Prostaglandin antagonist relieves blood-retinal barrier breakdown induced by anterior segment intraocular surgery in a rat model / O antagonista das prostaglandinas alivia a ruptura da barreira sanguínea retiniana induzida pela cirurgia intraocular do segmento anterior em um modelo em ratos

ABSTRACT Purpose: To evaluate the efficacy of prostaglandin antagonists on blood-retinal barrier breakdown induced by anterior segment intraocular simulated surgery. Methods: Rats were randomly assigned to a negative control group, model group, nonsteroidal anti-inflammatory drugs prophylactic treatment group, nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, and corticosteroid treatment group. Four hours and 48h after modeling, the concentrations of PGE1, PGE2, and PGF2 α in the aqueous humor and vitreous body of the rat model were visualized using ELISA. The integrity of the blood-retinal barrier was quantitatively measured using Evan's blue as a tracer. Results: Four hours after modeling, the concentrations of PGE1, PGE2, and PGF2α in the aqueous humor and vitreous body in the negative control group and the nonsteroidal anti-inflammatory drugs prophylactic treatment group were significantly lower than those in the model group. The concentrations of PGE1, PGE2, and PGF2α in the aqueous humor and vitreous body in the corticosteroid prophylactic treatment group were higher than those in the negative control group and the nonsteroidal anti-inflammatory drugs prophylactic treatment group. Forty-eight hours after modeling, the concentrations of PGE1, PGE2, and PGF2α in the aqueous humor and vitreous body in the nonsteroidal anti-inflammatory drugs prophylactic treatment group, nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, and corticosteroid treatment group were lower than those in the model group, but higher than those in the negative group. Retinal Evan's blue leakage in the nonsteroidal anti-inflammatory drugs prophylactic treatment group was higher than that in the negative control group, and lower than those in the nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, corticosteroid treatment group, and model group. Retinal Evan's blue leakage in the nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, and corticosteroid treatment group were lower than those in the model group. Conclusions: This study confirms that prostaglandin antagonists can relieve blood-retinal barrier breakdown in a rat model and that nonsteroidal anti-inflammatory drugs prophylactic treatment can achieve better efficacy.

RESUMO Objetivos: Avaliar a eficácia do antagonista de prostaglandinas no rompimento da barreira hemato-retiniana induzida por cirurgia simulada intraocular do segmento anterior. Métodos: Os ratos foram divididos aleatoriamente em grupo controle negativo, grupo modelo, grupo de tratamento profilático com drogas anti-inflamatórias não esteroides, grupo de tratamento com anti-inflamatórias não esteroides, grupo de tratamento profilático com corticosteroides e grupo de tratamento com corticosteroides. Quatro e 48h após a modelagem, as concentrações de PGE1, PGE2 e PGF2 α no humor aquoso e no corpo vítreo em modelo em ratos foram detectadas através de Elisa. A integridade da barreira hemato-retiniana foi quantitativamente mensurada utilizando o azul de Evans como marcador. Resultados: Quatro horas após a modelagem, as concentrações de PGE1, PGE2 e PGF2α no humor aquoso e no corpo vítreo no grupo controle negativo e no grupo de tratamento profilático com anti-inflamatórias não esteroides foram significativamente menores do que as do grupo modelo. As concentrações de PGE1, PGE2 e PGF2α no humor aquoso e no corpo vítreo no grupo de tratamento profilático com corticosteroides foram maiores do que as observadas no grupo controle negativo e no grupo de tratamento profilático com anti-inflamatórias não esteroides. 48h após a modelagem, as concentrações de PGE1, PGE2 e PGF2α no humor aquoso e no corpo vítreo no grupo de tratamento profilático com anti-inflamatórias não esteroides, no grupo de tratamento com anti-inflamatórias não esteroides, no grupo de tratamento profilático com corticosteroides e no grupo de tratamento com corticosteroides foram menores do que as observadas no grupo modelo e maiores que as observadas no grupo negativo. O extravasamento retinal de azul de Evans no grupo de tratamento profilático com anti-inflamatórias não esteroides foi maior que no grupo controle negativo e menor que nos grupos de tratamento com anti-inflamatórias não esteroides, de tratamento profilático com corticosteroides, de tratamento com corticosteroides e no grupo modelo. O extravasamento retinal de azul de Evans observado nos grupos de tratamento com anti-inflamatórias não esteroides, de tratamento profilático com corticosteroides e de tratamento com corticosteroides foi inferior ao observado no grupo modelo. Conclusões: Este estudo valida que o antagonista das prostaglandinas pode aliviar a ruptura da barreira hemato-retiniana em um modelo em ratos e que o tratamento profilático com anti-inflamatórias não esteroides pode alcançar melhor eficácia.

