RESUMO
We conducted a study on the impact of intraperitoneal injections of melatonin and its three bioisosteres (compounds 1-3) on the development of oxygen-induced retinopathy in newborn rats during a 21-day experiment. It was demonstrated that melatonin and its analogues 1-3 effectively reduce the total protein concentration in the vitreous body of rat pups, decrease concentration of VEGF-A, and lower the level of oxidative stress (as indicated by normalization of antioxidant activity in the vitreous body). Melatonin and its analogues 1-3 equally normalize the level of VEGF-A. Analogues 1 and 2 even exceed melatonin in their ability to reduce protein influx into the vitreous body. However, analogue 2 had no effect on antioxidant activity, while analogues 1 and 3 caused a significant increase in this parameter, with analogue 3 even slightly exceeding melatonin. Thus, it can be concluded that analogues 1-3 are comparable to melatonin and can be utilized as potential therapeutic agents for the treatment of retinopathy of prematurity.
Assuntos
Melatonina , Retinopatia da Prematuridade , Ratos , Animais , Melatonina/farmacologia , Melatonina/uso terapêutico , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Modelos Animais de DoençasRESUMO
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.
Assuntos
Oftalmopatias Hereditárias , Doenças Retinianas , Humanos , Vitreorretinopatias Exsudativas Familiares/genética , Endotelina-1/genética , Oftalmopatias Hereditárias/diagnóstico , Oftalmopatias Hereditárias/genética , Mutação , LinhagemRESUMO
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.
Assuntos
Enalaprilato , Retinopatia da Prematuridade , Humanos , Recém-Nascido , Ratos , Animais , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/prevenção & controle , Ratos Wistar , Angiotensina IIRESUMO
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.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Degeneração Macular , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , Inflamação , Macroglobulinas , Degeneração Macular/diagnóstico , Degeneração Macular/etiologia , Retina , Soro/metabolismoRESUMO
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.
Assuntos
Células-Tronco Pluripotentes Induzidas , Epitélio Pigmentado da Retina , Coelhos , Animais , Endotelina-1 , Tomografia de Coerência ÓpticaRESUMO
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.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Adulto , Angiotensinas , Bradicinina , Retinopatia Diabética/diagnóstico , Humanos , Edema Macular/diagnóstico , Projetos Piloto , PrognósticoRESUMO
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.
Assuntos
Melatonina , Neovascularização Retiniana , Retinopatia da Prematuridade , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Humanos , Recém-Nascido , Melatonina/farmacologia , Ratos , Ratos Wistar , Retina , Retinopatia da Prematuridade/etiologia , Retinopatia da Prematuridade/prevenção & controleRESUMO
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.
Assuntos
Retinopatia Diabética , Endotelinas/metabolismo , Glaucoma , Endotelina-1 , Humanos , Retina , Vasos RetinianosRESUMO
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.
Assuntos
Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Angiotensinas/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Humanos , Edema Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Soro , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
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.
Assuntos
Antioxidantes/farmacologia , Glaucoma/prevenção & controle , Pressão Intraocular/efeitos dos fármacos , Melatonina/farmacologia , Fármacos Neuroprotetores/farmacologia , Hipertensão Ocular/tratamento farmacológico , Receptores de Melatonina/agonistas , Animais , Antioxidantes/síntese química , Desenho de Fármacos , Expressão Gênica , Glaucoma/metabolismo , Glaucoma/fisiopatologia , Indóis/química , Ligantes , Masculino , Melatonina/análogos & derivados , Melatonina/síntese química , Fármacos Neuroprotetores/síntese química , Hipertensão Ocular/metabolismo , Hipertensão Ocular/fisiopatologia , Oxirredução , Oxindóis , Estudos Prospectivos , Ligação Proteica , Coelhos , Receptores de Melatonina/genética , Receptores de Melatonina/metabolismo , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Humor Aquoso/efeitos dos fármacos , Melatonina/farmacologia , Lágrimas/efeitos dos fármacos , Uveíte/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Humor Aquoso/metabolismo , Modelos Animais de Doenças , Masculino , Coelhos , Superóxido Dismutase/metabolismo , Lágrimas/metabolismo , Uveíte/metabolismo , Uveíte/fisiopatologia , alfa-Macroglobulinas/metabolismoRESUMO
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.
Assuntos
Melatonina/farmacologia , Retinopatia da Prematuridade/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Retinopatia da Prematuridade/metabolismo , Resultado do Tratamento , Corpo Vítreo/efeitos dos fármacosRESUMO
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.
Assuntos
Humor Aquoso/metabolismo , Dexametasona/administração & dosagem , Superóxido Dismutase/administração & dosagem , Uveíte/tratamento farmacológico , Animais , Humor Aquoso/efeitos dos fármacos , Fenômenos Bioquímicos/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada , Sequestradores de Radicais Livres/administração & dosagem , Glucocorticoides/administração & dosagem , Instilação de Medicamentos , Coelhos , Uveíte/diagnóstico , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/metabolismoRESUMO
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.
Assuntos
Túnica Conjuntiva/patologia , Córnea/patologia , Queimaduras Oculares/tratamento farmacológico , Isquemia/tratamento farmacológico , Picolinas/uso terapêutico , Piridinas/uso terapêutico , Animais , Túnica Conjuntiva/efeitos dos fármacos , Córnea/efeitos dos fármacos , Queimaduras Oculares/induzido quimicamente , Isquemia/metabolismo , Masculino , Picolinas/farmacologia , Piridinas/farmacologia , Coelhos , Cicatrização/efeitos dos fármacosRESUMO
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.
