Carnosine supplementation and retinal oxidative parameters in a high-calorie diet rat model.

BACKGROUND: To assess oxidative effects induced by a high-calorie diet on the retina of Wistar rats and test the antioxidative effects of carnosine supplementation. METHODS: Wistar rats were randomly divided into the following groups: standard diet (SD), high-calorie diet (HcD), standard diet + carnosine (SD + Car), and high-calorie diet + carnosine (HcD + Car). The body weight, adiposity index, plasma glucose, total lipids, high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid, creatinine, and triglycerides of the animals were evaluated. The retinas were analyzed for markers of oxidative stress. Hydrogen peroxide production was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCF) oxidation. The total glutathione (tGSH), total antioxidant capacity (TAC), protein carbonyl, and sulfhydryl groups of the antioxidant system were analyzed. RESULTS: TAC levels increased in the retinas of the SD + Car group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the HcD group (p < 0.05). The levels of GSH and the GSSH:GSSG ratio were increased in the HcD + Car group compared to the SD + Car group (p < 0.05). An increase in the retinal carbonyl content was observed in the HcD group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the SD + Car group (p < 0.05). A high-calorie diet (HcD) was also associated with a decrease in retinal sulfhydryl-type levels compared to the SD group (p < 0.05). CONCLUSION: The results suggest that feeding a high-calorie diet to rats can promote an increase in carbonyl content and a reduction in sulfhydryl groups in their retinas. The administration of carnosine was not effective in attenuating these oxidative markers. TRIAL REGISTRATION: Animal Ethics Committee of Botucatu Medical School - Certificate number 1292/2019.

Effect of flaxseed on choroid-sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits.

The aim of the present study was to evaluate the effect of flaxseed on choroid-sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits. New Zealand male albino rabbits (n 21) were divided into two groups: group 1 (G1; n 11), fed a hypercholesterolaemic diet, and group 2 (G2; n 10), fed a hypercholesterolaemic diet enriched with flaxseed flour. The serum concentrations of total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol, TAG and fasting blood glucose were determined at the start of the experiment and on the day of killing (8th week). Choroid and sclera samples were subjected to haematoxylin-eosin (HE) staining and histomorphometric and immunohistochemical analyses with the anti-oxidised LDL antibody. Sensory retina samples were subjected to an immunohistochemical analysis with the primary monoclonal nitrotyrosine antibody. At the end of the experiment, a significant increase was observed in TC and LDL-C concentrations in G1 rabbits when compared with G2 rabbits (P= 0·008 and P= 0·02, respectively). HE staining revealed a significant increase in choroid-sclera complex thickness in G1 rabbits when compared with G2 rabbits (P< 0·001). Immunohistochemical analysis of choroid and sclera samples with the anti-oxidised LDL marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P< 0·001). Immunohistochemical analysis of sensory retina samples with the anti-nitrotyrosine marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P= 0·002). Flaxseed reduced the choroid-sclera complex thickness of diet-induced hypercholesterolaemic rabbits and the expression of oxidised LDL in the choroid-sclera complex as well as the expression of nitrotyrosine in the sensory retina.

The nuclear factor E2-related factor 2 and age-related macular degeneration.

After the discovery of anti-vascular endothelial growth factor agents as treatment of wet age-related macular degeneration, the number of studies with the objective to understand the molecular mechanisms involved in the age-re lated macular degeneration genesis has increased. The importance of the nuclear factor e2-related factor 2 lies in its activation-derived proteins being involved in the maintenance of the redox balance and consequent prevention of degenerative macular disease. This article aims to present the characteristics of nuclear factor e2-related factor 2 and describe the main nuclear factor e2-related factor 2-activated antioxidant enzymes that contribute to the preservation of vision.

The nuclear factor E2-related factor 2 and age-related macular degeneration / O fator 2 relacionado a NF-E2 e a degeneração macular relacionada à idade

ABSTRACT After the discovery of anti-vascular endothelial growth factor agents as treatment of wet age-related macular degeneration, the number of studies with the objective to understand the molecular mechanisms involved in the age-re lated macular degeneration genesis has increased. The importance of the nuclear factor e2-related factor 2 lies in its activation-derived proteins being involved in the maintenance of the redox balance and consequent prevention of degenerative macular disease. This article aims to present the characteristics of nuclear factor e2-related factor 2 and describe the main nuclear factor e2-related factor 2-activated antioxidant enzymes that contribute to the preservation of vision.

