Clinical Evidence of a Photoreceptor Origin in Diabetic Retinal Disease

Abstract

TopicAlthough diabetes is associated with a classic microvascular disease of the retina, it is also increasingly being recognized as a cause of retinal neuropathy. Preclinical evidence suggests that retinal neuropathy in diabetes manifests in part as photoreceptor dysfunction, preceding the development of vascular features in experimental models. Clinical SignificanceIt remains unknown whether such findings are relevant to patients with diabetes. MethodsHere we review four lines of clinical evidence suggesting that diabetes-associated photoreceptor pathology is linked to the development of retinal microvascular disease. ResultsFirst, a major population-based investigation of susceptibility loci for diabetic retinopathy implicated a photoreceptor protein product as a protective factor. Next, electroretinography and other studies of visual function collectively show that rod and/or cone-derived abnormalities occur decades before the development of vascular features of diabetic retinopathy. Third, protection from diabetic retinopathy seemingly develops in patients with co-incident retinitis pigmentosa, as suggested by several case series. Finally, based on anatomic features, we propose that the beneficial effect of macular laser in diabetic retinopathy occurs via ablation of diseased photoreceptors. ConclusionsThe evidence we present are limited due to the small patient populations used in the studies we cite and due to lack of methodologies that allow causative relationships to be inferred. Collectively, however, these clinical observations suggest that photoreceptors are involved in early diabetic retinal disease and may in fact give rise to the classic features of diabetic retinopathy.