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Robert B. Aramant, Bryan W. Jones, Magdalene J. Seiler, Pamela B. Yang, Hans S. Keirstead, Robert E. Marc; Visual Restoration And Circuitry - Retinal Sheet Transplants To Rats With Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4023.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate cell types and connectivity of long-term fetal retinal sheet transplants to a degenerating retina.
S334ter line 3 rats received retinal sheet transplants at the age of 24-40d. Donor retinas were derived from E19 rats expressing human placental alkaline phosphatase (hPAP). Eight selected transplants were recorded in the superior colliculus (SC) 129-162d after surgery. Thirteen selected rats were fixed up to 265 days after surgery. Selected vibratome sections through the transplant area were embedded in Eponate, sectioned into serial ultrathin datasets and probed for rhodopsin, cone opsin, CRALBP, DAPI and antibodies against IgGs targeting, L-glutamate, L-glutamine, glutathione, glycine, taurine, and GABA.
Transplanted rats showed visual responses in a transplant-specific area of the SC, but not outside this area. No responses were found in RD controls. Rod and cone opsin immunoreactivity was demonstrated in large transplant areas with photoreceptor outer segments in contact with host RPE. No such staining was found in the degenerated host retina. The transplant edges and the host retina demonstrated extensive remodeling. The transplant inner nuclear layer showed loss of neurons, e.g. bipolar cells, but amacrine cells and horizontal cells were not reduced, and remaining cell populations appeared healthy. In many areas, glial hypertrophy between the host and transplant was absent and host and transplant plexiform layers intermingled.
Both amacrine (glycinergic and GABAergic) and horizontal cells are potentially involved in a novel circuit between fetal retinal sheet transplants and host which contributes to the restoration of visual responses.
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