[The role of endothelin-1 in the pathogenesis of familial exudative vitreoretinopathy]. / Rol' endotelina-1 v patogeneze semeinoi ekssudativnoi vitreoretinopatii.

Familial exudative vitreoretinopathy (FEVR) is a rare hereditary disease characterized by pathological retinal vascularization with a progressive and variable course. The mechanisms of disease progression remain unclear. One substance that plays an important role in the pathogenesis of retinal vascular diseases is endothelin (ET). It was found that tissue hypoxia enhances the expression of the gene encoding ET-1, and ET-1 can be locally produced in the eye. PURPOSE: The study evaluates the possible role of endothelin-1 in the pathogenesis of FEVR. MATERIAL AND METHODS: The study included 85 patients with FEVR aged from 1 months to 17 years who were examined in Helmholtz National Medical Research Center of Eye Diseases. The concentration of ET-1 was evaluated in 19 patients with FEVR in the blood serum (n=17), lacrimal fluid (n=18) and 16 patients from the control group. RESULTS: The median of ET-1 in the lacrimal fluid in patients with FEVR was 13.74 pg/mL, respectively, which exceeded the same indicator of the control group 4.66 pg/mL by 2.5 times (p<0.001). The median of ET-1 in the blood serum exceeded the control group by 2.4 times (21.61 pg/mL and 9.21 pg/mL, respectively, p<0.001). CONCLUSIONS: An increase in the concentration of ET-1 in the lacrimal fluid and blood serum of patients with FEVR in comparison with the control group indicates its involvement in the pathogenesis of the disease.

Enalaprilat as a new means of preventing the development of retinopathy of prematurity.

In a rat model of experimental retinopathy of prematurity (ROP), the safety of enalaprilat and its effect on the level of angiotensin-converting enzyme (ACE) and angiotensin-II (AT-II) in the vitreous body and retina were investigated. The study was performed on 136 newborn Wistar rat pups divided into 2 groups: group A - experimental (animals with ROP, n=64) and group B - control (n=72). Each group was further divided into 2 subgroups: A0 and B0 (n=32 and n=36, respectively) - animals that did not receive injections of enalaprilat, and A1 and B1 (n=32 and n=36, respectively) - animals treated with daily intraperitoneal (i.p.) injections of enalaprilat (0.6 mg/kg of body weight). This treatment started on day 2 and lasted either to day 7 or to day 14 in accordance with the therapeutic scheme. Animals were taken out of the experiment on day 7 and day 14. In samples of the vitreous body and retina, the content of ACE and AT-II was determined by enzyme immunoassay. On day 7 in subgroups A1 and B1 the levels of ACE and AT-II in the vitreous did not differ, while on day 14 were lower than in subgroups A0 and B0, respectively. Changes in the parameters studied in the retina were somewhat different from those found in the vitreous body. On the seventh day, the level of ACE in the retina of animals of subgroup B1 did not differ significantly from subgroup B0, and in subgroup A1 it was increased compared to subgroup A0. On day 14, its significant decrease was noted in subgroups A1 and B1 as compared with subgroups A0 and B0. At the same time, the level of AT-II in the retina of rat pups of subgroup B1 was lower than in subgroup B0, both on day 7 and day 14. On day 7, the concentration of AT-II, as well as the concentration of ACE, increased in subgroup A1 as compared to subgroup A0. On day 14, this parameter in subgroup A1 was significantly lower as compared to subgroup A0, but significantly higher than in subgroup B1. It should be noted that i.p. injections of enalaprilat, increased a death rate of animals of both groups. The use of enalaprilat, starting from the preclinical period of the ROP development, led to a decrease in the activity of the renin-angiotensin system (RAS) in ROP animals at the onset of retinopathy in the experimental model used. This opens up prospects for considering enalaprilat as a means of preventing the development of this pathology; however, the recognized high toxicity of the drug requires further studies and correction of the timing of its administration and dosage in order to achieve a balance of efficacy and safety of use in order to prevent the development of ROP in children.

[Pathogenetic role of multifunctional protein alpha-2-macroglobulin and its activity in tears and serum in age-related macular degeneration and proliferative diabetic retinopathy]. / Patogeneticheskaya rol' polifunktsional'nogo belka α2-makroglobulina i ego aktivnost' v sleze i krovi pri vozrastnoi makulyarnoi degeneratsii i proliferativnoi diabeticheskoi retinopatii.

