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Ruilin Zhu, Kin-Sang Cho, Liu Yang, Dong Feng Chen; Ephrin-A2 and -A3 are negative regulators of photoreceptor regeneration in rhodopsin knockout mice.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3110.
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We showed previously that lack of ephrin-A3 enhances the proliferation and differentiation of retinal progenitor cells into photoreceptors in vitro. We hypothesize that absence of ephrin-A2/A3 promotes photoreceptor regeneration in rhodopsin knockout (Rho-/-) mice.
EdU was injected once daily for 7 consecutive days in 6 weeks old and 12 weeks old Rho-/-, and Rho-/-ephrin-A2-/-A3-/- (Rho-/-A2-/-A3-/-) mice, and proliferating cells were revealed by EdU immunolabeling in retinal sections. Photoreceptor morphology and function were examined in 6-week and 12-week old wild-type (WT), ephrin-A2-/-A3-/- (A2-/-A3-/-), Rho-/-, and Rho-/-ephrin-A2-/-A3-/- (Rho-/-A2-/-A3-/-) mice. The thickness of outer nuclear layer of the mouse retina was evaluated non-invasively by spectrum-domain optic coherence tomography (SD-OCT) and retinal function by electroretinograms (ERG).
In the ciliary body, neural retina, and RPE of Rho-/-A2-/-A3-/- mice, the numbers of proliferating cells were significantly higher than in Rho-/- mice. More proliferating cells in the Rho-/-A2-/-A3-/- mice were found to migrate to the outer nuclear layer (ONL) and differentiated into photoreceptors at 3 weeks post EdU administration. While A2-/-A3-/- mice exhibited normal retinal morphology as WT mice, both Rho-/- and Rho-/-A2-/-A3-/- mice showed significant degeneration of photoreceptor cells and thinning of the ONL. No significant improvement of retinal function as measured by ERG and ONL thickness was observed in Rho-/-A2-/-A3-/- mice compared to Rho-/- mice.
Our results suggest that absence of ephrin-A2/A3 promotes retinal cell proliferation in Rho-/-A2-/-A3-/- mice, although no significant improvement of ONL thickness and retinal ERG were noted in Rho-/-A2-/-A3-/- mice compared to Rho-/- mice.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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