Diabetic retinopathy ‐ Apoptosis and BRB breakdown prevention in early diabetic retinopathy

Abstract Purpose Diabetic retinopathy (DR) is complex multifactorial neurovascular degenerative complication of systemic disease with evidence of inflammation/oxidative stress induced by hyperglycemia leading to early retinal cell apoptosis and BRB breakdown confirmed in STZ diabetic rats. Erythropoietin (EPO,40.3kDa) multifuctional protein approved drug for anemia has confirmed antiapoptotic effects in retinal cell cultures, various models of stress: ischaemia, reperfusion,glaucoma,diabetes: rats, mice, rabbits. It is upregulated in the retina in prolipherative DR. We studied EPO serum levels in diabetics with and without retinopathy comparing to non diabetic controls. Methods In 60 type 2 diabetics, 26 with and 34 without retinopathy of both sexes and age of 64.24 ± 11.64 years EPO serum was determined (mIu/ml) by ELISA and compared to 44 non diabetics, age and sex matched controls. Student t test was used. Results EPO serum levels were high in retinopathy patients 15±11.14 vs 9.47±6.57 in controls p=0.043. Intermediary levels in diabetics without retinopathy 10.84±6.11. Conclusion High EPO serum expression in diabetic retinopathy supports endogenous overproduction by Hif‐1?, as protective mechanism of BRB breakdown and vascular/neuronal cell apoptosis demonstrated in STZ diabetic rats. Intravitreal EPO prevented all early diabetic retinal changes by activation of Erk 1/2 pathway. Antioxidant/inflamatory related molecules earlier studied, TMR, Haptoglobin, ACP, MHR and EpOx give additional support to this hypothesis. These proteins are related to EPO and ACE activity. EPO besides retinopathy preventive is angiogenic with viscosity effects. EPO derivative carbamylated forms which do not raise hematocrit have been developed.