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M. Hosoi, Y. Shinohara, C. Taki, M. Nakatani, K. Ohtsuki, S. Nishimura; Intravitreal Transplant of Müller Cells Promote the Survival of Retinal Ganglion Cells in a Rat Model of Optic Nerve Injury. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3287.
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© ARVO (1962-2015); The Authors (2016-present)
Müller cells, which are the predominant glial element in the retina, appear to play an important role for the survival of retinal ganglion cells (RGCs). In the present study, we investigated if the intravitreally-transplanted Müller cells protect RGCs from death induced by optic nerve (ON) injury.
Müller cells were isolated from retinas of 14-day-old Wistar/ST rats. After cultivation and labeling with 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate (DiI), approximately 4 × 105 cells were injected into the vitreous bodies of syngeneic adult rats bilaterally. The control group was injected with the serum-free medium (vehicle). Three days after the transplant, crushing injuries were made in the ON of right eyes by applying a vessel clip. All rats were euthanized after two weeks. Flatmounts were prepared to determine surviving RGC densities by counting Fluorogold-labeled cells in standardized areas of each retina. Frozen sections were processed for immunohistochemistry.
In eyes with ON injury, the Müller cell injection resulted in survival of more RGCs (2154 +/- 301 /mm2) compared with the control group (1717 +/- 363 /mm2). In eyes without ON injury, RGC densities were similar between the Müller cell-injection and control groups (Müller cell-injection: 2487 +/- 232 /mm2 vs. control: 2469 +/- 165 /mm2). Immunohistochemical analysis revealed that an increase in expression of glial fibrillary acidic protein (GFAP) Müller cell-transplanted retinas or ON-injured retinas. Transplanted Müller cells were immunoreactive for glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in the host eye.
Transplanted Müller cells could survive and express trophic factors in the host eye. Our results suggest that intravitreal transplant of Müller cells protect RGCs from death induced by optic nerve injury.
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