Alpha-2-macroglobulin (α2-MG) is a multifunctional protein involved in neurodegeneration, inflammation and neovascularization, which are key processes in the pathogenesis of age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR). AMD and PDR are two of the main causes of vision loss and blindness, are difficult to treat, and are generally diagnosed at the stage of irreversible changes. PURPOSE: This study estimates the activity of α2-MG in the blood serum and tears of patients with AMD and PDR in order to reveal the relation of its levels with the intensity of the pathological process in the retina. MATERIAL AND METHODS: The study included 17 patients (34 eyes) with AMD, 15 patients (30 eyes) with PDR, and 15 healthy adults (30 eyes) of the similar age. The activity of α2-MG in serum and tears was measured enzymatically using the specific substrate N-benzoyl-DL-arginine-p-nitroanilide (BAPNA). RESULTS: The activity of α2-MG in tears of patients with AMD was on the average 3.5 times higher than in healthy controls, and in patients with PDR - 1.5 times higher. Patients with AMD at the submacular fibrosis stage showed decreased α2-MG activity in tears. The activity of α2-MG in serum of patients with AMD and PDR was on the average 25% higher than in healthy persons. No correlation was revealed between serum and tear levels of α2-MG activity. CONCLUSION: This study revealed for the first time that in AMD and PDR the activity of α2-MG in tears is increased, and that in AMD the increase is higher than in PDR. An increase of α2-MG activity in serum confirms the presence of systemic inflammation. Absence of correlation between the serum and tear activity of α2-MG confirms its local origin. The high level of α2-MG activity in tears reflects the presence of an active destructive process in the retina, justifying its further investigation as a predictor of AMD and PDR course, as well as an indicator of therapy effectiveness.

[Changes of a2-macroglobulin activity and endothelin-1 concentration in tears of rabbits after transplantation of retinal pigment epithelium cells derived from the induced pluripotent stem cells]. / Izmenenie urovnia a2-makroglobulina i éndotelina-1 v sleznoi zhidkosti krolikov posle transplantatsii kletok retinal'nogo pigmentnogo épiteliia, differentsirovannykh iz indutsirovannykh pliuripotentnykh stvolovykh kletok.

Retinal diseases accompanied with the dysfunction or death of the retinal pigment epithelial (RPE) cells are widespread, hard to treat, and appear to be a leading case of visual loss and blindness among the persons older than 55 years. Transplantation of RPE cells derived from the induced pluripotent stem cells (IPSC-RPE) is a promising method of therapy for these diseases. To ensure the transplant survival instant follow-up is required. It can be based on biochemical analyses of tear fluid that can be easily non-invasively collected. For the post-transplantation process monitoring we have choosen such polyfunctional bioregulators as α2-macroglobulin (α2-MG) and endothelin-1 (ET-1). RPE atrophy in New Zealand Albino rabbits was modeled via the subretinal injection of bevacizumab. IPSC-RPE in suspension or as a monolayer on the scaffold were transplanted subretinally 1 month after the injection. α2-MG activity and ET-1 concentration in tears were estimated during the first month and after 2, 3 and 7 months after transplantation. On the 7-14 days after transplantation α2-MG activity increased in tears of the both operated and controlateral eye probably as a reaction on the corticosteroid therapy. In 50% rabbits there was one more increase after 2-3 months that could be due to the immune inflammation. Concentration of ET-1 in tears decreased dramatically on the 7-14 days and 7 months after transplantation, and it could have an influence upon the retinal vassal tone. The data obtained show that estimation of bioregulators in tears can help monitoring local metabolic processes after RPE transplantation that is necessary for the opportune, reasonable and focused medicamental correction of post-transplantation process.

[Bradykinin and angiotensin-converting enzyme in serum of patients with diabetic retinopathy and the prognosis of diabetic macular edema development (pilot study)].

