Retina and Peptides — analytical review

The Head of the Analytical Group
Andrei ILNITSKI
Professor, DSc, PhD, MD

1. Retina as important part of communication of organism with the environment. Why we need new approaches to influence the retinal health

The retina and its health are the mirror of the body, and the general patterns of correct behavior improve both the health of the whole organism and the retina.

Retina is the inner shell of the eye, which is the peripheral part of the visual analyzer which before birth was the part of the brain; contains photoreceptor cells that provide perception and conversion of electromagnetic radiation of the visible part of the spectrum into nerve impulses, and also provides their primary processing. Frequently occurring retinal diseases that affect many people and need prevention and treatment with peptides — arterial hypertension and diabetes mellitus (the vessels feeding the retina are affected and destroyed, which reduces vision) and age-related macular degeneration of the retina (age-related malnutrition of the central retinal zone).

One of the main factors in increasing the prevalence of retinal diseases is age. Moreover, it is of great importance to be ahead of the biological age of the passport, which is being prevented by a new science called geroscience. Geroscience is a recently separated interdisciplinary field in which the laws of aging biology are studied, and biomedical gerontology is considered as a center for the prevention of diseases in which old age is the main etiological factor (for example, frailty syndrome). This approach is a fundamental possibility of slowing down the rate of dysfunctional aging, the possibility of delaying the development of chronic diseases associated with age, as well as the possibility of increasing the period of life without chronic diseases. Premature aging is characterized by a «negative» variant of biological age, which is an independent factor in the development of pathology at earlier stages of the life cycle, which is more characteristic of the elderly and senile age, in particular, neoplasms, Alzheimer’s disease, sensory (retinal) deficits, cardiovascular events and lung pathology, metabolic disorders, high adherence to infectious diseases. diseases, skin diseases. It is proved that biological age is a universal factor of prevention, and the biology of age and the biology of age–associated diseases have many points of contact. Synchronization of biological and chronological age will reduce the load of the «red zone» at the end of life.

There are more and more studies about changes in retinal peptides during aging. From previous studies, scientists knew that the levels of peptide called PEDF pigment epithelium factor in the retina fall as the body ages, but it was not clear whether the deficiency of this peptide is the cause or consequence of age-related changes. A new work by American scientists from the National Institute of Eye Diseases has shown that PEDF provides protective functions, and its loss leads to the disesases Scientists have shown for the first time that the simple removal of PEDF provokes many different gene changes that lead to aging of the retina. Thus, in mice without the PEDF gene, changes were observed in the nucleus of retinal pigment epithelial cells producing PEDF, which indicates violations in DNA packaging. In addition, activation of four genes associated with cellular aging and a decrease in the level of the PEDF receptor were noted. These and other detected changes are usually observed in the aging retina, the authors explain. The results indicate that the loss of PEDF is the driving force of age-related changes in the retina. Further studies will allow us to evaluate the effect of manipulations with PEDF for the treatment of age-related macular degeneration and other eye diseases leading to blindness.

Currently, life expectancy and aging are evaluated from the standpoint of so-called intrinsic capacity. This is a complex of all human abilities, thanks to which it is possible to describe his daily life. These abilities are grouped into several directions and if you are engaged in prevention, then you should influence all these positions or as they are called domains. Intrinsic capacity and the nature of aging from a clinical point of view is characterized in terms of the following domains:

1) cognitive (parameters of memory, self–control, ability to solve problems, orientation in space, ability to learn new skills, etc.),

2) motor (balance, gait, muscle mass and strength — in the modern sense of sarcopenia),

3) psychological (mood, attitudes to an active life, emotional background),

4) sensory (vision, hearing, smell, touch),

5) somatic (cardiorespiratory problems, neuroimmunoendocrine background, hormonal status, polypragmasia, etc.),

6) vital, whose condition is determined by the nature of nutrition.

The state of human health, which is reflected by these domains, depends on some basic peptides, which also have a great influence on the retina. Such peptides include the following.

