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Henri Lorach, Seungbum Kang, Alix Trouillet, Roopa Dalal, Daniel V Palanker; Long-term survival and integration of the retina/RPE allograft in rat models of retinal degeneration.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5000. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To study the survival and integration of the retina/RPE allografts from healthy young rats into rats with retinal degeneration.
Retina/RPE sheet explants (1mm in diameter) were harvested from wild type Long Evans and Sprague Dawley rats (P25-P70). Recipients were RCS (>P150) and S334ter-3 (>P60) rats after complete photoreceptor degeneration. Optical coherence tomography (OCT) was used to monitor reattachment of the retina and implant survival over time. Integration of the transplant with the host inner retina was assessed after explantation, using histology and immunohistochemistry.
Upon successful surgery, we observed no rejection of the retina/RPE transplant in the subretinal space of degenerated retinas, with all the strains or ages of donors and recipients. Photoreceptors survived only when RPE was included in the transplanted sheet. Based on OCT, the structure of the transplant was preserved during the 5 months follow-up period. Ganglion cell layer completely disappeared, likely due to the cut axons, and the inner plexiform layer thinned-down to about 30% of its initial thickness. However, inner nuclear layer and photoreceptors remained preserved, including up to 6 layers of photoreceptor nuclei with their inner and outer segments. Immunostaining of the rod bipolar cells with PKC alpha, combined with bassoon staining, revealed some evidence of the dendrites sprouting from the host bipolar cells and synaptogenesis to rewire to bipolar cells in the transplant.
We demonstrate the long-term survival of mature retina/RPE transplants in rats with retinal degeneration. Essential for this success was co-transplantation of RPE and minimal trauma during surgery. Surprisingly, the success did not depend on the donor age or strain, as was previously assumed. The morphological indications of reconnection to the host retina will have to be confirmed by electrophysiological recordings.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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