BACKGROUND: Diabetic macular edema (DME) is a microvascular complication of diabetic retinopathy. One of the key roles in the pathogenesis of DME may belong to the components of rennin-angiotensin and kallikrein-kinin systems: bradykinin (Bk) and angiotensin-converting enzyme (ACE). PURPOSE: To determine the Bk and ACE concentration and ACE activity in serum of patients with proliferative diabetic retinopathy (PDR) and to estimate the significance of these parameters for the early diagnostic and prognosis of DMO. MATERIALS AND METHODS: Serum was collected from the 2 groups of patients with II type diabetes. Group I (n=9) had DME, group II (n=27) had PDR without DME. Control group (n=14) consisted of adult volonteers without diabetes and ophthalmic diseases. Concentration of Bk and ACE was measured using ELISA kits, ACE activity was determined enzymatically with specific fluorogenic substrate. RESULTS: Concentration of Bk in serum of patients without DME did not differ from one in controls (12,00 (9,70; 12,40) pg/ml) while all patients with DME had Bk level of 14,69 (13,68; 16,78) pg/ml that was significantly higher (p<0,01). In patients without DME ACE concentration (88,60 (77,30; 97,45) ng/ml) and ACE activity (6,8 (5,1;7,1) nmol/min·ml) were higher than normal (p<0,01) while in the case of DME concentration of ACE increased (77,36 (70,24; 86,29 ng/ml, p<0,01) and activity remained normal. The Bk/ACE concentrations ratio decreased in patients without DME and increased in those having DME. CONCLUSION: Patients with DME have increased Bk concentration along with nearly normal ACE concentration that indicate predominance of Bk synthesis over its degradation that may lead to the DME development. The Bk/ACE ratio decrease in patients with uncomplicated PDR and increase significantly in ones with DME. It means that determination of Bk in serum of patients with PDR may be used for the prediction of DME development. The Bk/ACE concentrations ratio may be even more informative.

[Pathogenetically oriented approach to prevention of retinopathy of prematurity (experimental study)]. / Patogeneticheski orientirovannaya profilaktika retinopatii nedonoshennykh (eksperimental'noe issledovanie).

Intraperitoneal injections of exogenous melatonin during the development of the retinal vascular system in experimental rats has been shown in a number of experimental studies on the model of EROP to prevent the appearance of histological signs of the development of experimental retinopathy of prematurity (EROP), stabilize the blood-retinal barrier and have a pronounced antioxidant effect, but pathogenetic basis for these phenomena hasn't been studied. PURPOSE: To study the influence mechanism of melatonin and its analogues on the development of EROP at the preclinical stage of the pathological process to substantiate new approaches to prevention of ROP. MATERIAL AND METHODS: The study included 42 Wistar rat pups (84 eyes) divided into 6 groups: control group, experimental group (rat pups with EROP), experimental groups who underwent injections of melatonin and its analogues K-148, AL-3, K-096. The pups were euthanized on day 7 (4-5 pups from each group at each study period), binocular enucleation was performed, and the content of hypoxia-induced factor1α (HIF-1α) and VEGF-A was determined in retinal samples. RESULTS: The intraperitoneal injections of melatonin and its analogs led to a significant decrease in the level of HIF-1α and VEGF-A in the retina of the rat pups of the experimental group until the beginning of pathological vasoproliferation. CONCLUSION: Melatonin and its analogues are able to prevent the development of EROP by reducing the level of angiogenic factors in the retina of rat pups at the stage of existing avascular zones, which allows for them to be considered as a new promising approach to preventing the development of ROP.

Molecular Mechanisms and Clinical Manifestations of Catecholamine Dysfunction in the Eye in Parkinson's Disease As a Basis for Developing Early Diagnosis.

This review provides information on the non-motor peripheral manifestations of Parkinson's disease (PD) associated with a pathology of the visual analyzer and the auxiliary apparatus of the eye. The relationship between neurodegenerative processes that take place in the brain and in the eye opens new prospects to use preventive ophthalmologic examination to diagnose PD long before the characteristic motor symptoms appear. This will encourage the use of neuroprotective therapy, which stops, or at least slows down, neuronal death, instead of the current replacement therapy with dopamine agonists. An important result of an eye examination of patients with PD may be a non-invasive identification of new peripheral biomarkers manifesting themselves as changes in the composition of the lacrimal fluid.

[The role of the endothelin system in the pathogenesis of eye diseases]. / Rol' éndotelinovoi sistemy v patogeneze glaznykh boleznei.

