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Henry J. Kaplan, Wei Wang, Jennifer M. Noel, Eric V. Vukmanic, Juan P. Fernandez de Castro, Paul J. DeMarco, Douglas C. Dean, Maureen A. McCall; Photoreceptor Regeneration in a Swine Model of Retinal Damage. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2231. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the ability of swine embryonic retinal progenitor cells to integrate into the outer nuclear layer, differentiate into photoreceptor cells and restore electrophysiologic function in the swine model of iodoacetic acid (IAA) retinal damage.
Three month old domestic swine (n=3) were injected intravenously with 7.5 mg/kg of IAA. Two weeks later dissociated retinal cells from embryonic day 65 (E65) or 85 (E85) swine carrying a GFP transgene were injected subretinally (5x107/ml in a 50 ul bleb) in the visual streak. Clinical examination and electrophysiology (full field ERG [ff-ERG] and multifocal ERG [mf-ERG]) were performed at baseline and at 3, 5, 7 and 12 weeks post-transplant. Enucleated eyes were examined by light microscopy and histochemistry with the confocal microscope.
Four eyes of three IAA-treated swine received retinal progenitor cell transplants - two with E65 cells and two with E 85 cells. Postoperative clinical examination showed mild RPE dispersion in the area of the bleb but was otherwise normal. The ff-ERG was severely reduced following IAA injection and remained reduced following transplantation. In contrast, the mf-ERG which was also reduced prior to transplantation returned towards normal at 3 weeks post-transplant in 3 of 4 eyes before becoming reduced at later time points. Immunohistochemistry revealed the integration of many GFP+ E65 cells into the outer nuclear layer that both expressed cone opsin and had cone photoreceptor morphology with generation of inner/outer segments. In contrast, transplantation of GFP+ E85 cells resulted in the retinal integration of cells that expressed either rhodopsin or cone opsin . Integrated GFP+ cells with cone morphology expressed red/green opsin and recoverin but not rhodopsin. GFP+ cells that expressed rhodopsin, also expressed recoverin, but not cone opsin.
IAA produces selective damage to photoreceptor cells in the swine retina. Subretinal transplantation of E65 retinal progenitor cells results in the preferential differentiation and integration of cone photoreceptors in the ONL, whereas E85 cells generated both rod and cone photoreceptor cells. Transient return of electrophysiologic function was associated with the generation of both inner and outer segments of cone photoreceptor cells.
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