The renin–angiotensin system (RAS) plays a major role in the regulation of blood pressure. Renin, a proteolytic enzyme derived from the precursor prorenin and primarily released by the kidneys, cleaves angiotensinogen to angiotensin I (AngI). AngI is further processed by angiotensin-converting enzyme (ACE) and ACE2 to different peptide cleavage products. Among them, angiotensin II (AngII) is the main effector of the RAS acting at the angiotensin type I and type 2 receptors (AT1R and AT2R). AngII also acts on the adrenal cortex, triggering the release of aldosterone, which binds to its receptor (mineralocorticoid receptor) and contributes to electrolyte and water balance in the body. Violation of the production and interaction of these peptides leads to an increase in blood pressure and hypertensive retinopathy. To prevent this disease, it is important not only to take antihypertensive medications, but also to lead a physically active lifestyle, have proper nutrition and take peptide supplements that improve blood supply to the retina.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the L-cells of the gastrointestinal tract in response to food. It stimulates glucose-dependent insulin secretion and inhibits the secretion of glucagon. GLP-1 and its receptor GLP-1R are expressed in the brain, where GLP-1 may affect multiple neural circuits and modulate feeding behavior and reward. Both GLP-1 and GLP-1R have been detected in human, rat, and mouse retinas at both the mRNA and the protein level. Although it has been localized mainly to the ganglion cell layer, GLP-1R has also been reported in a rat Müller cell line, suggesting that this receptor may be expressed by Müller cells in mammalian retinas.

Growth hormone (GH) have peptide nature and is produced in the pituitary and has many documented effects throughout the body, particularly on cell differentiation, proliferation, and survival. However, GH expression has also been found in tissues other than the pituitary. Indeed, the expression of genes or proteins related to GH has been reported in retinal ganglion cells of reptiles, birds, rodents, and primates, including humans, and low levels of GH in the human vitreous have been associated with retinal neurodegeneration. In the retina, GH is expressed together with the GH receptor (GHR), suggesting a local autocrine/paracrine mode of action. In addition, GH-releasing hormone (GHRH), which regulates the secretion of GH from the pituitary, is also expressed in the retina. In primate retinas, expression of GHRH, GH, and GHR has been reported in all nuclear layers and in the retinal pigment epithelium.

Neuropeptide Y (NPY) is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. NPY has been identified as the most abundant peptide present in the mammalian central nervous system. NPY is expressed and functionally active in different retinal cells of non-mammalian and mammalian species, where it can have paracrine or autocrine effects by acting on NPY receptors. The NPY receptors are expressed in different retinal cell types, such as photoreceptors, horizontal, amacrine and ganglion cells, Müller cells, and microglia.

Opioid peptides are known as powerful analgesics, but they are involved in a variety of functions in the organism. Their effects are mediated by δ, κ, and µ opioid receptor subtypes. Opioid receptors have been detected in virtually all major organ systems. In particular, the presence of functional opioid receptors has been reported in the retina, optic nerve, and optic nerve head astrocytes.

Somatostatin (somatotropin release inhibiting factor—SRIF) is considered to be one of the key physiologically active neuropeptides expressed in the retina. Five SRIF receptor subtypes coupled to different G-proteins have been cloned, namely sst1–5, and they modulate the actions of multiple second messengers/transduction pathways. SRIF receptors have been detected in different areas of the central nervous system, including the retina, where sst₁ and sst₂ are the most widely expressed in multiple retinal layers and cell types.

The peptides of the tachykinin family are characterized by a common C-terminal amino acid sequence (Phe–X–Gly–Leu–Met–NH2). Substance P (SP) is the best characterized neuropeptide of this family, but other tachykinins have also been described so far, the two main ones being neurokinin A (NKA) and neurokinin B (NKB). The tachykinins act thorough specific NK receptors, namely NK1R, NK2R and NK3R. SP, NKA, and NKB have the highest affinity for NK1R, NK2R, and NK3R, respectively, but they do not bind them in a selective manner.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) belong to a peptide superfamily that also includes secretin and glucagon. Their receptors are G protein-coupled receptors that can be classified into two groups: PAC1R, which binds PACAP with higher affinity than VIP, and VPAC receptors (VPAC1R and VPAC2R), which bind PACAP and VIP with similar affinities. VIP has been observed to support neuronal survival in both physiological and pathological conditions in the central as well as in the peripheral nervous system. Similarly, widespread neuroprotective properties of PACAP, mediated mainly by the PAC1R receptor, have been reported in a variety of in vitro and in vivo models and have been extensively reviewed [1].