RESUMO Após a descoberta do anti fator de crescimento en dotelial vascular no tratamento da degeneração macular relacionada à idade úmida, muitas pesquisas têm sido realizadas com o intuito de elucidar os mecanismos moleculares envolvidos na gênese da degeneração macular relacionada à idade. O fator nuclear eritroide 2 relacionado ao fator 2 destaca-se pelo fato de diversas proteínas, oriundas de sua ativação, estarem envolvidas na manutenção do equilíbrio do estado redox e consequente prevenção da doença macular degenerativa. Este artigo mostra as características do fator nuclear eritroide 2 relacionado ao fator 2 e descreve as principais enzimas antioxidantes originadas da ativação que contribuem para a preservação da visão.

[Angiography: safety x economy]. / Angiografia: segurança x economia.

PURPOSE: To evaluate the safety, effectiveness, and cost of angiofluoresceinographic examination by using both the least amount of dye as well as digital equipment along with a laser photocopier. METHODS: Prospective and comparative study carried out in a group of 70 patients, who underwent an angiographic evaluation with a conventional retinographer injecting 5 ml sodium fluorescein at 10% (control group) as well as a group of 70 patients who underwent an angiographic evaluation with a digital retinographer injecting 2 ml fluorescein at 10% (study group). Arterial pressure, heart rate and oximetry were assessed prior to and after the dye injection. Organic reactions related to the examination were reported. Photograph quality as well as cost between the two techniques were compared. RESULTS: Control group patients showed a greater increase in systolic and diastolic arterial pressure. Heart rate, oximetry measurement and adverse reactions did not show any significant statistical differences between both groups. As for the quality of photographs, a better performance was noticed in the control group. As for the cost, the examination carried out in the study group required lower cost and thus saved around 54.8% per examination in relation to the control group. CONCLUSION: The examination carried out with a lower dose of fluorescein using digital equipment along with a laser photocopier provided greater stability in the systolic and diastolic arterial pressure. However, it did not have any influence on heart rate, oximetry or adverse reactions such as nausea, vomiting, syncope and rashes. The quality of photographs was poor although they enabled diagnosis as well as therapy follow-up for those who carried out the examination. Moreover, economically the above procedure represented a gain of 66.26%, against 25.81% in relation to the conventional equipment.

[Combined central retinal vein and artery occlusion after retrobulbar anesthesia--report of two cases]. / Oclusão artério-venosa da retina após bloqueio retrobulbar--relato de dois casos.

Two cases of combined central retinal artery and vein occlusion after intraocular surgery are described. Both patients were submitted to peribulbar anesthesia. Due to the painful sensation and ocular mobility retrobulbar anesthesia was necessary. At the end of the surgery both patients received a subconjunctival injection of gentamicin associated with dexamethasone. On the very first day after the surgery the two patients showed pupillary areflexia and visual acuity of luminous perception when they were referred to our service. The confirmation of the diagnosis of combined vascular occlusion of the retina was obtained by fluorescein angiography test. The two patients never showed, any neurological alteration. However visual loss was severe and permanent. By means of surgical description, clinical history, fundus photography and fluorescein angiography we are able to discuss the possible causes of this severe retinal vascular injury emphasizing the presumed anesthesic injection that was given into the optical nerve during retrobulbar anesthesia. At the same time we discuss preventive measures to avoid such problem.

[Iris prosthesis in traumatic aniridia as an attempt to control refractory glaucoma induced by silicone oil in the anterior chamber: case report]. / Prótese de íris, na aniridia traumática, como tentativa de controlar glaucoma refratário provocado pela presença de óleo de silicone na câmara anterior: relato de caso.