The endothelin system (ES) plays a complex role in the pathogenesis of various eye diseases as a local regulator of vascular tone as well as many other physiological processes. Components of ES - endothelins and their receptors - can be found nearly in all cellular structures of the eye, their concentration increases in the presence of many eye diseases. In glaucoma, ES is involved in the mechanisms of eye hypertension by influencing the secretion and outflow of aqueous humor. The increase of endothelin level leads to the decrease of perfusion pressure, hypoxia, astrocyte proliferation, increase of density and rigidity of lamina cribrosa, apoptosis of neural cells, and has a profibrogenic effect. In retinal pathology, increase of endothelins disturbs autoregulation of retinal blood vessels changing the neurovascular interactions, breaks intercellular contacts in the retina, promotes neoangiogenesis. In diabetic retinopathy, ES contributes to the development of microangiopathy and proliferative vitreoretinopathy. The review discusses the possibility of correcting ES activity in the eye with medications by influencing its synthesis, cleavage and receptor binding.

[The effect of intravitreally administered angiogenesis inhibitor on the concentration of angiotensin-converting enzyme in the blood serum and lacrimal fluid in patients with diabetic macular edema].

BACKGROUND: Diabetic retinopathy (DR) is one of the more serious complications of diabetes and the main cause of blindness among working-age individuals. In recent years, information has emerged on the possible role of the renin-angiotensin system (RAS) in the pathogenesis of DR, and DR's possible connection with the system of pro-angiogenic factors. AIM: To study the impact of anti-angiogenic therapy on systemic and local concentrations of angiotensin-converting enzyme (ACE), a key component of RAS, for patients with diabetic macular edema (DME). MATERIAL AND METHODS: The concentration of ACE in the lacrimal fluid and blood serum in 10 patients (20 eyes) with DME was determined before and after intravitreal injection (IVI) of ranibizumab. The comparison group consisted of 7 patients (14 eyes) with age-related macular degeneration (AMD). The control group consisted of 10 healthy individuals (20 eyes). All groups were comparable in age and sex. The concentration of ACE was determined by enzyme immunoassay. The main group was examined four times: before IVI of ranibizumab, and then one week, two weeks and one month after IVI of ranibizumab. The comparison group was examined before, and then one week after, IVI of ranibizumab. RESULTS: In patients with DME, there was an initial 1.8-fold increase in the concentration of ACE in the lacrimal fluid of both eyes. A week after IVI of ranibizumab, the concentration of ACE in the lacrimal fluid began to decrease, reaching the control level after two weeks, and remaining there one month after IVI of ranibizumab. Initially, the concentration of ACE in the blood serum in patients with DME was 2.2 times lower than the control level. After IVI of ranibizumab there was an increase in the concentration of ACE in the blood serum, but by the end of the observation, the indicators continued to remain well below the control level. In patients with AMD, the initial concentration of ACE in the lacrimal fluids was not elevated; the concentration of ACE in the lacrimal fluids decreased 1.4 times one week after IVI of ranibizumab. The concentration of ACE in the blood serum of the patients with AMD was initially 25% lower than the control level, and essentially did not change after IVI of ranibizumab. СONCLUSIONS: Changes in the concentration of ACE in patients with DME may be a new prognostic criterion for the development of DME for patients with diabetes. These changes in the concentration of ACE, in the context of antiangiogenic therapy, indicate an interaction between the renin-angiotensin and angiogenic systems. Similar changes that were observed after IVI of ranibizumab in patients with AMD confirm the mutual influence of these two systems. The data presented in this study open up prospects for finding new pathways of pathogenic therapy for diabetic macular edema and diabetes.

Tear Fluid Catecholamines As Biomarkers of the Parkinson's Disease: A Clinical and Experimental Study.

An important approach to an early diagnosis of Parkinson's disease (PD) is screening for peripheral biomarkers in patients at the early clinical stage. In this study, we evaluated catecholamine concentration changes in the tear fluid of untreated PD patients as biomarkers. Norepinephrine and dopamine concentrations in the tear fluid of patients were found to increase compared to those in age controls, which was especially pronounced on the side where motor symptoms appeared. On the contrary, the epinephrine concentration in the tear fluid of patients was reduced bilaterally. Since there was no reason to consider the markers found in the clinical stage of PD as markers of the preclinical stage, we additionally studied the tear fluid composition in mouse neurotoxic models of PD preclinical and clinical stages. The norepinephrine concentration in the tear fluid of mice from the clinical stage model was found to be higher than that in controls; in the preclinical stage model, the norepinephrine concentration had a tendency to increase. Therefore, both PD patients and mice from PD preclinical and clinical stage models manifest unidirectional changes in their tear fluid compositions, which may be considered as promising biomarkers for the development of early diagnosis.