Thus, maintaining general health, good functional ability contributes to the formation of the correct peptide profile of the body, which has a positive effect on the health of the retina.

2. General principles of maintaining eye and retinal health: importance of peptides.

In the previous section, we showed that the health of the retina is inseparable from the general condition of a person and his functional ability. However, with regard to the retina, there are some special rules for maintaining its health that must be followed.

— Let’s remind you again — follow a healthy lifestyle (healthy nutrition and physical activity, psychological support and the use of peptides and other supplements).

— Know your family’s health history. If there are cases of eye diseases in the family, then you should not forget about constant monitoring by a family doctor or an ophthalmologist.

— Wear glasses if prescribed.

— Use protective eyewear outdoors.

— Give your eyes breaks from the computer screen.

— Measure blood pressure and know the level of glycated hemoglobin, if you have high blood pressure and elevated glucose level in the blood, strive for their normalization.

And now let’s move on to more detailed recommendations for a healthy lifestyle to preserve the health of the retina from the point of view of peptides.

3. Retina as the mirror of health and healthy aging.

3.1 Peptides of retina and lifestyle (physical activity and peptide enriched nutrition).

The peculiarity of the peptide regulation of retinal health is that simple things — such as physical activity and nutrition — lead to the production of the necessary peptides that have protective properties. It is only important to choose the right level of physical activity and the right diet.

As a result of physical activity, special peptides called exerkins are produced in the retina and surrounding eye tissues. It is necessary to devote at least 150-300 minutes per week to moderate–intensity aerobic physical activity; or at least 75-150 minutes per week to high–intensity aerobic physical activity; or to devote time to a similar combination of moderate and high-intensity physical activity during the week. It is advisable to devote time to moderate or high intensity physical activity twice a week or more often, aimed at developing muscle strength of all major muscle groups, as this brings additional health benefits. Attention is drawn to the fact that it is advisable to limit the time spent in a sitting or lying position, since replacing being in a sitting or lying position with physically active activity of any intensity (including low intensity) benefits health.

The question often arises with what exactly, with what exercises should physical activity classes begin with in order to make them a routine to achieve better health. Here the recommendations are as follows:

• it is better to start «taking on yourself» with anaerobic loads – resistance exercises;
• then connect aerobic exercises in volumes no less than indicated in the previous slides;
• after steady training with resistance loads and aerobic physical exercises, stretching exercises can be added, and balance exercises (for example, tai chi gymnastics) are recommended for people of older age groups;
• it is important to observe the modern principle of healthy behavior – to organize time so that the slightest pauses are filled with physical activity («not a minute of rest»).

In general, regular physical activity has a positive effect on the state of somatic and other domains of intrinsic capacity, which include such as: reduction of mortality from all causes, including cardiovascular diseases; reduction of the incidence of hypertension, cancer of certain localizations (bladder cancer, breast cancer, colon cancer, endometrial cancer stomach and kidneys). Physical activity contributes to the prevention of falls syndrome and senile asthenia in older age groups, and also prevents or reduces the degree of obesity.

It is important to note that such a variety of positive effects of basic, minimally appropriate physical activity for health is mediated by signaling molecules of a peptide nature, which are called exerkins. Due to the fact that skeletal muscles make up about a third of body weight and play an important role in physical exercise, the effects of physical activity were initially attributed to myokines. For example, IL-6 myokine has been the most widely studied since its discovery in 2000. However, later, other humoral peptide factors were associated with physical activity, with sources of their production in the heart (cardiokines), liver (hepatokines), white adipose tissue (WAT; adipokines) and brown adipose tissue (BAT; batokines), nervous system (neurokins), retina (retinokines). Exerkin peptides include hormones with local autocrine effects (affecting the original cell) and paracrine effects (affecting neighboring cells).

