient to assure stability of chromosome ends. The second important function of telomeres is to make sure telomerase enzyme penetrates into telomere and to preserve single stranded length of telomere. D-loop section in base pair with T-loop should be separated for assuring telomerase penetration. Thus, a helicase separates T-loop from D-loop section for assuring telomerase penetration. In other words, when telomere G3' single strand is to extend on young cells, T-loop is released with the help of helicase enzyme and transformed into single strand. New repeats are added to G3' ends by telomerase enzyme. When the adding process is completed, G3' single strand end reforms D-loop connection for protecting telomere. This protects the extended T-loop telomere.

Telomerase is a reverse transcriptase having a ribonucleoprotein structure that catalyzes adding telomere repeats to telomeres of eukaryotic chromosomes and it is a large enzyme complex. The first person who discovered the activity in telomere synthesis highlighted the healing function of chromosome ends on special corn tissues. Telomerase represents a unique enzyme that can synthesize telomere DNA. It is argued that telomerase extension activity treated with ribonuclease A functions as a mold for telomere addition of integral RNA component. This is supported with discovery of Tetrahymena telomerase RNA. In vitro telomerase extension trials is the key step of defining telomerase activity in several different organisms containing other ciliatas, humans, rats, yeast, frogs and plants. The first time telomerase activity was noticed in humans was on HeLa, the cervical cancer cell line. Furthermore, it was observed in fetal, newborn and adult testis and ovaries. However, it was not observed in spermatozoa and testis of elderly people. Higher telomerase activity is observed on human fetal tissues and newborn peripheral blood cells. In adults, telomerase activity in mononuclear peripheral blood cells is lower when compared to tumor cells and it is lower in elders when compared to children. Besides, telomerase activity of people over the age of 19 is reduced. The newborn telomeres seen due to telomerase activity in leukocytes are longer when compared to adults. Telomerase activity is not observed on several human somatic tissues. It is generally seen on tissues having high replicative capacity.

