Photoreceptor-Like Cells in Transgenic Mouse Eye

^{Department of Ophthalmology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama}

^{Guangzhou First People's Hospital, Department of Ophthalmology of Nansha Central Hospital, Guangzhou, Guangdong, China}

Correspondence: Run-Tao Yan, 1670 University Boulevard, VH 444, Birmingham, AL 35294-0019; ude.bau@naytr.

Shu-Zhen Wang, 1670 University Boulevard, VH 444, Birmingham, AL 35294-0019; ude.bau@gnawzs.

Received 2013 Feb 26; Accepted 2013 Jun 10.

Abstract

Purpose.

Recent success of rescuing vision by photoreceptor replacement in mouse models of photoreceptor degeneration intensifies the need to identify approaches to generate photoreceptors cells for future replacement therapies. We explored the possibility of whether in the mouse eye photoreceptor-like cells could arise from the RPE experimentally manipulated to express a regulatory gene participating in transcriptional networks leading to photoreceptor genesis during retinal development.

Methods.

Transgenic mice were generated with a DNA construct that would express neurogenin1 from RPE bestrophin-1 promoter or neurogenin3 from RPE65 promoter. Transgenic mice were examined with histology and immunohistology for the presence of photoreceptor-like cells and for the presence of cells that might represent transitional stages in RPE-to-photoreceptor reprogramming. Explant culture of “sclera+choroid+RPE” eyecup was used to examine whether cells with photoreceptor traits could arise from the eyecup derived from transgenic mice.

Results.

Transgenic animals showed varied degrees of phenotype manifestation. Approximately 60% of offspring from ∼50% of founders contained photoreceptor-like cells in the subretinal space. These cells expressed photoreceptor proteins recoverin, red opsin, and rhodopsin, and displayed morphologic similarities to photoreceptors. In these eyes, the RPE was maintained. Cells seemingly amid RPE-to-photoreceptor transformation were observed in young and aged mice, suggesting old animals were responsive to the reprogramming scheme. De novo generation of photoreceptor-like cells was detected in “sclera+choroid+RPE” eyecup explants derived from adult animals.

Conclusions.

Our results point to a potential way to generate photoreceptor cells in situ in adult mammalian eyes.

Keywords: photoreceptors, regeneration, reprogramming, mammalian retina

Abstract

Acknowledgments

We thank Jeffrey D. Messinger at the Imaging Center of Department of Ophthalmology, University of Alabama at Birmingham, for his technical assistance on electron microscopy.

Supported by NIH/NEI Grant EY011640, EyeSight Foundation of Alabama Research Grant FY2011-12-276, Research to Prevent Blindness, and NIH/NEI Core Grant P30 EY003039.

Disclosure: R.-T. Yan, None; X. Li, None; S.-Z. Wang, None

Acknowledgments

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