Exerkins of a peptide nature have positive cardiometabolic effects, including helping to reduce the risk of cardiometabolic diseases and mortality, physical exercise mitigates traditional risk factors for cardiovascular diseases, such as obesity and dyslipidemia, have a direct effect on systemic inflammation and energy imbalance. Also, exerkins have a positive effect on the vessels of the retina, which improves its health. Exerkins enhance angiogenesis and reduce the severity of ischemic phenomena in different tissues, improve endothelial function. The interaction between the endothelium and certain established exerkins, such as nitric oxide 52 or VEGF27 peptide, affects vascular tone, inflammation, regeneration and thrombosis and plays an important role in cardiovascular and overall viability.

Exerkins, including the peptide plan, are also produced in the liver. Exercise has been proven to reduce liver steatosis regardless of weight loss. The liver is an important source of many circulating proteins and peptides, with ~2500 liver-secreted proteins and their fragments identified using modern liquid chromatography and mass spectroscopy technologies. It is currently known that peptides can be a source of influence on glucose and/or lipid metabolism (for example, angiopoietin-like protein 4 in humans and animal models), provide darkening of white adipose tissue (FGF21 peptide in the mouse model), activate lipolysis (FGF21 peptide in humans and in the mouse model) and maintain cellular homeostasis (heat shock protein 72 in humans). All these effects have positive properties for the retina, contributing to its revascularization.

Peptides that we get from food are important for health. The most valid and scientifically-based nutrition system is the Mediterranean diet, which contributes to the prevention of cardiovascular pathology, dementia and oncological neoplasms. The new trend of the Mediterranean diet is the preservation of vascular health, which includes the well-being of the retina. Now attempts are being made to isolate substances, including those of a peptide nature, which have a targeted preventive effect, that is, they prevent a particular pathology.

A striking example of the targeted effect of plant and animal peptides contained in the Mediterranean diet is the prevention of primary sarcopenia, which is characterized by a decrease in muscle strength and mass. These processes, as age increases, are partly related to an imbalance between protein synthesis and degradation in muscles, a process that can be facilitated by increasing the content of total protein, peptide and essential amino acids in food, stimulating an increase in the level of postprandial muscle protein. It is also important to understand that the quantity, quality and variety of physical exercises as a supplement to a proper diet is the key to a healthy lifestyle: focused on muscles throughout the human life cycle. Studies conducted to date show that the analysis of various peptide components of plant foods and their complex interactions with the human body is important for modulating the nutrition profile.

From the point of view of the formation of muscle health, peptide or peptide-containing diets have significant effects, which stimulate the production of their own proteins by muscles and inhibit their degradation, causing a positive relationship between the use of proteins and essential amino acids with muscle strength and volume. Satisfaction of these needs increases with aging, since in older age groups we observe the addition of such conditions as age-related anorexia, swallowing disorders and economic problems (they cannot buy good-quality food for retirement). In this regard, after 65 years, to maintain normal muscle metabolism, it is necessary to use protein and peptides in the amount of 1 – 1.2 g / kg of body weight (PROT-AGE and ESPEN studies), with severe kidney pathology without dialysis therapy – 0.8 g / kg of body weight. Also, using diets enriched with peptides, it is necessary to understand that due to unsatisfactory dental health, there is a shortage of meat consumption, because the biological meaning of nutritional support by proteins in such a situation is their metabolism to short–chain fatty acids (propionate, butyrate, acetate), which stimulate muscle anabolism and have an anti-inflammatory effect. The biological meaning of nutritional support with peptides and essential amino acids (leucine is the most important in this situation) is the activation of rapamycin (mTOR) and inhibition of proteosomal oxidation, and the dosage of leucine should be 3 grams, other peptides and amino acids – up to 10-15 grams / day. Let’s add that such an important amino acid for muscle health as leucine enters the body independently or as part of peptides of natural origin, the main sources of leucine are hazelnuts, beans, soy flour, brown rice, egg white, meat (beef fillet, salmon, chicken breasts), whole wheat. These components of the medium have multiple positive effects on the human body, such as lowering glucose levels, providing nitrogen balance necessary for the process of protein and carbohydrate metabolism, preventing the development of asthenia associated with hyperproduction of serotonin, immunomodulation, participation in wound healing, anabolic effects on muscles. Maintaining muscle health is important for the health of the eye and retina, since the organ of vision is surrounded by muscle tissue and its activity depends on it to a high degree.

