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M. Nakatani, M. Hosoi, Y. Shinohara, C. Taki, M. Hirabayashi, S. Nishimura; Long-Term Changes in Rat Eyes After Intravitreal Transplantation of Cultured Müller Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4288.
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© ARVO (1962-2015); The Authors (2016-present)
Intravitreally-transplanted Müller cells are likely to protect retinal ganglion cells from death induced by optic nerve (ON) injury (Hosoi, ARVO 2007). This study was to morphologically examine the fate of transplanted Müller cells as well as their effects on the host eye.
Müller cells were isolated from retinas of 14-day-old Wistar/ST rats. After being cultivated and labeled with the lipophilic fluorescent dye (PKH26), approximately 4 × 105 cells were injected into the vitreous bodies of syngeneic adult rats bilaterally. Three days after the transplant, ON injuries were made in the right eyes by applying a vessel clip. Rats were euthanized at 2, 4, 13 and 26 weeks after the clamping. Paraffin-embedded and frozen sections were processed for hisotopathological examination and immunohistochemistry. Retinal flat-mounts were also prepared and examined for the distribution of transplanted cells.
The majority of transplanted cells existed in the form of clots attached on the lens posterior capsule or into the vitreous cavity, while some cells were seen on the retinal surface. The cells on the lens posterior capsule formed a fibrocellular membrane by 2 weeks after transplantation. The cells on the retinal surface distributed over more than half of the area, frequently accumulating in the optic papilla and along major blood vessels. These cells survived for 26 weeks although they gradually decreased in their numbers. Localized retinal detachment occurred in 2 eyes (12.5%) without ON injury and in 6 eyes (37.5%) with ON injury between 2 and 26 weeks after transplantation. Immunohistochemistry revealed enhanced expression of the glial fibrillary acidic protein (GFAP) from 2 to 26 weeks after transplantation.
Transplanted Müller cells remained alive in the vitreous cavity or on the retinal surface, and activated the host retina at least for 6 months. Phenotypic changes of the cells into fibrous membranes were found on the lens capsule as well as along vitreous fibrils. Such changes not only cause lens opacity, but may also be inducing tractional retinal detachments.
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