Journal of Clinical and Experimental Ophthalmology
Open Access
ISSN: 2155-9570
+44 1223 790975
ISSN: 2155-9570
+44 1223 790975
Rashidul Haque
Emory University School of Medicine, USA
Keynote: J Clin Exp Ophthalmol
Angiotensin (Ang) II, the most physiologically active component of RAS, mediates its effect through two G-protein coupled receptors, Ang II type-1 or type-2 (AT1R and AT2R), having different signal transduction mechanisms. Most of the known cardiovascular effects of Ang II are mediated by AT1R. Pro-renin has long been considered as an inactive precursor of renin, without any biological function of its own. However, pro-renin binding to a receptor called (pro)renin receptor (PRR) has been recently reported to exert biological effects in the retina. It is also known now that pro-renin is highly elevated in ocular fluid of diabetic patients with proliferative retinopathy, which all suggest that pro-renin and the system RAS are very important in the eye. Using RNA interference tools, we have shown that both the receptors are implicated in hyperglycemia-induced increase of vascular endothelial growth factor (VEGF), VEGFR2 and transforming growth factor beta (TGF�?²1). In order to block the effect of Ang II through AT1R and AT2R, in our experiments we inhibited angiotensin converting enzyme (ACE) by perindopril, where Ang II formation is blocked. We have shown that the increased pro-renin synthesis due to hyperglycemia has been attributed to the activation of PRR and VEGF by a mechanism involving NADPH oxidase activity, miRNA-21, HIF1-�?± and NF-�?ºB. Furthermore, we have demonstrated that the downstream targets of miR-21 are three important genes SMAD7, an inhibitor of TGF-�?²1-induced VEGF expression, PTEN, a negative regulator of PI3 kinase/Akt signaling pathway and SPRY1, a negative regulator of ERK signaling pathway. The PRR-mediated induction of VEGF under hyperglycemic conditions occurs via Rac1 signaling by regulating miR-21 expression. Our studies suggest that hyperglycemia-induced PRR signaling may play a role in the VEGF-induced angiogenesis that may lead to proliferative diabetic retinopathy, wet AMD and other vascular complications in the eye.
Rashidul Haque has been involved in several research projects including the role of circadian clocks in the retinal function and the potential role of microRNA in the regulation of renin angiotensin system in the retina. He has characterized a couple of microRNA molecules and investigated their role in diabetic retinopathy and other ocular diseases.