The team studied fruit flies and cutting-edge brain cell models called organoids. They focused on the signals muscles send when stressed. The researchers found that stress signals rely on an enzyme called Amyrel amylase and its product, the disaccharide maltose. The scientists showed that mimicking the stress signals can protect the brain and retina. The signals work by preventing the buildup of misfolded protein aggregates. Findings suggest that tailoring this signaling may potentially help combat neurodegenerative conditions like age-related dementia and Alzheimer’s disease. “We found that a stress response induced in muscle could impact not only the muscle but also promote protein quality control in distant tissues like the brain and retina,” said Fabio Demontis, PhD, of St. Jude Developmental Neurobiology. “This stress response was actually protecting those tissues during aging.” [2].

To ensure the full intake of peptides of plant and animal origin into the body, it is advisable to observe the following principles of the resistance diet developed by us, that is, a nutrition system that increases human viability:

1) moderate nutrition, but quite sufficient – at least 2500 calories per day.

2) the composition of the diet may be of the following character — any cereals that are valuable sources of plant peptides and fiber, necessarily rice, wheat, corn, buckwheat, oatmeal, which should give us about 800 kilocalories per day (this is about 200-250 grams), the diet under discussion is focused largely on plant products. All tuberous crops, including potatoes, are recognized as harmful, as they relate to easily digestible carbohydrates that lead to obesity, diabetes mellitus, and the development of inflammation in general. The maximum portion of potatoes is allowed no more than 50 grams per day, or 39 calories.

3) daily consumption of 500 grams of fresh vegetables and fruits is recommended, which should be divided into 5-6 receptions, moreover, 300 grams should be vegetables, and 200 — fruits. It is important to include whole milk or cheese in the diet for middle-aged people. For the elderly, it is better to use fermented milk products. They need to be consumed 250 grams per day or 153 calories per day. Vegetable products contain many peptides that are useful for the retina.

— Grain-derived peptides. Grain protein is well studied as a source of hypotensive peptides, and most of the studies have confirmed its effect in in vivo studies. Rice (Oryza sativa), one of the three major grains consumed worldwide, serves as a staple food for almost half of the global population. Rice protein has been well studied as a source of anti-hypertensive peptides. Leu-Arg-Ala was isolated from thermolysin-digested rice bran; its hypotensive effect was demonstrated in human clinical studies. Normalization of blood pressure contributes to maintaining the health of the retina by improving its blood supply.

— Soybean protein-derived peptides. Soy protein has been well studied as a source of hypotensive peptides. The peptides, Gly-Tyr and Ser-Tyr, were isolated from pepsin-digested soy protein. Soy sauce containing soy protein digests, including Gly-Tyr and Ser-Tyr, exhibited anti-hypertensive effects in a clinical study involving prehypertensive and grade 1 hypertensive people. While the hypotensive effect was not observed in human clinical studies, few peptides derived from soy protein showed hypotensive effects in experimental studies.

— Vegetable-derived peptides. Rapeseed is an oilseed plant that is cultivated worldwide. Rapeseed meal is a byproduct of the oil removal process and is composed of approximately 40 % protein. Four hypotensive peptides were isolated from enzymatically digested rapeseed protein; three peptides were ACE-inhibitory peptides, and the other possessed the unique mechanisms of the rapakinin peptide.

