Modern Trends in Retinal Disease Treatment. Tissue-Specific Action Peptides

Retinal diseases (age-related macular degeneration, diabetic retinopathy, pigmentary retinitis) represent a complex problem for clinical ophthalmology. According to the WHO data for 2010, in the coming century, retinal pathology (along with cancer) will be the leading cause of disability in the world.

Currently, modern methods of treating retinal pathology include pharmacotherapy, laser treatment, and surgical treatment.

Pharmacotherapy is diverse but not very effective. In some countries, to reduce the risk of new eye complications, hemostatic agents, blood-improving drugs, glucocorticoid drugs, various biostimulants, and adaptogens are used. The main goal of conservative therapy is to influence the pathogenesis of retinal pathology. This explains the use of drugs that strengthen the vascular wall (angioprotectors), improve retinal trophism (adaptogens), block free radicals that occur due to disruption of oxidative-reductive processes (antioxidants), and so on. However, conservative therapy is effective only in the early stages of the process, and its results are unstable: it usually helps to stop or slow down further vision loss but does not improve it. Therefore, this method of treatment is used only as supportive therapy.

The use of anti-VEGF drugs (vascular endothelial growth factor) for the treatment of patients with wet forms of macular degeneration and diabetic retinopathy can be considered a therapeutic breakthrough. In recent years, innovative methods of conservative treatment of retinopathy accompanied by neovascularization have been actively developed and introduced. Ophthalmologists have gained access to new methods of blocking the vascular endothelial growth factor, which is considered a key element in the neovascularization process, as well as hyperfiltration of retinal vessels. Therefore, in recent years, this therapy has become the standard for treating this pathology.

It is known that VEGF belongs to homodimeric glycoproteins and structurally resembles platelet-derived growth factor. It has the ability to bind to five types of tyrosine kinase receptors.

VEGF affects the vascular wall at several levels: as a factor promoting the survival of endothelial cells, it increases vascular permeability and has properties of a potent vasodilator. Glomerulogenesis and the function of the renal glomerular filter are also strictly regulated by VEGF.

In addition to its physiological effect, VEGF also has other properties that are triggered by certain pathogenetic mechanisms and include the ability to stimulate the formation of collateral circulation necessary for the survival of hypoxic cells and to improve trophism in wound healing processes. However, many pathological processes, such as the development of diabetic retinopathy, tumor growth, the occurrence of ischemic diseases, etc., are caused by disruptions in the VEGF-VEGFR system.

The first studies showing that VEGF is a factor promoting vascular permeability in tumors were published in the early 1980s. Today, anti-VEGF drugs are used as part of complex treatment of metastatic lung tumors. VEGF inhibitors are recognized by monoclonal antibodies that can selectively bind to VEGF and block its action. As a result, neoangiogenesis in tumors is suppressed, which can contribute to further growth.

Recent research has shown that one of the methods of conservative treatment of diabetic retinopathy is a substance with anti-VEGF properties. In this clinical practice, there are several drugs that block the biological action of VEGF. These drugs include a medicinal selective inhibitor of VEGF165 and drugs that block any isoforms of VEGF.”

However, a new group of therapeutic drugs that ophthalmologists had hoped could help treat retinal pathology has turned out to be not entirely safe for clinical use. Among the ophthalmic manifestations of anti-VEGF drugs, endophthalmitis, lens damage, and retinal detachment are noteworthy as the most common complications. In addition to the side effects of intravitreal injection itself, other undesirable effects may occur.

Although anti-VEGF drugs are injected directly into the vitreous body through scleral puncture, the penetration of the drug into the systemic bloodstream is still possible. Consequently, this can lead to undesirable systemic manifestations, such as hypertension or proteinuria. Any increase in blood pressure will result from increased peripheral vascular resistance due to the suppression of nitric oxide production by endothelial cells, the formation of which is stimulated by VEGF through nitric oxide synthase activation. The same pathogenetic mechanism underlies kidney dysfunction and the development of proteinuria. Other complications identified as a result of anti-VEGF use include the suppression of tissue regeneration processes, leading to poor wound healing, cardiovascular system disturbances, and infertility. Cases of gastrointestinal bleeding have also been described. Therefore, potential systemic complications from the use of VEGF inhibitors (including hypertension, proteinuria, impaired wound surface regeneration, collateral circulation, etc.) can be life-threatening, especially in people with diabetes.