Chlorogenic Acid Decreases Retinal Vascular Hyperpermeability in Diabetic Rat Model

To evaluate the effect of chlorogenic acid (CGA), a polyphenol abundant in coffee, on retinal vascular leakage in the rat model of diabetic retinopathy, Sprague-Dawley rats were divided into four groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with 10 and 20 mg/kg chlorogenic acid intraperitoneally daily for 14 days, respectively. Blood-retinal barrier (BRB) breakdown was evaluated using FITC-dextran. Vascular endothelial growth factor (VEGF) distribution and expression level was evaluated with immunohistochemistry and Western blot analysis. Expression of tight junction proteins, occludin and claudin-5, and zonula occludens protein, ZO-1 was also evaluated with immunohistochemistry and Western blot analysis. BRB breakdown and increased vascular leakage was found in diabetic rats, with increased VEGF expression and down-regulation of occludin, claudin-5, and ZO-1. CGA treatment effectively preserved the expression of occludin, and decreased VEGF levels, leading to less BRB breakdown and less vascular leakage. CGA may have a preventive role in BRB breakdown in diabetic retinopathy by preserving tight junction protein levels and low VEGF levels.

Efeitos da latanoprosta sobre a espessura foveal em olhos submetidos à cirurgia de catarata / Influence of topical latanoprost on foveal thickness in eyes that underwent uneventful cataract surgery

OBJETIVO: Avaliar prospectivamente com o uso da tomografia de coerência óptica se o uso tópico de latanoprosta induz alterações retinianas em pacientes submetidos à cirurgia de catarata. MÉTODOS: Estudo clínico randomizado, com observador mascarado e um mês de duração. Pacientes pseudofácicos foram tratados com latanoprosta (n=10) ou lubrificante ocular uma vez ao dia (grupo controle - placebo) (n=10). Metade dos pacientes de cada grupo possuía capsulotomia posterior (Nd:YAG laser). Avaliamos o status da barreira hemato-retiniana pela medida da espessura retiniana na fóvea com a tomografia de coerência óptica. Exames de tomografia de coerência óptica e medida da acuidade visual foram realizados antes do início do estudo e com 15 e 30 dias de tratamento. RESULTADOS: Não foi observada alteração significante na média da espessura foveal do grupo controle (p>0,0610). Houve aumento significante na média da espessura foveal nos pacientes tratados com latanoprosta (p<0,0004). Não foi observada alteração na acuidade visual em nenhum paciente. A média da espessura retiniana na fóvea foi significativamente maior no grupo da latanoprosta (p<0,0007). A espessura foveal nos olhos tratados com latanoprosta com cápsula posterior rota foi significativamente maior que a dos pacientes com cápsula íntegra (p<0,0461). Comparando apenas os pacientes com cápsula posterior íntegra, houve diferença significante da espessura foveal entre os pacientes tratados com latanoprosta (236,4 ± 29,4 mm) e placebo (197,8 ± 19,3 mm) apenas na avaliação realizada com 30 dias de tratamento. CONCLUSÕES: Latanoprosta pode levar à quebra da barreira hemato-retiniana em pacientes pseudofácicos. Isso é mais provável de ocorrer em pacientes com cápsula posterior rota.

PURPOSE: To study prospectively using optical coherence tomography whether topical latanoprost induces retinal disorders in patients that underwent cataract surgery. METHODS: Randomized, masked-observer, one-month clinical trial. Pseudophakic patients were treated with latanoprost (n=10) or lubricant drop q.d. (control group) (n=10). Half of the patients of each group presented ruptured posterior capsule (Nd:YAG laser). We evaluated the blood-retinal barrier status assessed by optical coherence tomography measurement of retinal thickness in the fovea. Before the beginning of the study and after 15 and 30 days of treatment, optical coherence tomography images were taken, and the visual acuity examination was performed. RESULTS: There was no statistically significant increase in mean foveal thickness when patients instilled placebo (P>0.0610). A statistically significant increase in retinal thickness in the fovea was observed when patients instilled latanoprost (P<0.0004). No changes were observed in visual acuity in both groups. Mean retinal thickness in the fovea was significantly higher in the latanoprost group (P<0.0007). The mean foveal thickness in latanoprost treated eyes with ruptured posterior capsule was statistically greater when compared with that of intact posterior capsule (P<0.0461). When comparing only the patients with that of intact posterior capsule, there was a statistically significant difference in foveal thickness between patients treated with latanoprost (236.4 ± 29.4 mm) and placebo (197.8 ± 19.3 mm) only at 30 days of treatment. CONCLUSIONS: Latanoprost may lead to disruption of the blood-retinal barrier in pseudophakic patients, and is more probable to occur in patients with ruptured posterior capsule.