— Seaweed and alga-derived peptides. Seaweed protein has also been well studied, and peptides derived from certain seaweed algae are commercially used. The anti-hypertensive and retinoprotective effect of protease digested wakame (Undria pinnatifida) has been demonstrated in a human clinical study and is now used for FOSHU in Japan. Val-Tyr, Ile-Tyr, Phe-Tyr, and Ile-Trp were isolated as functional ACE-inhibitory peptides, and their hypotensive effects were reported [3].

4) beef, pork, and in general, any red meat is undesirable when systematically consumed in large quantities, a maximum of 7 grams per day or 31 calories. The fact is that it has now been proven that red meat contributes to the development of malignant neoplasms, for example, prostate cancer in men. Protein should come from a number of other sources, as it is vital, so poultry is welcome — chicken or turkey, 29 grams per day or 62 calories. Plus fish — 28 grams per day or 40 calories.

3.2 Peptides and aging: macular degeneration (peptides as new horizon of senotherapeutic strategies).

Age-related macular degeneration (AMD), a degenerative disease in the central macula area of the neuroretina and the supporting retinal pigment epithelium, is the most common cause of vision loss in the elderly. Although advances have been made, treatment to prevent the progressive degeneration is lacking. Age-associated senescent cells exhibit abnormal metabolism, increased generation of reactive oxygen species, and a heightened senescence-associated secretory phenotype that nurture a proinflammatory milieu detrimental to neighboring cells. Senescent changes in various retinal and choroidal tissue cells including the retinal pigment epithelium, microglia, neurons, and endothelial cells, contemporaneous with systemic immune aging in both innate and adaptive cells, have emerged as important contributors to the onset and development of AMD. The repertoire of senotherapeutic strategies such as senolytics, senomorphics, cell cycle regulation, and restoring cell homeostasis (peptides) targeted both at tissue and systemic levels is expanding with the potential to treat a spectrum of age-related diseases, including AMD [4].

3.3 Peptides and diseases of retina: new in the treatmemt of diabetes

Investigators at the Joslin Diabetes Center and Beetham Eye Institute have identified certain endogenous protective factors that help prevent complications such as advanced retinopathy from developing in some people with type 1 diabetes. Profiling compounds extracted from retinal and vitreous tissues from human cadavers, the researchers found elevated levels of four proteins in individuals who had not developed sight complications. One peptide, retinal binding protein 3, was shown to protect both the neuroretina and the vascular retina from diabetes-induced retinal disease, in part by helping to inhibit retinol-cell uptake of glucose, thus dampening the production of inflammatory factors linked to retinal disease [5].

4. Schemes of peptides using in combination with lifestyle and behavior interventions for various diseases and conditions leading to retinal pathology.

The use of peptides in combination with other methods in improving health in domains of intrinsic capacity, In general, peptides can be classified by origin into natural (animal, vegetable) and synthetic (short, biomimetic); by the way of introduction to organism — oral administration, by injection; by the way of registration as medicines, biologically active food additives, as part of diets, sports and functional nutrition.

In terms of the mechanism of action, it was experimentally established that short peptides regulate the activity of genes by coplementary binding to a specific DNA site, that is, they have a gene-specific tropicity and are directly involved in the mechanisms of epigenomic regulation. Peptides in such an embedded position transmit information to a strictly defined type of cell synthesis of tissue-specific proteins. This means that a particular peptide with a certain sequence of amino acids acts on a strictly defined type of biological processes in the cell. Pathogenetically, the mechanism of peptide regulation can be reduced to the following sequential stages: complementary interaction of short peptides with DNA; changes in gene expression (activity) and activation of the production of strictly defined proteins; regulation of biochemical and physiological processes (antiaging effect). That is, the peculiarity of short peptides is that they do not act on the principle of «substitution» therapy, but modulate the activity of the cell’s genetic apparatus and regulatory processes in such a way that they transfer the cell to the most rational mode of functioning.