As a result, the use of these drugs has a number of contraindications (liver diseases, porphyria, decompensated arterial hypertension, unstable angina) and cannot be recommended for all patients, as it can lead to serious complications and further deterioration of their visual function.

Attempts at surgical treatment of yellow spot degeneration have not yielded the expected results. Several operations involving the transplantation of retinal pigment epithelium (RPE) from healthy retinal areas to damaged (macular) parts were performed. However, to date, this method of therapy is not used in clinical practice due to the technical complexity of such operations and the high risk of postoperative complications. Nevertheless, these data prove that the transplantation of healthy RPE cells subretinally into affected areas can be effective.

New possibilities for treating diseases of the posterior segment of the eye have emerged through laser therapy. Laser coagulation is used in the treatment of central and peripheral retinal dystrophy, certain types of tumors, as well as vascular and inflammatory diseases. Additionally, this method is used to prevent the progression of various forms of dystrophy and retinal detachment. Today, laser coagulation is considered one of the main methods of combating lattice dystrophy, diabetic retinal changes, retinal vein thrombosis, and the wet form of age-related macular degeneration. However, there have been clinical cases where laser coagulation can lead to the formation of fibrous tissue and worsen the course of the pathological process. Even the use of modern low-energy laser radiation, according to some authors, has several disadvantages.

Nevertheless, although there are numerous ways to treat macular degeneration of the retina and diabetic retinopathy, the treatment of degenerative retinal diseases such as pigmentary retinitis remains a significant challenge today. On one hand, this is due to the great diversity of its forms, and on the other hand, it is due to the lack of effective treatment methods.

In some countries, various vitamins, their derivatives, and mineral supplements are used to treat pigmentary retinitis. Vitamins A, E, and rutin are most commonly used in standard doses as antioxidants that reduce the excessive activity of peroxidases in retinal tissue. Indirect anticoagulants are prescribed to improve hemodynamics by reducing blood viscosity. However, anticoagulants should be used with great caution in elderly patients due to the risk of hemorrhagic complications. In the presence of concomitant diseases such as arterial hypertension, peptic ulcer disease, liver, and kidney diseases, anticoagulants should not be used.

In clinical practice, attempts have been made to stop the progression of the dystrophic process using revascularization surgeries, the main goal of which was to restore the trophism of the retina in the affected eye. The following operations were performed for this purpose: transplantation of fibers of straight, upper oblique, and lateral rectus muscles into the suprachoroidal space, scleroplasty with homograft from the sclera of corpses, retro-scleral plombage with placental suspension infusion, and symptomatic denervation. Sympathectomy was also performed. However, all these operations did not stop the progression of the pathological process and sometimes ended with severe complications in the form of circulatory disorders.

Thus, the action of these therapeutic measures (vasodilators, vitamins, tissue therapy, surgical interventions) is aimed solely at improving the trophism of the retina. The main drawback of these methods is the lack of pathogenetic direction. Therefore, the observed clinical improvement is unstable, and after some time, visual functions return to the original level, and the disease steadily progresses, leading the patient to blindness.

In recent decades, this issue has been studied, and new pathogenetic approaches to treatment are actively being researched. Researchers have largely focused on gene therapy. One promising method for treating pigmentary retinitis is based on the subretinal introduction of an adenovirus capsule containing mini-chromosomes.

Experience has been accumulated in the transplantation of retinal pigment epithelium cells and retinal neuronal cells. The surgical method of retinal cell transplantation is based on the use of a layer of pigment epithelial cells within the donor retina’s thickness. Transplantation contributes to the preservation of photoreceptors but does not affect the quality of vision.

Therefore, the development and study of drugs that determine the structural and functional specialization of retinal cells for the pathogenetic treatment of pigmentary retinitis remain relevant. Among physiologically active substances, peptides with tissue-specific action are of great interest, such as vascular peptides contained in the IPH AVN peptide complex, which, during the course of treatment, stimulate and strengthen the walls of blood vessels, making them elastic and robust.