Possible involvement of endothelin-1 and nitric oxide in the pathogenesis of proliferative diabetic retinopathy

Background: Overproduction of endothelin-1 (ET-1) and nitric oxide (NO) in the retina is demonstrated in experimental diabetic animals. To clarify the possible involvement of ET-1 and NO in the pathogenesis of diabetic retinopathy, the authors examined the vitreous levels of these principal endothelium-derived vasoactive substances in patients with proliferative diabetic retinopathy (PDR). Methods: Vitreous fluid was taken from patients with PDR (ET-1, n = 12; NO, n = 12) and from patients with macular holes as controls (ET-1, n = 10; NO, n = 10) at vitreous surgery. Endothelin-1 and NO metabolites were measured by radioimmunoassay and high-performance liquid chromatography based on the Griess method, respectively. Results: Endothelin-1 levels (mean +/- SE) were 21.5 +/- 1.7 pg/mL in the vitreous of patients with PDR and 16.7 +/- 0.7 pg/mL in the vitreous of patients with macular hole. There was a significant difference between patients with PDR and controls (P = 0.009, Mann-Whitney). Nitrate (NO3) was 49.8 +/- 5.0 mumol/L in patients with PDR and 24.2 +/- 2.8 mumol/L in patients with macula hole; it was also significantly elevated in patients with PDR (P = 0.004, Mann-Whitney), whereas nitrite (NO2) was not detected in this study. Conclusion: These results indicate that ET-1 and NO may be related in the pathogenesis of PDR.