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Xin Xia, Yiwen Li, Zhengying Wang, Lingyu Luo, Rong Wen; Oncostatin M Protects Retinal Ganglion Cells in an Optic Nerve Crush Mouse Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6588.
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Oncostatin M (OSM) is a member of the IL-6 family of cytokines, which includes interleukin 6 (IL-6), IL-11, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), cardiotropin 1 (CT-1), and cardiotrophin-like cytokine (CLC). We have shown previously that OSM protects rod and cone photoreceptors in the transgenic rat that carries the rhodopsin S334ter mutation. In the present work, we studied the neuroprotective effects on retinal ganglion cells (RGCs) after optic nerve crush (ONC) in mouse.
BALB/C mice were used in all experiments. RGCs were retrogradely labeled 7 days before ONC by placing a small piece of gelform containing 3µl of 2% FluoroGold on the surface of the superior colliculi on both sides of the brain. The left optic nerve was exposed from the superior side and crushed by a pair of self-closing forceps (RS-5027, Roboz Surgical Instrument Co., Gaithersburg, MD) for 4 second. The right optic nerve was exposed but not crushed to serve as a sham-operated control. Intravitreal OSM (3µg in 2µl PBS) or PBS (2µl) was given immediately after ONC. Retinas were collected 14 days after, flat-mounted, and examined by the confocal microscopy. Three rectangular areas of 0.64 x 0.64 mm at 0.5, 1.0, and 1.5 mm from the optic nerve disc (OND) in the central region of each retinal quadrant (superior, nasal, inferior and temporal) were examined and the average cell densities were presented as mean±SD/mm2.
RGCs in the sham-operated control retinas are 3,176.46±440.77, 3,062.29±371.21, and 2708.85±303.10 at 0.5, 1.0, and 1.5 mm from OND, respectively (n=6). In PBS-treated retinas, the RCG densities are 402.5±37.73, 397.29±38.95, and 363.33±23.21 at 0.5, 1.0, and 1.5 mm from OND respectively (n=6). RGC densities in OSM-treated retinas are 1,224.90±142.57, 1,311.77±114.21, and 1,182.08±98.00 at 0.5, 1.0, and 1.5 mm from OND, respectively (n=6). RGC densities in OSM-treated are significantly higher than those in the PBS-treated retinas (P<0.001, triple asterisks).
OSM treatment significantly protected RGCs from optic nerve crush induced cell death.
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