It should be noted that the use of peptides is a fundamentally new approach in treatment and prevention. Their peculiarity is that the drug, by affecting the cell genome, promotes gene expression and enhances the production of certain proteins with a beneficial sanogenic or therapeutic effect. In this case, the amount and degree of synthesized protein is determined by the potential of the cell and is regulated by subtle intracellular mechanisms. This determines the physiology of the effect of short peptides, which is especially important in the practice of, for example, aesthetic medicine.

The side effects of any peptides include allergic reactions and individual intolerance, with the oral use of peptide drugs in high doses, cases of the development of irritable bowel syndrome have been described. In general, peptide preparations are characterized by good tolerability, however, when using them, it is worth clarifying the allergological history and, if there are allergic reactions in the past, be careful in their use, ensuring the staging of allergic tests and subsequent dynamic observation.

As for the specific retinal-oriented effects, the retinoprotective effects of peptides have been investigated and here we provide a summary of the findings of the last few years.

Recent evidence indicates that physiological expression levels of peptides in the retina are necessary to maintain retinal integrity. Indeed, retinas of mice were characterized by abnormal sprouting of horizontal and rod bipolar cell dendrites, decreased ganglion cell number, altered MAPK signaling pathway, and GFAP upregulation in Müller cells, which is known to appear in response to retinal injury. In addition, peptides of retinas displayed significantly worse structural and functional damage with respect to wild types following lipopolysaccharide-induced eye inflammation, confirming that peptides expression in the retina may represent a natural defense against injury. So, in such cases the additional supplementation with peptides are necessary.

Intravitreal administrations of peptides have been shown to inhibit apoptosis and promote survival of retinal ganglion cells in different models of retinal injury. Since peptides is subjected to rapid enzymatic hydrolysis in the extracellular environment, the efficacy of a more stable, cyclized form of retinal peptides has been tested both in vitro and in vivo. In these studies, RGC-5 cells exposed to ultraviolet irradiation showed decreased apoptosis and less ROS generation when treated with cyclic peptides.

Peptides has been found to be very effective in protecting the retina from ischemia. In an ex vivo model, peptides decreased apoptosis and glutamate accumulation, reduced peroxidized lipids and inflammatory mediators, and induced normalization of glutathione homeostasis. In addition, peptides decreased VEGF expression, which was observed to increase in the ischemic retina. In the BCCAO model, intravitreal peptides was observed to ameliorate ERG responses, while intravitreal administrations of maxadilan (a peptide agonist) dose-dependently reduced the thinning of retinal layers and the loss of cells in the ganglion cell layer. The ischemic damage was also combated by topical administrations of different formulations of peptides through eye drops. Similar to intravitreal delivery, peptide eye drops protected the retina from thinning and from cell loss, while they also reduced upregulation in Müller cells.

Some studies have investigated possible effects of peptides against retinal damage caused by diabetic retinopathy. Both peptide administration to ex vivo retinal explants treated with diabetic stressors and peptide intraocular delivery in rats with STZ-induced diabetes protected the retina from apoptosis, maintained retinal synaptic integrity, and prevented the expression of inflammatory cytokines. Interestingly, retinal peptides protective and antiapoptotic effects were paralleled by inhibition of upregulation of HIF1-α, of VEGF, and of VEGF receptors (VEGFRs) in retinal explants and in pigment epithelial cells of the ARPE-19 cell line [1].

Thus, peptides are a group of drugs used in medicine and healthcare, which are based on a short sequence of amino acids that affect the activation of the production of endogenous anti-aging signaling molecules and the relative concentration of anti-aging molecules decreases.

In conclusion, we note that the retina of the eye is able to produce its own peptides under the influence of a proper lifestyle. However, to potentiate the positive effects of endogenous peptides, it is advisable to use supplements from peptides. Surely, the right way of life is the thing that is in the hands of the person himself. However, we warn you against self-medication. Regular medical examinations and timely diagnosis and prescribed treatment are the most important factors of health. Neverseless the modern use of peptides is based on the principle of individuality and holistic approach and is focused on supporting health and functionality in the domains of intrinsic capacity. Peptides have some side effects in the form of individual intolerance and allergic reactions, but are generally well tolerated and can be recommended to a wide range of people.