Biochemical and Functional Changes in the Eye As a Manifestation of Systemic Degeneration of the Nervous System in Parkinsonism.

Parkinson's disease (PD) is a systemic neurodegenerative condition caused by the death of dopaminergic neurons of the nigrostriatal system of the brain. This disease is diagnosed after most neurons have already been lost, which explains the low efficiency of treatment. Hope for increasing treatment efficiency rests in the development of new strategies for early diagnosis of PD based on a search for peripheral markers that appear as early changes in non-motor functions. Since impairment of the visual function is one of the manifestations of PD, the purpose of our work was to identify biochemical and physiological changes in a mouse's eye and eyelid in models of preclinical (presymptomatic) and clinical (symptomatic) stages of PD. We found that the norepinephrine, dopamine, and serotonin levels in the mouse eye reduced not only in the model of the early clinical stage, but also in the model of preclinical stage, an indication that pathological changes in the monoaminergic systems of the brain had affected the eye even before the motor disorders emerged. Moreover, in both models of PD, mice had increased intraocular pressure, indicating the development of both metabolic and functional impairments, which can be used as diagnostic markers. Unlike in the eye, the serotonin level in the eyelid was increased in mice at both parkinsonism stages and in presymptomatic mice to a much higher extent than in symptomatic ones. Given that serotonin is involved in the regulation of lacrimal glands of the eyelid, an increase in its level in parkinsonian mice should alter the composition of tear fluid, which could serve as a diagnostic marker of early stage of PD. Thus, the changes in the metabolism of monoamines in the eye and eyelid observed in mice at the early stage of parkinsonism are accompanied by changes in the function of these structures and, therefore, can be used as diagnostic markers of the early stage of PD.

[Endothelins and dopamine levels in tears for assessment of neurovascular disorders in glaucoma]. / Éndoteliny i dofamin v sleznoi zhidkosti v otsenke neirovaskuliarnykh narushenii pri glaukome.

PURPOSE: To estimate the possibility of detection of neurovascular ocular disorders in glaucoma by assessing the content of catecholamines and endothelins in lacrimal fluid. MATERIAL AND METHODS: The study included 47 patients with primary open-angle glaucoma (POAG). Tear eluate was analyzed by high performance liquid chromatography (HPLC) for catecholamines concentrations, and enzyme-linked immunoassay (ELISA) was used for evaluation of endothelins content. RESULTS: Endothelin-1 (ET-1) and big endothelin (bET) content in tears of patients with POAG was higher than in healthy controls. Concentration of dopamine (DA) in tears was lower and concentrations of L-dioxyphenylalanine and dihydroxyphenylacetic acid had a tendency for decrease. Noradrenaline content was equal in patients with POAG and controls. Adrenaline was not detected in any tear samples. CONCLUSION: Multidirectional changes of endothelins and DA levels in tears of patients with POAG was found. The increased concentration of ET-1 and its precursor bET promote vasoconstriction and decrease of aqueous humor outflow. The decrease of DA concentration is typical for neurodegenerative processes. Estimation of DA and endothelins concentrations in tears can enable early detection of neurovascular disorders in glaucoma patients and help evaluate their severity.

[Ophthalmic disorders as a manifestation of Parkinson's disease]. / Patologiia organa zreniia kak odno iz proiavlenii bolezni Parkinsona.

Parkinson's disease is a severe neurodegenerative disease accompanied with the degeneration of dopaminergic neurons in the central and peripheral nervous system. The diagnosis of Parkinson's disease can still be made only on the stage of irreversible and nearly total degeneration of the nigrostriatum dopaminergic system and exhaustion of brain compensatory mechanisms that explains the low efficacy of therapy. Ophthalmic pathology is one of the nonmotor symptoms of Parkinson's disease. This can be explained firstly by the fact that eye is a 'peripheral part of brain' and secondly by the involvement of dopaminergic neurons (dopamine-producing cells) that are subject to the selective degeneration during Parkinson's disease in the regulation of visual function in the eye and brain. Dopaminergic neurons and dopamine receptors are present in all structures of the eye. Parkinson's disease cause abnormalities not only in the retina but in the whole optic tract and can be considered as peripheral manifestations of the disease that precede the well-known motor dysfunctions. This review describes ophthalmological symptoms of Parkinson's disease, possible pathophysiological mechanisms of their development, optical disorders in experimental models of Parkinson's disease and also the perspectives of experimental and clinical studies of visual disorders for the development of preclinical diagnosis of Parkinson's disease.

