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Li Guo, Benjamin M Davis, Shereen Nizari, Eduardo Maria Normando, Joana Margarida Galvao, Lisa Turner, Jingwei Shi, Melanie Clements, Simona Parrinello, M Francesca Cordeiro, ; Direct optic nerve sheath (DONS) transplantation of Schwann cells reduces RGC death after optic nerve injury. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2439.
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Cell-based therapies are increasingly recognized as a potential strategy to treat retinal degenerative disease. Their administration however, is normally indirect and complex. The aims of this study are to develop a new approach to applying Schwann cells (SCs) directly to the optic nerve sheath (SC/DONS) in a glaucoma-related rat model, and to assess therapeutic effects on protection of retinal ganglion cells (RGCs), compared to SC intravitreal administration (SC/IVT).
Dark Agouti (DA) rats had partial optic nerve transection (pONT) performed in the left eye. SCs were transplanted either directly to ON sheath (SC/DONS) or intravitreally (SC/IVT), with 2.5µl of 2x108 cells/ml and 5 µl of 2.5x108 cells/ml, respectively. Animals that had pONT done without SC treatment served as control. Animals (n = 4-10 per treatment) were sacrificed at 3, 7, 14, 21, and 56 days following pONT, and retinal whole-mounts were dissected and stained with Brn-3a for RGCs. To automatically count RGCs in the entire retina, a novel algorithm count was developed using ImageJ and compared to the manual count. The effects of SCs on targeting primary and/or secondary degeneration were also assessed.
The algorithm count of RGCs in whole retina was significantly correlated to manual count (Pearson’s correlation coefficient = 0.9860, p<0.0001, R2 = 0.9722), with the total number of RGCs being 80,818±4919 and the RGC density 2152±526 cells/mm2 in normal rat retina. Longitudinal profiles of RGC loss in pONT only rats was best fitted to a one phase exponential decal model. Although both SC/DONS and SC/IVT altered the temporal course of pONT-induced RGC degeneration, SC/DONS resulted in delayed but significantly (p<0.01) prolonged duration of RGC protection, compared to SC/IVT treatment.
SC/DONS is a new method of SC administration which appears to have potential in the treatment of optic neuropathies such as glaucoma. The protective effects of SCs are associated with targeting secondary degeneration, with implications for translating cell-based therapies to the clinic.
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