Biologia Molecular: Acesso Aberto

Evaluation of Antiangiogenic Potential of MMP₂ Antisense Oligonucleotide for the Management of Proliferative Diabetic Retinopathy Using Chicken Chorioallantoic Membrane

Abstract

Reji Manjunathan and Malathi Ragunathan

Proliferative diabetic retinopathy (PDR) is the advanced stage of diabetic retinopathy in which neovascularization occurs at the retina. Angiogenesis, the formation of new vessels from the existing one involves sequential step starting from the degradation of basement membrane by matrix metalloproteinases (MMPs). The elevated expression of MMP2 is considered as the one of the important parameter in the progress of PDR. Therefore, it is important to inhibit the activity of MMP2 in the retina of the PDR patients for the management of the diseases. In this concern we examined the anti angiogenic potential of antisense MMP2 oligonucleotide using chicken late CAM (chorio allantoic membrane) using various techniques. CAM has been used as a model for retinal research by ophthalmologist for many years due to its similarities with retina in the tissue thickness and blood vessels formation. MMP2 ASO inhibited blood vessels growth at the treated area and their length and size and reduced the thickness of the CAM compared to control. MMP2 ASO enhanced the accumulation of fibroblast and flattened endothelial cells and reduced the expression of MMP2 at gene and protein level. The chorionic epithelial layer of the CAM got flattened after the treatment with MMP2 ASO as an indication of lack of blood vessels formation and growth at the treated area. Altogether, our results demonstrates that MMP2 ASO is able to inhibit neovascularization effectively and therefore can be a suitable therapeutic molecule in the management of pathological neovascularization.