The objective of this report is to demonstrate the effectiveness of an iris prosthesis to treat a refractory glaucoma induced by silicone oil in the anterior chamber. This case is about a patient who suffered a trauma caused by firearm shrapnel. A vitreous-retinal surgery was performed to remove intraocular foreign matter and to realign the retina that was detached. Due to the partial traumatic aniridia, silicone oil that was introduced in the vitreous chamber to keep the retina in place migrated to the anterior chamber, resulting in the decrease of endothelium cells and uncontrollable intraocular pressure. We performed transscleral fixation of the iris prosthesis to correct these problems. After a 45-month period of evolution, sight became stable at the 1 meter finger-count distance and intra-ocular pressure at 14 mmHg We may conclude that the triad that consists of lack of: iris diaphragm, aphakia and silicone oil that could not be removed because of inexorable occurrence of detachment of the retina should lead the surgeon to consider transscleral fixation of the iris prosthesis. This procedure might control intraocular pressure and/or preserve corneal transparency, preventing silicone oil from contact with the trabecular net and the corneal endothelium.

Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits.

PURPOSE: This study aimed to evaluate the expression of the inflammatory cytokines TNF-α and IL-6 in the sclera and choroid of hypercholesterolemic rabbits. METHOD: Twenty-one New Zealand male albino rabbits were divided into two groups: NG and HG. The NG group was fed a standard rabbit diet and the HG group was fed a cholesterol-enriched diet (1%). The serum total cholesterol, triglyceride, HDL cholesterol, and fasting blood glucose levels were determined at the beginning of the experiment and on the day of euthanasia. Euthanasia of animals in the NG and HG groups was performed at the end of the 4th and 8th week, respectively. The eyes were analyzed immunohistochemically using TNF-α and IL-6 antibodies. RESULTS: At the time of euthanasia, the HG group showed a significant increase in total cholesterol and triglyceride when compared with the NG group (p<0.001). When compared with the NG group, there was a significant increase in the expression of TNF-α (p<0.001) and IL-6 (p=0.002) in the choroid and sclera of animals in the HG group. CONCLUSION: This study demonstrates that the hypercholesterolemic diet induces expression of TNF-α and IL-6 in the choroid and sclera of rabbits.

Effect of candesartan on the expression of sclera-choroidal intercellular adhesion molecule-1 in hypercholesterolemic models.

OBJECTIVE: To evaluate the effect of blocking the angiotensin II AT-1 receptor by the systemic administration of candesartan on the expression of intercellular adhesion molecule-1 in the sclera and choroid of hypercholesterolemic rabbits. METHODS: New Zealand rabbits were divided into 3 groups, as follows: GI, which was fed a rabbit standard diet; GII, which was fed a hypercholesterolemic diet; and GIII, which received hypercholesterolemic diet plus candesartan. Samples of the rabbits' sclera and choroid were then studied by hematoxylin-eosin staining and histomorphometric and immunohistochemical analyses for intercellular adhesion molecule-1 expression. RESULTS: Histological analysis of hematoxylin- and eosin-stained sclera and choroid revealed that macrophages were rarely present in GI, and GII had significantly increased macrophage numbers compared to GIII. Moreover, in GII, the sclera and choroid morphometry showed a significant increase in thickness in comparison to GI and GIII. GIII presented a significant increase in thickness in relation to GI. Sclera and choroid immunohistochemical analysis for intercellular adhesion molecule-1 expression revealed a significant increase in immunoreactivity in GII in relation to GI and GIII. GIII showed a significant increase in immunoreactivity in relation to GI. CONCLUSION: Candesartan reduced the expression of intercellular adhesion molecule-1 and consequently macrophage accumulation in the sclera and choroid of hypercholesterolemic rabbits.

Effect of olmesartan on leukocyte recruitment in choroid-sclera complex in hypercholesterolemia model.

PURPOSE: Demonstrate that the blockade of angiotensin II AT-1 receptors, through the systemic administration of olmesartan, can reduce the MCP-1 expression and the resulting macrophage accumulation in the choroid and sclera of hypercholesterolemic rabbits. METHODS: Thirty-two New Zealand rabbits were divided into 3 groups: group I (GI) was fed a standard rabbit diet; group II (GII) was fed a hypercholesterolemic diet; and group III (GIII) was fed a hypercholesterolemic diet plus olmesartan. Serum levels of total cholesterol, triglyceride, HDL cholesterol, and blood glucose were determined in fasting rabbits at the beginning of the experiment and on the day of euthanasia. The choroid and sclera were submitted to morphometric analysis as well as immunohistochemical analysis with MCP-1 and RAM-11 (macrophage marker) antibodies. RESULTS: No abnormality was detected in GI. Group II and III had significant increases in choroid-sclera complex thicknesses when compared with group I (P<0.001). GII showed a significant increase in immunoreactivity for MCP-1 in relation to GI (P=0.001) and GIII (P=0.004). GII showed a significant increase in immunoreactivity for RAM-11 of the choroid-sclera complex in relation to GI (P<0.001) and GIII (P=0.034). A significant increase in immunoreactivity for RAM-11 was observed in GIII in relation to GI (P=0.008). CONCLUSION: Olmesartan reduced the MCP-1 expression and the resultant macrophage accumulation in the choroid-sclera complex of hypercholesterolemic rabbits.

