PERSPECTIVES IN THE TREATMENT OF DIABETIC-RETINOPATHY

With regard to diabetic retinopathy, in addition to the demonstration by the DCCT study that prevention is achieved by good metabolic contro l, our present knowledge on physiopathology leads us to imagine three types of possible therapeutic approach; inhibition of glucotoxicity, i mprovement of capillary flow, blockade of angiogenesis. 1) Inhibition of glucotoxicity Aldose reductase inhibitors can prevent cataract in d iabetic or galactosemic rats. The effect of these drugs on retinopathy , evaluated in some clinical trials, remains controversed, suggesting a minor role. Aminoguanidine is an inhibitor of formation of advanced glycosylation end-products (AGE). This compound has been tested on a m odel of experimental retinopathy in rats. Parellely to the AGE decreas e in retina, formation of microanevrysms and loss of endothelial cells in capillars were delayed. Clinical tolerance allows human applicatio n and randomised trials will give further information on this potentia lly efficient drug. 2) Improvement of capillary flow This objective ca n be obtained by drugs inhibiting platelet agregation or improving ery throcyte or leucocyte deformability. Clinical trials using such compou nds were not very conclusive. 3) Blockade of angiogenesis Proliferatio n of new vessels is a rather severe stage of diabetic retinopathy. Ang iogenesis is due to factors locally produced (as FGF, TGF and uPA prod uced by anoxic tissues), systemic (IGF1) or released by inflammatory r eaction (IL1, TNF alpha and beta). One imagines usage of drugs which i nhibit these factors and prevent angiogenesis. At the present time, tw o approaches have been used in proliferative retinopathy worsening des pite panphotocoagulation; analogues of somatostatine and interferon al pha. The promessing results of these pilot studies have to be confirme d. For the future, other angiostatic compounds could be used as hepari n-steroide conjugates. Indeed it seems that this approach which could benefit of researches in carcinology, should lead to new therapeutic a gents very soon.