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K. Narfstrom, R.B. Aramant, M.W. Seeliger, R. Bragadottir, M. Mahoney, M.J. Seiler; Functional and Structural Assessment of Retinal Sheet Allograft Transplantation in Feline Hereditary Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4144.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To show whether intact sheets of fetal BDNF treated allografts integrate into the dystrophic retina of the Abyssinian cat with slowly progressive rod cone degeneration. Methods: Retina was dissected from cat fetuses of gestational day 42. Pieces (1.7 x 3mm) were incubated with BDNF microspheres in hibernation medium on ice 4–6 hours, and unilaterally transplanted as sheets to the subretinal space of 4 cats, age 1–2 years, at an early disease stage, using vitrectomy and a custom–made implantation tool. Cats were studied by ophthalmoscopy, bilateral full–field flash ERGs, indocyanine and fluorescein angiograms up to 4 months following surgery, euthanized and eyes fixed in 4% paraformaldehyde. Frozen sections of E42 donor and transplanted eyes were stained with antibodies for retinal markers (recoverin, rhodopsin, PKC, MAP 1A, calbindin, calretinin, synaptophysin, glutamine synthetase). Results: Funduscopy and angiography showed good integration of transplants and some scarring in the host retinas. Using ERG no differences in wave–forms, response amplitudes or implicit times between transplanted and contralateral eyes were found. In 2 of the 4 cats, Bruch's membrane had been damaged, and only remnants of donor tissue were found. In the other 2, intact laminated transplants were found in the subretinal space. The host retina still contained 6–7 rows of photoreceptors in the outer nuclear layer outside the transplant area. Within the transplant area, most host photoreceptors had disappeared. Transplants were well integrated within the host neural retina, and their photoreceptor outer segments made normal contacts with the host RPE. Transplants stained for all studied cellular markers, including PKC which was not found in the E42 donor tissue. Conclusions: Intact fetal sheet transplants pretreated with BDNF can integrate well within a degenerating cat retina and develop good lamination. Although these studies showed neuroretinal integration, no objective functional improvement was demonstrated by ERG. Host–transplant integration and functional effects need to be further evaluated using longer follow–up times, preferably in cat host retinas with a more advanced retinal degeneration.
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