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Y Matsumoto, S Sawaguchi, SL Bernstein; Neuroprotective Efficacy of Different Drug Classes on a Rodent Model of Ischemic Optic Neuropathy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):768.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Anterior ischemic optic neuropathy (AION) is one of a family of ischemic diseases affecting the optic nerve. AION results from blockage of the vascular supply of the anterior portion of the optic nerve resulting in retinal ganglion cell (RGC)-specific death. We previously reported on a new rodent model of AION (Bernstein et al, 2000). This model accurately replicates many of the changes seen in human AION. We wished to model different levels of AION severity, and determine the efficacy of various neuroprotective agent classes in AION. Methods: Animals were handled in accordance with ARVO guidelines. AION was induced according to the previously reported method, with the modification of AION induction time. AION was induced only in the right (experimental) eye, with the left eye used as a control. For analysis of neuroprotection efficacy of different drug classes, we chose nifedipine (NF), a calcium channel blocker, estradiol (ES); an estrogen family member, and aminoguanidine (AG). 2g/kg of AG (N=3 animals), and smaller amounts of NF (N=3 animals) were given as a stat dose, and continuously administered via a 7 day subcutaneous pump (ALZET). ES was given as an intramuscular injection (N=4 animals). All drugs were administered prior to AION induction. RGCs were counted 30-40 days post AION induction to assess increase in RGC survival from drug efficacy. Results: The appearance of the AION-affected nerve appears with pale edema, with time dependency. The percentage of surviving RGCs compared to the control eye linearly varied with the length of AION induction time (r= -0.80; P<0.01). AG pretreatment had only a minimal effect on RGC survival. NF was more effective than AG as neuroprotective agents, with 98.5% and 69.3% RGC survival compared to controls, respectively. Initial analysis of ES data suggests that ES pretreatment may be at least as effective as NF. Conclusion: The correlation of induction time with AION severity further suggests that rodent AION may be a useful tool for neuroprotection analysis, by providing a model with a robust and linear response to disease. Further, optic nerve neuroprotection via calcium-channel induced vascular spasm, rather than by iNOS inhibition, may be effective. Other, non-classical types of neuroprotective agents such as estrogens may be need to be considered for effective treatment of IONs.
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