Ordinary mammalian somatic cells can be divided under in vitro conditions to a certain number. This maximum number of division is known as "Hayflick Limit". Proliferation limit is also known as "mitotic clock". Replicative aging depends on total number of cell division but it does not depend on chronological or metabolic timing. It is indicated that all chromosome ends are reduced because of DNA replication, they can be divided in a certain number and the cell starts to die after the critical reduction point. There is a constant telomerase activity in germ-line cells. Thus, germ-line cells might have mutation but they do not age. In case of multicellular animal evolution, systematic aging of non- germ-line (somatic) cells has a selective advantage. Necrosis and regular growth occur according to rules and cancer risk is reduced. On the other hand, aging in organisms can be defined in different forms. These definitions discuss aging within specific scopes. Aging covers the entire chain of events that are regulated with a genetic system and that leads organism to death through structural and functional changes. If it is examined generally, we can say that aging and necrosis of human cells occur in two steps. M1 step emerges because of significant shortening of telomere single strand. The cell division stops and aging starts when this shortening process reaches to a critical point. If telomere length can be preserved at this point, the cell survives as an aged cell. Cyclin Dependent Kinase (CDK) is prevented and the transition of the cell from GO or G1 to S phase is stopped. Thus, the cell is not divided and it ages. There are different factors triggering (stimulating) the aging schedule. Telomere shortening is the most well defined physiological stimulator for the aging system. The central role of this event is established in terms of aging process. Modified DNA metabolism defines several diseases such as early aging. Enzymes triggered by such diseases interfere on various stages of DNA metabolism or repair. These diseases bring along early aging in the future. Expression of activated oncogenes also starts aging. Aging works as a type of tumor repressor system. Although it is not entirely clear how DNA damages trigger the molecular mechanism of aging, it can be said that such diseases have impact on telomere length and function. M2 step; this step involves cells surviving M1 step. A cell will survive M1 step and go to M2 step when proteins similar to p53 and Rb in the cells waiting on M1 step are impaired by viral oncoproteins (by using viral oncogenes). Thus, the cell cycle skips from G2 to S phase because these proteins cannot function on G1 step and cell division continues. However, telomerase enzyme activity in soma cell is significantly reduced, scarcely any, in that case and thus telomere length is gradually reduced. Cells die on M2 point if telomere length is excessively shortened. If a cell's telomere length remains stable on M2 point, it will survive M2 point; it will be immortal and cell division will continue. This process emerges because of telomerase enzyme regulation or reactivation. Cancer cells are types of cells that pass M2 step. Telomere shortening leads replicative aging in primer human cells. Control points depend on p53 and Rb proteins. P53/Rb inhibition allows cell division but then the cell goes into "telomere crisis". Chromosome structure is impaired during this period and necrosis takes place. Cell size cannot be controlled due to p53 loss. Telomere function is interrupted and the cell is dragged to micro chaos. At this stage, any second genetic change occurring on the cell will either lead to necrosis or cause cellular change. Genetic chaos is the most crucial step in development of several cancer types in humans. Telomere crisis starts replicative aging. Telomerase expression allows surviving replicative aging or telomere crisis and assures immortality. In short, telomerase is active on certain stages of gametogenesis and telomere length is passed onto from one generation to another in stem cells. Telomerase will be repressed throughout generations of continued differentiation. This is particularly shown in cultured human fibroblasts. If division of somatic cells continues, losses on telomere DNA ends continue. Checkpoints in cell cycle manage the cell cycle. When reduction in telomere length reaches a critical point, the cell cycle activates Hayflick Limit and cell division stops. Hayflick limit can be skipped through mutations or viral oncogene expression. A cell can be immortal starting from the first moment; it reaches immortality via telomerase activation after several divisions, during crisis or at a stage close to start of crisis. Telomerase activity occurs when TTAGGG repeats are added to the ends of normal human chromosomes. It is observed that artificial telomere addition to cells lead to significant increases in growth potential. Trials using primer human cells confirmed that aging is observed following a certain number of cell division but telomerase positive cells do not suffer from aging and division continues. Some cell lines were examined along population after ordinary aging points and it was observed that they did not only continue to grow but also showed normal karyotype and a young morphology. Tests conducted on three different types of cells, namely retina pigment epithelium cells, fibroblasts and vascular endothelium cells also achieved similar conclusions and the tests confirmed that telomere shortening have a universal role in limiting length of life in human cells.

The study conducted by taking into consideration the impacts of telomere on aging has revealed that telomerase enzyme can be used for preventing cell aging in case of age related eye diseases and abnormalities. The method subject to the invention includes target-specific administration of a natural or synthetic (produced in a laboratory) that will enhance telomerase enzyme activity mentioned herein. Thanks to administration of the active ingredient improving telomerase enzyme activity subject to the invention in drop form, pomade form, gel form, sub-tenon injection, subconjuctival injection, subconjuctival extended release (short or long term), anterior chamber injection, posterior chamber (intravitreal) injection, intravitreal extended release (short or long term), peribulbar or retrobulbar injection form into the eye; impacts of aging on tear film, conjunctiva, sclera, cornea, trabecular meshwork, iris, pupil, lens, blood vessels feeding the eye, choroid, ciliary body, retina and optic nerves can be delayed, stopped or improved. This allows delaying, stopping and / or healing age related eye conditions or diseases such as dry eye, arcus senilis, loss of near vision (presbyopia), iris atrophy, loss of pupil reactions, cataract, glaucoma, age related damages on nerve layer (AMD etc.) and optical nerve atrophy.

The developed active ingredient that enhances telomerase enzyme activity can be used for treatment of eye diseases caused by oxidative stress or free radicals and diseases and abnormalities suffered by segments of eye such as cornea, lens and retina. During a preferred administration of the invention, the active ingredient improving telomerase enzyme activity was administrated to the patient's eyes in drop form. The drop administration was repeated in daily dosages determined based on nature and severity of disease during the administration method mentioned herein. The drop administration process and dosages are determined individually for the patient and disease by taking into consideration variables such as course of patient's treatment or severity of disease. The greatest advantage of administration in drop form is that a patient can administer it on her/his own. It is observed that active ingredient administered in drop form prevents cataract formation, protects near vision and prevents presbyopia.

