June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Absence of ephrin-A2/A3 promotes photoreceptor regeneration in rhodopsin knockout mice
Author Affiliations & Notes
  • Ruilin Zhu
    Department of Ophthalmology, Peking University First Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China
    Schepens Eye Research Institue, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA
  • Kin-Sang Cho
    Schepens Eye Research Institue, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA
  • Yuan Fang
    Shanghai Eye and ENT hospital, Shanghai, China
  • Christine Xu
    Schepens Eye Research Institue, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA
  • Liu Yang
    Department of Ophthalmology, Peking University First Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China
  • Dong Chen
    Schepens Eye Research Institue, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA
    Boston VA Healthcare System, Boston, MA
  • Footnotes
    Commercial Relationships Ruilin Zhu, None; Kin-Sang Cho, None; Yuan Fang, None; Christine Xu, None; Liu Yang, None; Dong Chen, GlaxoSmithKline (F), Patent/Schepens Eye Research Institute (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1166. doi:
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    • Get Citation

      Ruilin Zhu, Kin-Sang Cho, Yuan Fang, Christine Xu, Liu Yang, Dong Chen; Absence of ephrin-A2/A3 promotes photoreceptor regeneration in rhodopsin knockout mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1166.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: We showed previously that ephrin-A2/A3 are negative regulators of neural progenitor cell proliferation in the mature central nervous system, including retina. 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 and rescue vision loss in rhodopsin knockout (rho-/-) mice.

Methods: Photoreceptor morphology and function were examined in wild-type (WT), ephrin-A2-/-A3-/- (A2-/-A3-/-), rho-/-, and rho-/-ephrin-A2-/-A3-/- (rho-/-A2-/-A3-/-) mice. Proliferating retinal progenitor cells in the retina were labeled by injecting BrdU (50mg/kg; i.p.) twice daily for 7 days and revealed by immunolabeling with anti-BrdU in retinal sections. Photoreceptor cell loss and regeneration were assessed by counting recoverin+ (rods) or cone-arrestin+ (cones) photoreceptors and BrdU+ photoreceptor rods and cones. Moreover, retinal morphology and function were evaluated non-invasively in live mice by spectrum-domain optic coherence tomography and electroretinograms.

Results: 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 outer nuclear layer (ONL). BrdU+ cells were observed in retinal sections of A2-/-A3-/- and rho-/-A2/-A3- mice, but not in those of WT and rho-/- mice. BrdU+recoverin+ cells were observed in the ONL of rho-/-A2-/-A3- mice but not the other tested strains.

Conclusions: Our results suggest that ephrin-A2 and -A3 are key inhibitors for the regenerative potential of retinal progenitor cells and absence of ephrin-A2/A3 promote the proliferation and differentiation of retinal progenitor cells into photoreceptor. Thus, suppression of ephrin-A2/A3 signaling may represent a novel approach of cells-based therapy for photoreceptor degeneration disease.

Keywords: 648 photoreceptors • 696 retinal degenerations: hereditary • 687 regeneration  
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