[Novel agonists of melatonin receptors as promising hypotensive and neuroprotective agents for therapy of glaucoma]. / Novye agonisty melatoninovykh retseptorov kak perspektivnye gipotenzivnye i neiroprotektornye sredstva dlia terapii glaukomy.

Melatonin is a pineal hormone that has a capacity to lower intraocular pressure; it exhibits neuroprotective and antioxidant properties that make it possible to use melatonin in the therapy of glaucoma. Analogs of melatonin having affinity to melatonin receptors are promising candidates for application as antiglaucomatous drugs. Chemical modification of the melatonin structure can in-crease efficiency, bioavailability and selectivity of these analogs. We have designed and synthe-sized a number of new 2-oxindole derivatives - ligands of melatonin MT3 subtype receptors that displayed ability to lower intraocular pressure in normotensive rabbits and high antioxidant activity against hydroxyl radical and superoxide anion-radical. The antioxidant activity of new ligands was several times higher than one of melatonin that makes them prospective therapeutic tools for the diseases that include oxidative stress. The maximal hypotensive effect of analogs was comparable to that of melatonin itself but prolonged. Combination of these properties gives an opportunity of using the presented melatonin analogs in complex therapy of glaucoma.

[Effect of melatonin instillations on the clinical course of experimental uveitis and biochemical processes in tears and aqueous humor].

Acute immunogenic uveitis was modeled in rabbits via the subcutaneous and intravitreal injections of normal horse serum. We studied the effect of instillations of 0.1% melatonin solution on the clinical course of uveitis and biochemical parameters of tear fluid and aqueous humor: antioxi-dant activity, protein concentration and α(2)-macroglobulin level. Melatonin instillations decreased clinical manifestations of uveitis. We found that the antioxidant activity in tears of the rabbits treated with melatonin was substantially higher and the α(2)-macroglobulin level lower than in untreated animals. Antioxidant activity in aqueous humor taken on day 10 of uveitis was also twice higher while protein and α(2)-macroglobulin levels were 1.5-2 times lower than in untreated animals. These data indicate that instillations of melatonin increase the local antioxidant activity and decrease the acuity of inflammation and permeability of hematoophthalmic barrier in uveitis.

[Melatonin as a new promising agent for the treatment and prevention of retinopathy of prematurity]. / Eksperimental'noe issledovanie vozmozhnosti primeneniya melatonina v lechenii i profilaktike retinopatii nedonoshennykh.

AIM: To evaluate the effect of exogenous melatonin on the blood-retinal barrier and oxidative status of the vitreous in rats with oxygen-induced retinopathy (OIR) and analyze its prospects in the treatment and prevention of retinopathy of prematurity (ROP). MATERIAL AND METHODS: The study was performed on 48 Wistar rat pups (96 eyes) divided into 4 groups 12 animals each: OIR group, melatonin group and two control groups. In order to induce retinopathy, rat pups and does were placed in an incubator for 14 days after birth. Oxygen concentration in the incubator changed from 60 to 15% every 12 hours. The controls for this experiment were rats that grew under normoxic conditions (21%). The two other groups of rats were injected with 30 ml intraperitoneal melatonin (Sigma-Aldrich) in sterile 0.05 M phosphate buffer (pH 7.4) at a dose of 10 mg/kg for 14 days starting on day 1. The pups were killed on days 7 (n=16), 14 (n=16), and 18 (n=16). Binocular enucleation was performed in all cases. The total protein level and antioxidative activity (AOA) were then measured in vitreous samples. RESULTS: Oxygen-induced retinopathy had two phases and was accompanied by a sharp increase in the vitreal AOA and total protein. After intraperitoneal melatonin injections made during the period of early OIR-associated vascular changes, the said parameters were decreased down to near-control values at any times during the follow-up period. CONCLUSION: Exogenous melatonin, due to its strong antiangiogenic and antioxidant activity, helps stabilize the blood-retinal barrier in OIR.

