Evaluation of vascular endothelial growth factor [VEGF] and B cell lymphocyte/ leukemia 2 [Bcl-2] protein levels in vitreous humor and serum of patients with proliferate diabetic retinopathy

ABSTRACT

Diabetic retinopathy [DR] is one of the most common microvascular complications of type 2 diabetes mellitus. In the proliferative stage of DR, neovascularization on the retina and the posterior surface of the vitreous occur. Vascular endothelial growth factor [VEGF] is considered to be the most potent factor for retinal neovascularization. Several hypotheses were thought to be involved in the endothelial cell survival activity of VEGF; among them is its ability to induce antiapoptotic proteins like B-cell Lymphocyte/ Leukemia 2 [Bcl-2]. Aim of the study was evaluating the levels of VEGF and Bcl-2 protein in the vitreous humor and sera of patients with proliferative diabetic retinopathy [PDR]. The patients group included twenty five type 2 diabetic patients with proliferative retinopathy and subjected to vitrectomy, and fifteen non-diabetic individuals subjected to vitrectomy for various non proliferative ocular diseases were taken as a control group. All the participants were subjected to a thorough physical examination and full ophthalmologic evaluation. Laboratory investigations included measurement of serum levels and activities of glucose, urea, creatinine, total cholesterol and its fractions, triglycerides, alanine and aspartate aminotransferases [ALT and AST], as well as the percentage of whole blood glycated hemoglobin [HbA[1c]. The VEGF and Bcl-2 were measured in the vitreous humor and sera of all studied subjects using enzyme immunoassays. The VEGF and Bcl-2 levels were found to be significantly increased in the vitreous humor of patients with proliferative DR when compared to their corresponding control group [p=0.001 andp-0.003 respectively]. On the other hand, no statistically significant difference was noted between both groups regarding serum values of both VEGF and Bcl-2 [p> 0.05]. Furthermore, a significant positive correlation was found between serum Bcl-2 and serum VEGF in the patients group [r= 0.463, p= 0.020]. The significantly higher values of VEGF and Bcl-2 in the vitreous humor of patients with PDR, with the lack of such findings in their sera, suggest that both factors are implicated in the pathogenesis of this disease, and support the hypothesis that their increased levels in the vitreous is attributed to intraocular synthesis, in response to retinal hypoxia and ischemia, rather than to serum filtration. Furthermore, the significant correlation between both VEGF and Bcl-2 in serum of PDR patients could be related to the VEGF ability to induce pathological angiogenesis in PDR through the up regulation of the anti apoptotic protein Bcl-2 that promotes new vessels survival rendering their vitreous levels high which would probably be reflected on their serum levels as neovascularization is the main pathology in the PDR