Purchase this article with an account.
E. L. Fletcher, L. Downie, K. Hatzopoulos, K. Vessey, M. Pianta, A. Vingrys, J. Wilkinson-Berka, M. Kalloniatis; Angiotensin Type-1 Receptor Inhibition Is Neuroprotective to Amacrine Cells in a Rat Model of Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3119.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Retinopathy of Prematurity (ROP) is a retinal vascular disease associated with deficits in the scotopic vision. The aim of this study was to characterize in detail the neuronal deficits that occur in a rat model of ROP, and whether the angiotensin II type-1 receptor (AT1R) inhibitor, valsartan, alters retinal neurochemistry and cell survival.
Newborn Sprague-Dawley rats were exposed either to 80%:21% O2 (22:2 hours/day) until postnatal day 11 (P11), then 7 days room air, or room air for the entire experimental period. Valsartan (40 mg/kg/day) was administered from P12-P18. Retinae were aldehyde fixed and either resin embedded, sectioned at 180nm and processed for serial section post-embedding IMCC (primary antisera: glutamate, GABA, glycine, aspartate, glutamine, taurine; kindly donated by Prof RE Marc), or sectioned at 12µM on a cryostat. Cell death was assessed by quantification of TUNEL positive cells. Amacrine cell changes were detected by analysis using antisera directed against tyrosine hydroxylase (TH), protein kinase C (PKC), parvalbumin (PV), and angiotensin receptor 2 (AT2R)
Amino acid immunocytochemistry revealed widespread changes in virtually all classes of neurons, and especially amacrine cells. Pattern recognition analysis showed a reduction in amacrine cell classes including one that includes AII amacrine cells, the main interneurons of the rod pathway. There was a decrease in the density of amacrine cells in retinae with ROP; glycine and not GABA immunoreactive amacrine cells density was reduced. Neuronal loss was confirmed by a reduction in thickness of the INL and IPL and a significant increase in TUNEL labelling from P11-P13. Further evaluation of the change in amacrine cells during ROP revealed a significant reduction in PV-immunoreactive, AII amacrine cell density. There were no changes in the density of other amacrine cell types including TH, PKC , or AT2R amacrine cells. Treatment with valsartan, prevented the loss of AII amacrine cells and partially ameliorated neurochemical changes.
This study shows that neurons within inner retina especially AII amacrine cells are particularly affected by ROP, and that treatment with an AT1 receptor antagonist, is partially protective. The effect on AII amacrine cells could explain the deficits in scotopic vision previously reported.
This PDF is available to Subscribers Only