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K. M. Warre Cornish, A. C. Barber, J. C. Sowden, R. R. Ali, R. A. Pearson; Kinetics of Integration Following Transplantation of Photoreceptor Precursors Into Adult Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5245.
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Transplantation of photoreceptors offers a potential therapy for irreversible retinal degenerations, which are a leading cause of blindness in the Western world. Understanding the kinetics of donor cell migration and integration will allow refinement of strategies to improve their integration, ultimately aiding the progress of photoreceptor transplantation towards clinical utility. Knowledge of the timing of photoreceptor integration will allow administration of agents to enhance cell migration, or the disruption of barriers to entry, such as the outer limiting membrane, to be timed to coincide with the peak of transplanted cell integration.
Neural retinas from post-natal (P) day 4 Nrl.GFP mice were dissociated enzymatically. Nrl.GFP+ve rod precursors were sorted by FACS and transplanted into the subretinal space of adult wild type mice of 6 - 8 weeks of age. Recipient animals were sacrificed at various time points from 24 hours to 2 weeks after transplantation. Eyes were fixed and processed for cryosectioning and immunohistochemistry. Transplanted cells were assessed morphologically and immunohistochemically using confocal microscopy.
The majority of transplanted rod precursor cells migrated into the recipient retina between 96 hours and 1 week post injection. Morphologically differentiated profiles were observed between 1 and 2 weeks post injection. Rod precursor cells migrating away from the transplanted cell mass were often observed as having a unipolar morphology with a single leading process.
Transplanted photoreceptors become integrated within the recipient retina after a delay of approximately 4 - 5 days. Further detailed assessment of the morphologies assumed by migrating donor cells should provide information regarding the migratory mechanisms used by these cells, which may be useful in designing strategies to enhance transplanted photoreceptor integration.
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