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Madhu Nath, Rajvardhan Azad, Ashok kumar Deorari, Baskar Singh, Neelima Aron, Thirumurthy Velpandian; INVOLVEMENT OF RETINAL RENIN ANGIOTENSIN PATHWAY IN EXPERIMENTAL MODEL OF RETINOPATHY OF PREMATURITY. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1901.
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Renin angiotensin system is well established in ocular tissues, alteration in this system during developing stage of retinal vessel in prematurely born neonate can lead to ROP, which is the leading cause of blindness and visual morbidity in the surviving premature infants.Modulation of RAS pathway through pharmacological intervention can be proved as effective therapy for this neonatal blinding disease in near future.
Wistar rat pups were exposed to high oxygen saturation (75%) in a controlled chamber, from 7th -12th postnatal day. On day 12th pups were randomised in to receive ACE inhibitor (lisinopril 0.07mg/kg), AT1 receptor blocker (telmisartan 7mg/kg)) and both in combination. Bevacizumab was used as a positive control and saline treated pups served as untreated control. Drugs and saline were injected through subcutaneous route in two divided doses in 48 hours interval. Structural and functional health of retina were assessed by tortuosity index of blood vessels and electroretinography respectively on PD 17 and 25 using MICRON III rodent imaging system. ROP rats were compared with normoxia rat pups. Rat pups were sacrificed and retina were extracted to study the gene expression of RAS components in various test groups.
Retinopathy was assessed in the terms of tortuosity of vessels from optic nerve head to posterior pole of retina. It is been observed that arterioles were more effected than venules. There was a significant increase in arteriole tortuosity in sham with comparison to normoxia group (p=0.002). When compared with sham, bevacizumab (p=0.040), lisinopril (p=0.003), telmisartan (p=0.002) and Lisinopril plus Telmisartan combination (p=0.002) group has shown significant decrease in tortuosity and were comparable to normoxia group. In ERG responses, on Day 17 there was a 66% reduction in the b wave amplitude in Sham as compared to Room air (p=0.002). The b wave amplitude of the drug treatment groups were comparable to room air. Expression of RAS components of various groups were also altered.
Retinopathy was hindered in various groups viz. Lisinopril, Telmisartan and their combination, respectively as evidenced by improved ‘b’ wave and lesser tortuosity index. Further studies are in process to evaluate its the clinical utility with the help of intravitreal delivery system.
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