Downregulation of fibronectin overexpression reduces basement membrane thickening and vascular lesions in retinas of galactose-fed rats. Diabetes

Overexpression of extracellular matrix (ECM) compo-nents is closely associated with the development of vascular basement membrane (BM) thickening, a histo-logical hallmark of diabetic microangiopathy. To deter-mine whether BM thickening of retinal capillaries could be prevented by down regulating synthesis of fibronec-tin, an ECM component, we used antisense oligos tar-geted against translation initiation site of the fibronectin transcript in galactose-fed rat, an animal model of diabetic retinopathy. After 2 months of galac-tose-feeding, intravitreal administration of 3 mol/l antisense fibronectin oligos was initiated at monthly intervals for 3 months. The antisense strategy signifi-cantly reduced fibronectin mRNA and protein level in the retinas of treated eyes compared with untreate