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Shu-Zhen Wang, Run-Tao Yan; Photoreceptor regeneration in transgenic mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1456.
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Photoreceptor regeneration in the mammalian eye remains an elusive goal. Our laboratory is investigating the possibility of tweaking the RPE, a tissue with naturally occurring wound healing ability, for photoreceptor regeneration in situ in the eye. The underlying theme is to use a regulatory gene with pro-photoreceptor activity to reprogram RPE cells to initiate photoreceptor differentiation, so as to channel RPE’s well-known capacities of proliferation and plasticity towards photoreceptor production inside the mammalian eye. Previous study showed that transgenic mice (generated with DNA that would express ngn1 or ngn3 in RPE cells driven by PRPE65 or PVMD2) contained photoreceptor-like cells in the subretinal space. This study examines whether new photoreceptor cells could be born in adult transgenic mice.
Adult transgenic mice (Tg) and Tg/rd1 mice (generated by crossing Tg mice with rd1/rd1) received daily intraperitoneal injection of BrdU for 2 weeks. Eyes were then fixed and analyzed with double-immunohistochemistry for BrdU incorporation and photoreceptor protein recoverin.
BrdU+/recoverin+ cells were detected in transgenic mice aging between 7 weeks and 1 year. Most of the double-labeled cells localized within the outer nuclear layer of the periphery retina. Occasionally, double-labeled cells were found to be attached to the RPE or containing dark pigment granules typically present in RPE cells, reminiscent of being in a RPE-to-photoreceptor transitional stage. BrdU+/recoverin+ cells were also detected in 7 week-old and 5 month-old Tg/rd1 mice.
The presence of BrdU+/recoverin+ cells suggests that new photoreceptor cells could be produced in adult transgenic mice, conventional and Tg/rd1.
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