Angiotensin Receptor Blockade in Retinopathy of Prematurity: An Experimental Study

Abstract

PurposeRetinal renin angiotensin (RRAS) system has been reported to play a vital role in the retinal angiogenesis pathway. Present study was conducted to evaluate the modulation of RRAS components by quantitative gene expression studies in retina and to evaluate the effect of angiotensin receptor1 (AT1) blockade in the oxygen induced retinopathy (OIR) experimental model.MethodsNeonatal Wistar rat pups were exposed to high oxygen saturation (75% ±2%) chamber, from postnatal day (PD) 7th to postnatal day 12th. On PD 12th the pups were randomised into four groups (n = 9) viz. disease control (saline treated), AT1 receptor blocker (ARB) treated (telmisartan), antibody against VEGF (AAV) treated positive control (bevacizumab) and pups grew up in normoxia. On Day 17th Rat pup retina was assessed through fundus imaging and electroretinogram (ERG) by MICRON III. Rat pups were then sacrificed and retinas were extracted to study the gene expression of RAS components (renin, angiotensinogen, AT1 receptor & ACE), VEGF and HIF 1α in various test groups. Flat mounted ADPase stained retinas were subjected for light microscopy. Rat pups plasma, vitreous and retina were subjected for LC‐MS/MS.ResultsExamination of rat pup retina through fundus imaging, ADPase staining and ERG showed the reduction in tortousity index,vessel density of the retinal vasculature and improved “b” wave. Gene expression analysis revealed that treatment with ARB was able to normalise the expression of all the genes to a significant level except renin levels. ARB concentration in the retina was found to be therapeutically effective.ConclusionsPresent study shows Intervening in the over activated RRA system through angiotensin receptor 1 blockade was able to regulate this system in experimental model of ROP. Further studies are in progress to understand the RRAS mechanisms involved in ROP.