[Increased VEGFR-1 immunoreactivity in the choroid-scleral complex in hypercholesterolemia experimental model]. / Aumento da imunorreatividade ao VEGFR-1 no complexo coroido-escleral em modelo experimental de hipercolesterolemia.

PURPOSE: The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF) in the choroid and sclera using hypercholesterolemia experimental model. METHODS: New Zealand rabbits were divided into two groups: 8 rabbits (8 eyes), in the normal diet group (NG), were fed by a standard diet for 4 weeks; and 13 rabbits (13 eyes), in the hypercholesterolemic group (HG), were fed by a 1% cholesterol-enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the initiation of the experiment and at the euthanasia time. After hypercholesterolemic group 8th week and NG 4th week, animals were euthanized and their eyes underwent immunohistochemical analysis with the RAM-11 and VEGFR-1). RESULTS: The diet has induced a significant increase in total cholesterol and triglyceride levels in HG when compared with NG (p<0.001). There was a significant increase in the RAM-11 and VEGFR-1 expressions in hypercholesterolemic group choroid and sclera in relation to NG (p<0,001). CONCLUSION: This study has revealed that the hypercholesterolemic diet in rabbits induces an increase in the macrophage concentration and immunoreactivity to VEGFR-1 in the choroid and sclera, resembling human age-related macular degeneration (ARMD).

[Increase of choroidal and scleral MCP-1 expression in hypercholesterolemia experimental model]. / Aumento da expressão do MCP-1 coroidal e escleral em modelo experimental de hipercolesterolemia.

PURPOSE: The aim of this study is to experientially demonstrate that a cholesterol-enriched diet induces an increase in the MCP-1 expression in the choroid and sclera. METHOD: New Zealand rabbits were divided into two groups: GN (normal diet group) of 8 rabbits (8 eyes) was fed a standard rabbit diet for 4 weeks; GH (hypercholesterolemic group) of 13 rabbits (13 eyes) was fed a 1% cholesterol enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the start of the experiment and at the euthanasia time. After GH 8th week and GN 4th week animals were euthanized and their eyes underwent immunohistochemical analysis with the anti-MCP-1 antibody. RESULTS: The diet has induced a significant increase in GH total cholesterol and triglyceride levels when compared with NG (p<0.001). There was a significant increase in the MCP-1 expression in GH choroid and sclera in relation to GN (p<0.001). CONCLUSION: This study has revealed that the hypercholesterolemic diet in rabbits induces an increase in the MCP-1 expression in the choroid and sclera.

Sclerochorioretinal abnormalities in hypercholesterolemic rabbits treated with rosiglitazone.

BACKGROUND AND OBJECTIVE: To evaluate early retinal, choroidal, and scleral abnormalities induced by a hypercholesterolemic diet and the prevention of these abnormalities after oral administration of rosiglitazone in rabbits. MATERIALS AND METHODS: Fifty-four New Zealand rabbits were divided into four study groups: control group, normal diet; group 1, hypercholesterolemic diet; group 2, hypercholesterolemic diet associated with daily administration of 3 mg of rosiglitazone from day 14 after beginning the diet; and group 3, hypercholesterolemic diet associated with daily administration of 3 mg of rosiglitazone since the beginning of the experiment. Sclera and choroid underwent histologic and histomorphometric analyses. Retina underwent immunohistochemical analysis with anti-calretinin and anti-glial fibrillary acidic protein (GFAP) antibodies. RESULTS: No abnormalities were observed in the control group. Group 1 had significant increases in scleral and choroidal thicknesses compared with the control group (P < .01) and group 3 (P < .05). Group 1 presented significant increases in immunoreactivity (P < .001) to the anti-calretinin antibody compared with the other groups. Groups 2 and 3 had significant (P < .002) increases in calretinin immunoreactivity compared with the control group. GFAP was negative in all groups. CONCLUSION: The hypercholesterolemic diet induced early retinal, choroidal, and scleral abnormalities. Rosiglitazone preserved the structural anatomy.

