Translational research in retinal vascular disease. An approach.

The clinical presentation of the most frequent vision threatening retinal diseases is dominated by lesions indicating that disturbances in retinal blood flow are involved in the pathogenesis of these diseases. The present review describes the experience from a translational strategy pursued to investigate retinal vascular diseases with diabetic retinopathy as the main object. The normal regulation of retinal blood flow is investigated in porcine retinal vessels in vitro and ex vivo. Subsequently, the in vitro findings are translated to clinical studies in normal persons in vivo, and it is investigated whether the mechanisms are disturbed in retinal vascular disease. This is followed by clinical intervention studies on these diseases. The approach has been used to investigate pressure autoregulation, metabolic autoregulation and vasomotion in retinal vessels. The investigations have shown that retinal vascular tone can be regulated by receptor-specific agonists and antagonists to vasoactive compounds such as purines, prostaglandins and nitric oxide synthesis and that the vasoactive effects can be modulated by the concentration and the mode of administration of these compounds. Additionally, it has been shown that retinal precapillary arterioles and capillaries not visible by ophthalmoscopy may play an important role for the pathophysiology of retinal vascular disease and its treatment. Future studies should focus on investigating normal and pathological regulation of retinal blood flow in these smaller vessels.