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Sandrine Joly, Vincent Pernet, Anna Guzik-Kornacka, Martin E Schwab; Vulnerability of direction-selective ganglion cells and starburst amacrine cells to ischemia-reperfusion in the adult mouse retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1896.
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© ARVO (1962-2015); The Authors (2016-present)
Central vein and artery occlusion (CVAO) have devastating effects on the inner retinal cells composed of retinal ganglion cells (RGCs) and amacrine cells. In this study, we aimed at investigating the degeneration time course of direction-selective ganglion cells (DSGCs) and starburst amacrine cells (SACs) required for object motion detection in a mouse model of CVAO.
To block the inner retinal circulation, the optic nerve sheath containing the central vein and artery was ligated with a 9.0 suture in the orbit of C57BL/6 adult mice without damaging the optic nerve. After 60 min, reperfusion was allowed by removing the suture. Functional deficits were weekly monitored by measuring the optokinetic response of each eye separately. At 10 and 21 days after ischemia-reperfusion, the survival of the whole population of RGCs, of ON-OFF direction-selective RGCs, of ON and OFF SACs was assessed on retinal flat-mounts by immunohistochemistry using β3Tubulin, cocaine and amphetamine regulated transcript (CART) and Choline AcetylTransferase (ChAT) respectively as specific markers..
As early as 7 days after ischemia-reperfusion, the optokinetic response was completely abolished while ~35 % and ~22% of RGCs stayed alive 10 and 21 days post injury respectively. By immunohistochemistry, the density of CART-positive RGCs decreased to 18% and 12% compared with intact retinae 10 and 21 days after reperfusion. The striking reduction in CART detection could be due to CART protein down-regulation in DSGCs or to cell death. In the ganglion cell layer (GCL), only 34% and 24% of ON SACs remained in the retina at the two time points whereas in the inner nuclear layer (INL) OFF SACs dropped to 78% and 54% of the control retina values. The percentage of surviving cells suggest a faster and more massive loss of RGCs and ON SACs in the GCL than of OFF SACs in the INL. In contrast, the elimination of RGCs triggered by optic nerve crush did not affect the number of ON and OFF SACS, indicating that SACs degeneration may not be attributable to RGC cell death after ischemia-reperfusion.
RGCs and ON SACs are more vulnerable than OFF SACs to ischemic insults caused by CVAO in mice. Future experiments will be carried out to understand if remaining SACs and DSGCs can be stimulated to restore the visual function measurable with the optokinetic test.
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