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J. Gust, T. A. Reh; Mature Rod Photoreceptors Integrate Into the Outer Nuclear Layer of Adult Recipient Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5145.
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Cell-based therapy has been investigated as a possible cure for photoreceptor degenerations. Recent work has shown that early postmitotic rod photoreceptors are able to integrate into the adult outer nuclear layer from a subretinal transplant (MacLaren et al., 2006), while undifferentiated progenitors, or mature photoreceptors were not. To determine what property of early postmitotic rods conveyed this unique ability to act as donors, we developed a system for directly comparing the suitability of donor cells from different ages for transplantation, which circumvents inter-experimental variation and differences in survival for donor cells of different ages.
Retinas from GFP+ and td-tomato +/+ mice at different ages were dissociated together, and transplanted into the subretinal space of adult recipient mice. One of the donor retinas was always of the reference age P5, the other ranging from E16 to P30. The recipient eyes were harvested after 14 days, fixed and sectioned. We then counted the integrated red and green fluorescent cells in the ONL, as well as grafted photoreceptors surviving in the subretinal space.
Consistent with earlier studies, we found that the rods from early postnatal animals had the best ability to integrate into the host outer nuclear layer following subretinal transplantation; however, in contrast to prior reports, we found that donor rod photoreceptors of up to P30 were able to integrate. The effectiveness of integration and survival of the rods in the subretinal space were both correlated with the age of the donor, suggesting that the enhanced effectiveness of neonatal rods for integration following subretinal transplantation is due to their increased ability to survive the procedure.
Mature rod photoreceptors have the ability to integrate into the host retina. The decrease in their efficiency may at least partially be explained by a decrease in survival.
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