[Evaluation of choroid and sclera early alterations in hypercholesterolemic rabbits: histologic and histomorphometric study]. / Avaliação das alterações precoces na coróide e esclera ocorridas em coelhos hipercolesterolêmicos: estudo histológico e histomorfométrico.

PURPOSE: To demonstrate experimentally, by means of histological and histomorphometric examinations, the sclera and choroid degenerative alterations, which take place at an early stage due to a hypercholesterolemic diet. METHODS: New Zealand rabbits were divided into two groups: CG (control group) of 6 rabbits (6 eyes) received a regular diet for 6 weeks; G1, of 12 rabbits (12 eyes), was first fed a 1% cholesterol diet (Sigma-Aldrich) for 2 weeks and then from the 14th day on a 0.5% cholesterol diet (Sigma-Aldrich). The eyes underwent a histological analysis, stained with hematoxiline-eosine, and a morphometric examination. The histomorphometric analysis was performed in the posterior region, adjacent to the optic disk, and in the peripheral region. RESULTS: The CG presented a mean sclera and choroid thickness of 228.61 +/- 31.71 micrometers in the peripheral region, while the thickness in the posterior region was approximately 246.07 +/- 25.66 micrometers. In G1, these values were 303.56 +/- 44.21 micrometers in the peripheral region and 295.59 +/- 62.59 in the posterior region. There was a statistically significant difference in the sclera and choroid thickness between the groups in the peripheral region (p<0.001); however, this difference did not occur in the posterior region (p=0.250). The large number of histiocytes and collagen fibers accounted for the increase of G1 wall thickness in relation to CG. CONCLUSION: This study demonstrated that the hypercholesterolemic diet in rabbits induces a fast increase in the choroid and sclera thickness, mainly due to the increase in the number of histiocytes and collagen fibers.

Evaluation of early abnormalities of the sensory retina in a hypercholesterolemia experimental model: an immunohistochemical study.

PURPOSE: The aim of this study is to demonstrate the early changes of the sensory retina induced by hypercholesterolemia in an experimental model. METHODS: New Zealand rabbits were divided into two groups: CG (Control Group) was fed a normal diet for 6 weeks. G1 was initially fed a 1% cholesterol diet for two weeks and from the 14th day on a 0.5% cholesterol diet until the 42nd day. The eyes underwent an immunohistochemical analysis with monoclonal antibodies anti-calretinin and anti-glial fibrillary acidic protein (GFAP). RESULTS: G1 cells and cell elements presented significant immunoreactivity to anti-calretinin. No immunoreactivity to anti-glial fibrillary acidic protein was observed in both groups. CONCLUSION: This study has shown that a hypercholesterolemic diet may induce early changes in the sensory retina in rabbits. The anti-calretinin monoclonal antibody was able to reveal calcium accumulation inside the nerve cells.

[Modifiable risk factors for age-related macular degeneration]. / Fatores modificáveis da degeneração macular relacionada à idade.

The authors present the main modifiable risk factors that may trigger and/or worsen age-related macular degeneration. Mechanisms of action related to these factors as well as preventive measures and intervention effectiveness are discussed.

Aumento da imunorreatividade da molécula de adesão intercelular-1 na esclera e coroide em modelo experimental de hipercolesterolemia / Increased intercellular adhesion molecule-1 immunoreactivity in the sclera-choroid complex in hypercholesterolemia experimental model

