Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice.

Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and a useful platform for developing new therapies.

[Choroidal vessels alterations in treated and untreated diabetic rats]. / Alterações vasculares na coróide de ratos diabéticos tratados e não tratados.

PURPOSE: To evaluate the diabetic alterations and the impact of short and long-term medical treatment on them. METHODS: Thirty Wistar rats were divided into 3 groups: control (GC), diabetic (DG), and treated diabetic (TG) and the observations were made 1 month (M1) and 12 months (M2) after diabetes induction. Diabetes was induced by intravenous alloxan (42 mg/kg). The treated group received acarbose orally and insulin by subcutaneous injection. Eyes were prepared for transmission electron microscopy, specifically for ultrastructure of the Bruch membrane and choroidal vessels. RESULTS: Ultrastructural examination of the diabetic rat choroid showed deposits in the Bruch membrane and accumulation of vesicles, glycogen and dense bodies in endothelial cell cytoplasm. The most affected group was that of the diabetics on month 12 (GDM2). The treated diabetics showed the least alterations on month 12 (GTM2). CONCLUSION: Diabetic rats develop degenerative alterations in the Bruch membrane and choroidal vessels. These alterations are more evident in animals submitted to chronic disease, but they are also present in acute disease. Degenerative processes were not avoided with short-term treatment. Long-term treatment inhibited the progress of these processes.

Alterações vasculares na coróide de ratos diabéticos tratados e não tratados / Choroidal vessels alterations in treated and untreated diabetic rats

OBJETIVO: Conhecer os efeitos do diabetes e o impacto de seu tratamento medicamentoso em curto e longo prazo sobre os vasos da coróide e membrana de Bruch. MÉTODOS: Foram estudados 30 ratos Wistar, divididos em 3 grupos experimentais: grupo controle (GC), grupo diabético (GD) e grupo diabético tratado (GT), estudados 1 mês (momento M1) e 12 meses (momento M2) após o início do experimento. O diabetes foi induzido por aloxana endovenosa, na dose de 42 mg/kg. O GT foi tratado com hipoglicemiante oral (acarbose) e insulina subcutânea. Após o sacrifício, os olhos foram preparados para exame ao microscópio eletrônico de transmissão, interessando a ultra-estrutura da membrana de Bruch e os vasos da coróide. RESULTADOS: O exame ultra-estrutural da coróide dos ratos diabéticos mostrou depósitos na membrana de Bruch, acúmulo de vesículas, glicogênio e corpos densos no citoplasma das células endoteliais. O grupo mais afetado foi de ratos diabéticos de 12 meses (GDM2). Os animais com menor intensidade de alterações foram os ratos tratados por 12 meses (GTM2). CONCLUSÃO: Os ratos diabéticos desenvolveram alterações degenerativas na membrana de Bruch e vasos da coróide. Estas alterações foram mais evidentes nos animais submetidos à doença crônica, mas também ocorreram agudamente. O tratamento a curto prazo não foi capaz de evitar os processos degenerativos. A longo prazo, o tratamento inibiu a progressão destes processos.

PURPOSE: To evaluate the diabetic alterations and the impact of short and long-term medical treatment on them. METHODS: Thirty Wistar rats were divided into 3 groups: control (GC), diabetic (DG), and treated diabetic (TG) and the observations were made 1 month (M1) and 12 months (M2) after diabetes induction. Diabetes was induced by intravenous alloxan (42 mg/kg). The treated group received acarbose orally and insulin by subcutaneous injection. Eyes were prepared for transmission electron microscopy, specifically for ultrastructure of the Bruch membrane and choroidal vessels. RESULTS: Ultrastructural examination of the diabetic rat coroid showed deposits in the Bruch membrane and accumulation of vesicles, glycogen and dense bodies in endothelial cell cytoplasm. The most affected group was that of the diabetics on month 12 (GDM2). The treated diabetics showed the least alterations on month 12 (GTM2). CONCLUSION: Diabetic rats develop degenerative alterations in the Bruch membrane and choroidal vessels. These alterations are more evident in animals submitted to chronic disease, but they are also present in acute disease. Degenerative processes were not avoided with short-term treatment. Long-term treatment inhibited the progress of these processes.