The role of the extracellular matrix in retinal vascular disease

Originally believed to serve as a selective barrier and scaffold to which cells adhere, it has become evident that the individual components of the basement membrane (BM) are regulators of biological activities such as cell growth, differentiation, and migration, and that they influence tissue development and repair (Erickson and Couchman, 2000). Based on the emerging importance ofBM's in critical aspects of cellular activity, this thesis was undertaken in an attempt to further elucidate the role of these biologically-active regulatory proteins in the context of.retinal microvascular disease. The salient findings of this investigation were as follows; The a2(IV)NCl domain of typ~ IV human collagen inhibits angiogenesis in the retinal microvasculature in both in vitro (p<O.OOl) and in vivo (p<O.OOl) models .of pre-retinal neovascularisation thus emerging as a potential drug candidate for the treatment of proliferative retinopathies. Culture of primary bovine retinal microvascular endothelial cells (RMEC) upon Advanced Glycation End-Product (AGE) modified fibronectin significantly decreases cell attachment (p<O.OOl) and spreading (p<O.OO 1) capacity with a concomitant increase in cellular apoptosis (p<0.05) in comparison to RMEC cultured on native fibronectin. These fmdings are associated with decreased cell survival signalling as elicited through the FAKIAkt pathway. Surviving RMEC demonstrate an increase in cellular proliferation (p<O.05), superoxide production (p<O.05), and various basement membrane constituent mRNA expression (p