Immunolocalisation of the VEGF receptors FLT-1, KDR, and FLT-4 in diabeticretinopathy

Aim-To determine the spatial and temporal changes in the staining pattern o f the VEGF receptors FLT-1, KDR, and the putative receptor FLT-4 during the pathogenesis of diabetic retinopathy. Methods-Immunohistochemical localisation of VEGF receptors, using antibodie s against FLT-1, FLT-4, and KDR, was carried out on specimens of normal hum an retina (n=10), diabetic retinas (a) with no overt retinopathy (n=12), (b ) with intraretinal vascular abnormalities but no proliferative retinopathy (n=5), (c) with active proliferative retinopathy (n=6), and (d) with no re sidual proliferative retinopathy after scatter photocoagulation therapy (n= 14), and surgically excised diabetic fibrovascular membranes (n=11). The de gree and pattern of immunostaining was recorded. Results-FLT-1 staining was apparent in the retinas from both non-diabetic a nd diabetic retinas; weak to moderate staining was generally confined to th e inner nuclear layer, the ganglion cell layer, and the retinal vessels dur ing all stages of the disease process. Staining of the retinal vessels was raised in diabetic tissue compared with non-diabetic tissue. The preretinal vessels of the diabetic subjects stained moderately to intensely for FLT-1 . In contrast with FLT-1 staining minimal immunostaining for KDR was demons trated in the non-diabetic eyes and the unlasered eyes; however, weak stain ing for KDR was observed in the inner nuclear layer and the ganglion cell l ayer of the unlasered eyes with diabetic changes. In those retinas with pre retinal neovascularisation KDR immunoreactivity was moderate to intense in the intra- and preretinal vessels. However, in the excised membranes, where the vessels may have been in a quiescent state, the levels of KDR were wea k to moderate. After apparently successful laser treatment KDR staining was reduced in the intraretinal vessels. Minimal FLT-4 staining was observed t hroughout normal eyes while weak to moderate FLT-4 staining was generally c onfined to the inner nuclear layer and the ganglion cell layer of the unlas ered diabetic eyes. Weak to moderate levels of FLT-4 staining were observed in the intraretinal vessels except after apparently successful laser treat ment where reduced levels of staining were observed. Weak to moderate stain ing was observed in the preretinal vessels. Conclusions-This study supports a role for FLT-1, KDR, and possibly FLT-4 i n the pathogenesis of diabetic retinopathy; however, their specific roles i n the progression of the disease may differ.