Changes in the density and localisation of endothelin receptors in the early stages of rat diabetic retinopathy and the effect of insulin treatment

Aims/hypothesis. The endothelin system (ET system) has been implicated in t he retinal blood flow abnormalities that precede the onset of diabetic reti nopathy. This study was undertaken to assess whether the density and locali sation of both the immunoreactive endothelin-1 and endothelin receptors in rat retina change in the early stages of diabetes and the insulin treatment would affect those changes. Methods. Untreated streptozotocin-diabetic, insulin-treated streptozotocin- diabetic and age-matched control rats were killed 15, 45 and 90 days after the induction of diabetes. Binding assays were used to determine the densit y and proportion of endothelin receptors in neural retinal membranes. Local isation of endothelin receptors and immunoreactive endothelin-1 were analys ed by microautoradiography and immunohistochemistry, respectively. Results. Fifteen days after the induction of diabetes, the neural retinal m embranes of untreated streptozotocin-diabetic rats showed a statistically s ignificant decrease in the density of both endothelin receptor subtypes whe n compared with age-matched control rats. At 90 days, however, the density of endothelin receptors type B was statistically significantly higher than that of control rats, and the innermost layers of the diabetic retina also showed an increase of both endothelin receptor type B receptor and immunore active endothelin-1 signal. Insulin treatment during 90 days up-regulated e ndothelin receptor type A in neural retinal membranes and in the innermost layers of the retina when compared with control retinas. Conclusion/interpretation. These results show that the endothelin system is altered in both vascular and neuronal components of the retina in early di abetic retinopathy. The up-regulation of endothelin receptor type A induced by insulin treatment suggests that insulin might be involved in retinal mi croangiopathy.