Objetivo: O objetivo deste trabalho é avaliar a expressão da molécula de adesão intercelular-1 (ICAM-1) na esclera e coroide de coelhos hipercolesterolêmicos. Métodos: Coelhos New Zealand foram organizados em dois grupos: GN (grupo dieta normal), composto por 8 coelhos (8 olhos), recebeu ração padrão para coelhos, durante 4 semanas; GH (grupo hipercolesterolêmico), composto por 13 coelhos (13 olhos), recebeu dieta rica em colesterol a 1% por 8 semanas. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 4ª semana para o GN e 8ª semana para o GH foi realizada a eutanásia dos animais. Os olhos foram corados com hematoxilina-eosina e submetidos à análise histológica, histomorfométrica e imunohistoquímica com o anticorpo ICAM-1. Resultados: Observou-se significativo aumento do colesterol total e triglicerídeos do GH em relação ao GN (p<0,001). A avaliação histológica com hematoxilina eosina revelou grande quantidade de macrófagos no complexo esclero-coroidal do GH. No GH constatou-se significativo aumento da espessura da esclera e coroide em relação ao GN (p<0,001). Houve significativo aumento da expressão da ICAM-1 na esclera e coroide dos animais do GH em relação ao GN (p<0,001). Conclusão: Este estudo demonstra que a dieta hipercolesterolêmica induz ao aumento da expressão da ICAM-1 na esclera e coroide de coelhos. .

Objective: The aim of this study is to investigate the expression of the intercellular adhesion molecule 1 (ICAM-1) in the sclera and choroid of hypercholesterolemic rabbits Methods: New Zealand rabbits were divided into two groups: the normal diet group (NG), with 8 rabbits (8 eyes), was fed a standard rabbit diet for 4 weeks; the hypercholesterolemic group (HG), with 13 rabbits (13 eyes), was fed a 1% cholesterol- enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the start of the experiment and at the euthanasia time. HG and NG animals were euthanized after 8th week and 4th week, respectively. Their eyes were stained with hematoxylin-eosin and underwent histological, histomorphometric and immunohistochemical analyses with ICAM-1 antibody. Results: The diet has induced a significant increase in total cholesterol and triglyceride levels in HG when compared with NG (p<0.001). The histological analysis with hematoxylin-eosin revealed a large number of macrophages in the HG sclera-choroid complex. Moreover, a significant increase in the HG sclera and choroid thickness was observed in relation to NG (p<0.001). There was a significant increase in the ICAM-1 expression in HG sclera and choroid in relation to NG Conclusion: This study has revealed that the hypercholesterolemic diet induces an increase in the ICAM-1 expression in the rabbits’ sclera and choroid. .

Effect of candesartan on the expression of sclera-choroidal intercellular adhesion molecule-1 in hypercholesterolemic models

OBJECTIVE: To evaluate the effect of blocking the angiotensin II AT-1 receptor by the systemic administration of candesartan on the expression of intercellular adhesion molecule-1 in the sclera and choroid of hypercholesterolemic rabbits. METHODS: New Zealand rabbits were divided into 3 groups, as follows: GI, which was fed a rabbit standard diet; GII, which was fed a hypercholesterolemic diet; and GIII, which received hypercholesterolemic diet plus candesartan. Samples of the rabbits' sclera and choroid were then studied by hematoxylin-eosin staining and histomorphometric and immunohistochemical analyses for intercellular adhesion molecule-1 expression. RESULTS: Histological analysis of hematoxylin- and eosin-stained sclera and choroid revealed that macrophages were rarely present in GI, and GII had significantly increased macrophage numbers compared to GIII. Moreover, in GII, the sclera and choroid morphometry showed a significant increase in thickness in comparison to GI and GIII. GIII presented a significant increase in thickness in relation to GI. Sclera and choroid immunohistochemical analysis for intercellular adhesion molecule-1 expression revealed a significant increase in immunoreactivity in GII in relation to GI and GIII. GIII showed a significant increase in immunoreactivity in relation to GI. CONCLUSION: Candesartan reduced the expression of intercellular adhesion molecule-1 and consequently macrophage accumulation in the sclera and choroid of hypercholesterolemic rabbits. .

Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits / Expressão das citocinas TNF-α and IL-6 na coroide e esclera de coelhos hipercolesterolêmicos

Purpose: This study aimed to evaluate the expression of the inflammatory cytokines TNF-α and IL-6 in the sclera and choroid of hypercholesterolemic rabbits. Method: Twenty-one New Zealand male albino rabbits were divided into two groups: NG and HG. The NG group was fed a standard rabbit diet and the HG group was fed a cholesterol-enriched diet (1%). The serum total cholesterol, triglyceride, HDL cholesterol, and fasting blood glucose levels were determined at the beginning of the experiment and on the day of euthanasia. Euthanasia of animals in the NG and HG groups was performed at the end of the 4th and 8th week, respectively. The eyes were analyzed immunohistochemically using TNF-α and IL-6 antibodies. Results: At the time of euthanasia, the HG group showed a significant increase in total cholesterol and triglyceride when compared with the NG group (p<0.001). When compared with the NG group, there was a significant increase in the expression of TNF-α (p<0.001) and IL-6 (p=0.002) in the choroid and sclera of animals in the HG group. Conclusion: This study demonstrates that the hypercholesterolemic diet induces expression of TNF-α and IL-6 in the choroid and sclera of rabbits. .

Objetivo: Avaliar a expressão das citocinas inflamatórias TNF-α e IL-6 na esclera e coroide de coelhos hipercolesterolêmicos. Método: Coelhos New Zealand foram organizados em dois grupos: GN recebeu ração padrão para coelhos; GH recebeu dieta rica em colesterol a 1%. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 4ª semana para o GN e 8ª semana para o GH foi realizada a eutanásia dos animais. Os olhos foram submetidos à análise imuno-histoquímica com os anticorpos TNF-α e IL-6. Resultados: O GH manifestou significativo aumento do colesterol total e triglicerídeos em relação ao GN (p<0,001). Houve significativo aumento da expressão da TNF-α (p<0,001) e da IL-6 (p=0,002) na coroide e esclera dos animais do GH em relação ao GN. Conclusão: Este estudo demonstra que a dieta hipercolesterolêmica induz ao aumento da expressão das citocinas TNF-α e IL-6 na coroide e esclera de coelhos. .

Aumento da imunorreatividade ao VEGFR-1 no complexo coroido-escleral em modelo experimental de hipercolesterolemia / Increased VEGFR-1 immunoreactivity in the choroid-scleral complex in hypercholesterolemia experimental model

OBJETIVO: O objetivo deste trabalho é investigar a expressão do fator de crescimento vascular endotelial (VEGF) na coroide e esclera, utilizando um modelo experimental de hipercolesterolemia. MÉTODO: Coelhos New Zealand foram organizados em dois grupos: O grupo dieta normal (GN), composto por 8 coelhos (8 olhos), recebeu ração padrão para coelhos, durante 4 semanas; e o grupo hipercolesterolêmico (GH), composto por 13 coelhos (13 olhos), recebeu dieta rica em colesterol a 1% por 8 semanas. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 8ª semana para o GH e 4ª semana para o GN foi realizada a eutanásia dos animais e os olhos foram submetidos à análise imuno-histoquímica com os anticorpos RAM-11 e VEGFR-1. RESULTADOS: Observou-se significativo aumento do colesterol total e triglicerídeos do GH em relação ao GN (p<0,001). Houve significativo aumento da expressão da RAM-11 e VEGFR-1 na coroide e esclera dos animais do GH em relação ao GN (p<0,001). CONCLUSÃO: Este estudo demonstra que a dieta hipercolesterolêmica em coelhos induz ao aumento da concentração de macrófagos e da imunorreatividade ao VEGFR-1 na coroide e esclera, expressando similaridade com a degeneração macular relacionada à idade (DMRI) humana.

PURPOSE: The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF) in the choroid and sclera using hypercholesterolemia experimental model. METHODS: New Zealand rabbits were divided into two groups: 8 rabbits (8 eyes), in the normal diet group (NG), were fed by a standard diet for 4 weeks; and 13 rabbits (13 eyes), in the hypercholesterolemic group (HG), were fed by a 1% cholesterol-enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the initiation of the experiment and at the euthanasia time. After hypercholesterolemic group 8th week and NG 4th week, animals were euthanized and their eyes underwent immunohistochemical analysis with the RAM-11 and VEGFR-1). RESULTS: The diet has induced a significant increase in total cholesterol and triglyceride levels in HG when compared with NG (p<0.001). There was a significant increase in the RAM-11 and VEGFR-1 expressions in hypercholesterolemic group choroid and sclera in relation to NG (p<0,001). CONCLUSION: This study has revealed that the hypercholesterolemic diet in rabbits induces an increase in the macrophage concentration and immunoreactivity to VEGFR-1 in the choroid and sclera, resembling human age-related macular degeneration (ARMD).