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M. K. Mathews, Y. Guo, S. L. Bernstein; A New Transgenic Mouse Model of Neuroprotection in Ischemic Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2456.
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To determine whether a transgenic mouse strain with the Thy-1 promotor, linked to cyan fluorescent protein (CFP) reporter is an appropriate model for evaluating retinal ganglion cell (RGC) neuroprotective strategies following induction of experimental anterior ischemic optic neuropathy (rAION).
Male transgenic (Tg) Thy-1 (CFP) mice (28-35g) were anesthetized, and rAION induced using the photoembolic method previously described (Goldberg-Cohen, N Guo Y, Margolis F, et al. IOVS 2005; 46: 2716-2725.). Briefly, 2.5mM rose Bengal dye was injected through the tail vein and the optic nerve head exposed to 12 one-second applications of frequency doubled yttrium aluminum garnet (YAG) laser (535nm, 300 microns spot size, 50mW energy). 2 days post-induction, all eyes were examined under anesthesia to determine if optic nerve swelling, indicating successful induction of optic nerve ischemia, was present, and to exclude complications, such as retinal artery occlusion. Then one eye of each animal received 0.75 ug Ciliary Neurotrophic Factor (CNTF) intravitreally in 0.01 ml PBS. Controls included both sham-injected and untreated (naïve) animals. Sham-injected fellow eyes received 0.01 ml PBS intravitreally. On day 14, the animals were sacrificed by Co2 anesthesia and subsequent cervical dislocation; eyes were enucleated, and fixed in 4% paraformaldehyde-PBS. Anterior chambers were removed and the retina carefully dissected out of the eye cup. Retinae were mounted on microscope slides and examined using confocal microscopy.
Induction of rodent ischemic optic neuropathy (rAION) resulted in loss of CFP fluorescence. CNTF and PBS intravitreal injections were well tolerated. The incidence of complications was equal in CNTF - injected eyes and controls. Complications (in ascending order of frequency) included: cataract, subconjunctival hemorrhage, vitreous hemorrhage, and endophthalmitis.
The (Tg) Thy-1 CFP mouse model, coupled to the rAION model system, appears to be appropriate for optic nerve neuroprotection research for NAION. The use of neuroprotective factors currently being considered clinically for other retinal disorders, and injected into the eye after rAION induction, may enable us to evaluate these drugs for their use in clinical post-stroke treatment strategies of ischemic optic neuropathy.
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