[Effects of dexamethasone and superoxide dismutase instillations on clinical course of uveitis and local biochemical processes (experimental study)].

AIM: to evaluate and compare the effect of topical superoxide dismutase (SOD), which is an antioxidant enzyme, dexamethasone, and a combination of these on the course of experimental uveitis in rabbits as well as biochemical parameters of aqueous and vitreous humor. MATERIAL AND METHODS: Acute uveitis was induced in 16 rabbits by a double injection (subcutaneous and intravitreal) of normal horse serum. Of them 12 animals, divided into 3 groups of 4 each, received topical SOD, dexamethasone, or both daily for 7 days. The remaining 4 rabbits (8 eyes) were treated with placebo and, thus, constituted the control group. On day 8 the following parameters were measured in aqueous humor: protein concentration, antioxidant activity, SOD activity, α2-macroglobulin level, and leukocyte number. Total protein and albumin levels in vitreous humor were also determined. RESULTS: The effects of SOD and dexamethasone instillations were considered similar in many parameters. However, SOD was associated with a greater increase in antioxidant activity and a greater decrease in aqueous humor leukocytes, while dexamethasone was more effective in decreasing aqueous humor α2-macroglobulin and vitreous humor protein and albumin. The substances had a synergistic effect on iridal edema as well as aqueous humor leukocyte number and α2-macroglobulin level. CONCLUSION. Adding SOD to the complex therapy of uveitis results in lower inflammation intensity and enhanced dexamethasone effect.

Effects of hydroxypyridine derivatives mexidol and emoxypin on the reparative processes in rabbit eye on the models of corneal epithelial defect and conjunctival ischemia.

Deepithelialization of the cornea (diameter 7 mm) was performed in rabbits and the rate of defect epithelialization was evaluated. Conjunctival ischemia was modeled by application of graduated alkaline burn. Antioxidant activity and content of nitrates and nitrites was measured in the tear fluid before and after burn by chemiluminescence and Griess methods, respectively. Emoxypin and mexidol promoted healing of corneal epithelial defect at the stage of epitheliocyte migration to the defect area and at the stage of their proliferation, respectively. After treatment with both agents, the area of conjunctival ischemia decreased more rapidly, but the efficiency of mexidol was higher. Antioxidant activity and content of products of NO metabolism in tear fluid decreased after burn. Mexidol, but not emoxypin, increased these parameters. Thus, mexidol and emoxypin have different effects on corneal epithelialization and conjunctival ischemia and effects of mexidol are more pronounced.

[Oxidative stress in uveitis and its correction with superoxide dismutase antioxidative enzyme (experimental study)].

OBJECTIVE: to study the influence of experimental uveitis on those biochemical parameters of aqueous humor that reflect inflammation acuity as well as local antioxidant and local antiproteolytic activity; to study the effect of topical superoxide dismutase (SOD) on the clinical course of uveitis and ocular metabolism. MATERIAL AND METHODS: Acute uveitis was induced in rabbits by a double injection (subcutaneous and intravitreal) of normal horse serum. The following parameters of aqueous humor were measured: protein concentration, antioxidant activity, SOD activity, alpha2-macroglobulin level, total nitrates and nitrites, and leukocyte number. Clinical assessment and histopathological study were performed. RESULTS: It was found that uveitis is associated with a statistically significant increase in protein concentration, leukocyte number, SOD activity, and alpha2-macroglobulin level in aqueous humor as well as a decrease in anti-hydroxyl radical activity. SOD instillations contributed to the reduction of the listed parameters and improvement of the antioxidant activity. Clinical presentations of uveitis also became less pronounced. CONCLUSION: SOD instillations for oxidative stress correction help reduce clinical presentations of uveitis, which is confirmed by biochemical examination.

[Level of tear endothelin-1 and plasminogen in patients with glaucoma and proliferative diabetic retinopathy].

A considerable tear endothelin-1 increase (2-3 times) has been found in patients with primary open-angle glaucoma and proliferative diabetic retinopathy. Patients with proliferative retinopathy also showed an increase of plasminogen level in tear fluid and a tendency of a similar increase in blood serum. No correlation between endothelin-1 and plasminogen levels in these pathologies was established. Tear endothelin-1 and plasminogen measurement could be used as an informative and non-invasive method to help prognosis making, condition severity evaluation and control the effectiveness of treatment of ocular local microcirculatory disturbances.