During another preferred administration of the invention, a compound containing the active ingredient activating telomerase enzyme was injected to the anterior chamber for treating an age related eye disease. It was observed that the active ingredient improving telomerase enzyme activity and mentioned herein stops reduction of number of cornea endothelium cells and thus protects cornea transparency.

During another preferred administration of the invention, the active ingredient improving telomerase enzyme activity was used in intravitreal form. It was observed that the active ingredient applied to the posterior chamber (intravitreal) protects the epithelium structure of retina pigment and age related macular degeneration (AMD) was not observed in these people.

The protection scope of this application is established on the claims section and it cannot be restricted to the incidents explained above, as examples, under any circumstances. It is clear that a person specialized in this technical field can present the innovation presented with the invention by using similar structures and / or adapt this structure in other fields used in the related technique with the same purpose. Thus, it is apparent that such structures will lack criteria of innovation and exceeding state of the art following our application.

Claims

1. The invention in a natural or synthetic (obtained in a laboratory) compound that helps preventing, delaying, stopping and / or healing age related eye conditions or diseases such as dry eye, arcus senilis, loss of near vision (presbyopia), iris atrophy, loss of pupil reactions, cataract, glaucoma, age related damages on nerve layer (AMD etc.) and optical nerve atrophy and it is characterized with containing an active ingredient that activates telomerase enzyme which is a reverse transcriptase having a ribonucleoprotein structure that catalyzes adding telomere repeats to telomeres of eukaryotic chromosomes.

2. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes in ophthalmic drop form.

3. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes in ophthalmic pomade form.

4. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes in ophthalmic gel form.

5. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes in sub-tenon injection form.

6. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes in subconjunctival injection form.

7. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes in subconjunctival extended release (short or long term) form.

8. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes as injection to the anterior chamber.

9. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes as injection to the posterior chamber (intravitreal).

10. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes as intravitreal extended release (short or long term).

11. It is the compound described on Claim and it is characterized with administering the active ingredient activating the telomerase enzyme mentioned herein by using it on eyes in peribulbar or retrobulbar injection form.

12. It is the compound described on Claim and it is characterized with externally administering the active ingredient helping to activate telomerase enzyme by using cornea or ophthalmic injection methods determined based on nature, course of diseases and condition of patient.

13. It is the compound described on Claim and it is characterized with the active ingredient improving telomerase enzyme activity in drop form, pomade form, gel form, sub-tenon injection, subconjunctival injection, subconjunctival extended release (short or long term), anterior chamber injection, posterior chamber (intravitreal) injection, intravitreal extended release (short or long term), peribulbar or retrobulbar injection form into the eye so that impacts of aging on tear film, conjunctiva, sclera, cornea, trabecular meshwork, iris, pupil, lens, blood vessels feeding the eye, choroid, ciliary body, retina and optic nerves can be delayed, stopped or improved.

14. The invention is a method of administering an active ingredient that enables treating age related or not age related eye diseases and abnormalities as well as delaying or stopping their effects; it is characterized with deciding whether it will be used in drop form, pomade form, gel form, sub-tenon injection, subconjunctival injection, subconjunctival extended release (short or long term), anterior chamber injection, posterior chamber (intravitreal) injection, intravitreal extended release (short or long term), peribulbar or retrobulbar injection based on the nature and course of disease and condition of the patient as well as planning a treatment optimum for the form of administering the active ingredient; administering the daily dosage to the patient according to the planned treatment or patient administering it to himself/herself and it is characterized with process steps such as telomerase enzyme activity in cells of ophthalmic structure is increased by the compound during the treatment; increased telomerase enzyme activity stops, delays or prevents cell aging or degeneration.