The Steroid Effect on the Blood-Ocular Barrier Change Induced by Triolein Emulsion as seen on Contrast-Enhanced MR Images

OBJECTIVE: The purpose of this study is to evaluate the effect of dexamethasone on the damaged blood-ocular barrier caused by triolein emulsion, using contrast-enhanced MR imaging. MATERIALS AND METHODS: An emulsion of 0.1-mL triolein in 20 mL of saline was infused into the carotid arteries of 32 cats, 12 cats were placed in the treatment group and 18 cats were placed in the Control group. Thirty minutes after the infusion of triolein emulsion, a set of orbital pre- and post-contrast T1-weighted MR images (T1WIs) were obtained. Infusion of 10 mg/kg dexamethasone into the ipsilateral carotid artery of each of the cats in the treatment group cats and 20 mL saline in each of the cats in the control group was given. A second set of pre- and post-contrast orbital T1WIs were obtained three hours following triolein emulsion infusion. Qualitative analysis was performed for the the anterior chamber (AC), the posterior chamber (PC), and in the vitreous humor of the ipsilateral and contralateral eyes. The signal intensity ratios of the ipsilateral eye over the contralateral eye were quantitatively evaluated in the three ocular chambers on the first and second set of T1WIs, and were then statistically compared. RESULTS: Qualitatively, the AC, the PC or the vitreous did not show immediate contrast enhancement on the first and the second set of post-contrast T1WIs. However, the AC and the PC showed delayed contrast enhancement for both groups of cats on the second pre-contrast T1WIs. No enhancement or minimally delayed enhancement was seen for the vitreous humor. Quantitatively, the signal intensity ratios in the PC of the treatment group of cats were statistically lower than the ratios of the control group of cats for the second set of T1WIs (p = 0.037). The AC and vitreous showed no statistically significant difference between the feline treatment group and control group (p > 0.05). CONCLUSION: Contrast-enhanced MR images revealed increased vascular permeability in the PC of the eye after infusion of triolein emulsion. Dexamethasone seems to decrease the breakdown of the blood-aqueous barrier in the PC.

The effect of subtenon injection of methylprednisolone acetate on the breakdown of blood retinal barrier after cryotherapy

Using computerized vitreous fluorophotometry (VFP, Fluorotron(TM)), we examined the effect of cryotherapy on the blood retinal barrier (BRB) and the effect of subtenon injection of methylprednisolone acetate (Depomedrol(R)). In experiment 1, the right eyes of the 13 pigmented rabbits were treated with heavy cryotherapy after baseline VFP readings. The freezes were applied at 6 places in each quadrant around the equator are in two rows, a total of 24 places circumferentially. The left eyes were reserved as controls. In 6 rabbits (cryo with steroid group), Depomedrol(R) 10 mg of Depomedrol was injected into subtenon space after cryotherapy. The other 7 rabbits were treated with cryotherapy only (cryo only group). The VFP readings were taken 1, 3, 5, and 7 days, 2, 3, 5, and 7 weeks after cryotherapy. Cryotherapy increased the breakdown of BRB significantly. The peak VFP readings were obtained 5 days after cryotherapy in the cryo only group and 7 days after cryotherapy in the cryo with steroid group. In the cryo only group, the severity of the breakdown of BRB was higher than in the cryo with steroid group, and the increased VFP readings could not be normalized until 7 weeks after cryotherapy. In experiment 2, both eyes of the 8 pigmented rabbits were treated with medium cryotherapy after baseline VFP readings. The freezes were applied at 3 places in the superior temporal quadrant and at 3 places in the superior nasal quadrant, a total of 6 places. Depomedrol(R) 10 mg was injected into subtenon space after cryotherapy in the right eyes only. The VFP readings were taken 1, 3, 5, 7, 10, and 14 days after cryotherapy. In this experiment, cryotherapy did not increase the breakdown of BRB. But in the right eye, the severity of the breakdown of BRB was significantly lower than in the left eye 7 and 10 days after cryotherapy. These results suggest that Depomedrol(R) can decrease the severity of the breakdown of BRB after cryotherapy, and may be useful in the prevention of proliferative vitreoretinopathy (PVR).