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M. K. Mathews, A. Hunter, III, S. L. Bernstein; Neuroprotective Effect of Ciliary Neurotrophic Factor (CNTF) in a Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1447.
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© ARVO (1962-2015); The Authors (2016-present)
To determine whether Ciliary Neurotrophic Factor (CNTF) exerts a neuroprotective effect in a mouse model of Anterior Ischemic Optic Neuropathy (AION) - rodent-AION (rAION).
Male transgenic mice with the Thy-1 promoter, linked to cyan fluorescent protein (CFP) reporter ((Thy-1 (CFP) mice), (28-44g) were anesthetized, and AION was induced using a previously described experimental method - rodent AION (rAION) (1). Then one eye of each animal received an intravitreal injection of 0.75µg Ciliary Neurotrophic Factor (CNTF), which has been widely shown to protect retinal ganglion cells after injury (2). Controls included both sham-injected and untreated animals. Sham-injections consisted of 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; The retina was dissected out of the eye cup and mounted on microscope slides. CFP- fluorescent retinal ganglion cells (RGC's) were imaged using confocal microscopy. The amount of RGC loss was determined by averaging the number of RGC's counted in 12 randomly selected 200µ2 fields in each retina (400x magnification). Average RGC numbers and standard deviations were calculated using the Student's t-test. The percentage of lost RGC's was calculated for each treatment group.
After rAION induction, eyes treated with PBS only lost 55.7% of RGC's when compared to controls. The CNTF- treated eyes lost an average of 36.8% of RGC's when compared to controls. Therfore, CNTF injection resulted in an 18.9% decrease of RGC loss, when compared to PBS after rAION induction.
The rodent model of AION and neuroprotection mimicks the actual clinical events in AION by selectively targeting the vasculature of the optic nerve head. Introduction of the neuroprotective factor after the ischemic event models the sequence of clinical disease followed by intervention more accurately than if CNTF were introduced in the eye before induction of ischemia. Preliminary data indicate that CNTF exerts a neuroprotective effect in sudden optic nerve ischemia. This model enables evaluation of neuroprotective factors in clinical post-stroke treatment in ischemic optic neuropathy.
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