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V. V. Lyzogubov, R. G. Tytarenko, P. S. Bora, N. S. Bora; Relationship Between Complement Activation and Choroidal Neovascularization in Type II Diabetes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6182.
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© ARVO (1962-2015); The Authors (2016-present)
Choroidal vascular changes are tightly associated with the pathogenesis of diabetic retinopathy. Overall objective of the current proposal is to explore the relationship between wet AMD, diabetes and the complement system.
Choroidal neovascularization (CNV), a hallmark of wet AMD was induced in Zuker diabetic fatty (ZDF) rats (animal model of type II diabetes) and lean male rats (control) by Argon laser. The incidence as well as the size of CNV complex in Zucker and control rats was compared using flat mounted RPE-choroid-sclera, confocal microscopy and ImageJ program. Animals were sacrificed at day 10 post-laser to study the status of C3 split products and angiogenic growth factor - VEGF in RPE-choroid using semi-quantitative immunohistochemistry (IHC) and semi-quantitative Western blot analysis. Complement activation is necessary for the generation of C3 split products and cleavage of C3 protein is taken as a measure of complement activation in vivo within the eyes.
Our results demonstrate a statistically significant (P<0.05) increase in the size of neovascular complex in ZDF rats compared to controls. A combination of Western blot and IHC analysis revealed the presence of increased amount of C3 split products in the RPE and choroid of ZDF rats compared to controls. Additionally, increased expression of VEGF was detected in the RPE and choroid of ZDF rats compared to the controls by IHC and Western blotting.
Increased activation of complement system and increased expression of VEGF leads to severe choroidal neovascularization in type II diabetes.
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