Assuntos
Biomarcadores/metabolismo , Superóxido Dismutase , Uveíte , alfa-Macroglobulinas/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Humor Aquoso/metabolismo , Córnea/patologia , Modelos Animais de Doenças , Estresse Oxidativo , Coelhos , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Resultado do Tratamento , Uveíte/tratamento farmacológico , Uveíte/metabolismo , Uveíte/patologiaRESUMO
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.
Assuntos
Retinopatia Diabética/metabolismo , Endotelina-1/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Plasminogênio/metabolismo , Lágrimas/química , Vitreorretinopatia Proliferativa/metabolismo , Idoso , Biomarcadores/metabolismo , Retinopatia Diabética/fisiopatologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Microcirculação , Índice de Gravidade de Doença , Vitreorretinopatia Proliferativa/fisiopatologiaRESUMO
Methodology for production of calcium-phosphate nanoparticles is developed and its efficacy as a drug carrier system is estimated by example of timolol. Conditions for production of particles with optimal size and resistance are determined, methodology of loading of particles with timolol is developed. Physical parameters of particles (form, size, relief), kinetics of saturation with drug and its release are studied. Packaging of timolol into calcium phosphate nanoparticles was showed to enhance and prolong its hypotensive effect in experiment on healthy rabbits.
Assuntos
Fosfatos de Cálcio , Sistemas de Liberação de Medicamentos/métodos , Pressão Intraocular/efeitos dos fármacos , Nanopartículas/química , Timolol/administração & dosagem , Administração Oftálmica , Animais , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Nanotecnologia , Coelhos , Tecnologia Farmacêutica/métodos , Timolol/farmacocinética , Resultado do TratamentoRESUMO
Increased plasminogen level in tear fluid was found within 28 days and increased plasmin activity in 1-3 and 21 days after alkali burn of cornea, this is the time of cornel ulcers development. Increased plasminogen level and plasmin activity in cornea, conjunctiva and intraocular fluid was found in three days after trauma. Subconjunctival injections of angiostatin K1-4,5 (a product of plasminogen metabolism) during 3 weeks resulted in significant suppression of corneal neovascularization within 14 days and of active branching of the vessels in the following. The use of angiostatin reduced depth and area of corneal ulcers. Obtained data shows the promising potential of development of medications based on angiostatin K1-4,5 for suppression of corneal neovascularization and for treatment of diseases associated with corneal ulceration.
Assuntos
Angiostatinas , Córnea/metabolismo , Neovascularização da Córnea/metabolismo , Úlcera da Córnea , Queimaduras Oculares , Neovascularização Patológica/metabolismo , Fluxo Sanguíneo Regional/efeitos dos fármacos , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/metabolismo , Inibidores da Angiogênese/farmacologia , Angiostatinas/administração & dosagem , Angiostatinas/metabolismo , Angiostatinas/farmacologia , Animais , Humor Aquoso/metabolismo , Túnica Conjuntiva/metabolismo , Córnea/irrigação sanguínea , Córnea/fisiopatologia , Neovascularização da Córnea/etiologia , Neovascularização da Córnea/fisiopatologia , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/etiologia , Úlcera da Córnea/metabolismo , Úlcera da Córnea/fisiopatologia , Descoberta de Drogas , Queimaduras Oculares/induzido quimicamente , Queimaduras Oculares/complicações , Queimaduras Oculares/fisiopatologia , Modelos Animais , Neovascularização Patológica/etiologia , Neovascularização Patológica/fisiopatologia , Plasminogênio/metabolismo , CoelhosRESUMO
The authors have evaluated the local renin-angiotensin system on a model of experimental postburn conjunctival ischemia from the tear activity of angiotensin-converting enzyme (ACE) and studied whether impaired microcirculation might be restored by locally applying the ACE inhibitor captopril. It has been found that in conjunctival ischemia, there is a considerable increase in the activity of ACE, the key enzyme of the renin-angiotensin system, the activity of which largely determines the microcirculation in eye tissues. Instillations of the ACE inhibitor to rabbits within 2 weeks after alkaline burn of the eye result in a reduction in ACE activity and an earlier recovery of microcirculation in the area of conjunctival ischemia. Instillations of the ACE inhibitor captopril in ocular burn facilitate the maintenance of the tear antioxidant potential at the high level, which also suggests that the ACE inhibitor has a positive effect on the course of reparative processes after ocular burn injury. The findings suggest that it is promising to locally use ACE inhibitors for the treatment of ischemic processes in the eye.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Queimaduras Químicas/tratamento farmacológico , Captopril/uso terapêutico , Túnica Conjuntiva/irrigação sanguínea , Queimaduras Oculares/tratamento farmacológico , Isquemia/tratamento farmacológico , Álcalis , Animais , Modelos Animais de Doenças , Queimaduras Oculares/induzido quimicamente , Seguimentos , Microcirculação , Peptidil Dipeptidase A/metabolismo , Coelhos , Lágrimas/enzimologia , Fatores de Tempo , Resultado do TratamentoRESUMO
A rabbit model of deep alkaline-induced corneal burn was used to study the involvement of the local renin-angiotensin system of the eye in the development of an inflammatory process and wound healing. Corneal burn injury was shown to cause a significant increase in the activity of angiotensin-converting enzyme (ACE) in the tear and internal ocular tissue structures, promoting their microcirculatory disorders and inflammation development. The local use of ACE inhibitors as instillations substantially reduces an inflammatory reaction and the incidence of deep and extensive corneal ulcers. The study performed provides experimental rationale for the local use of ACE inhibitors for the treatment of inflammatory processes in the eye.