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G. Barnes, B. Li, I.–H. Pang, D. Cantu–Crouch, A. Clark, W.F. Holt; Optic Nerve Damage Score – a Simple, Efficient, and Reliable Endpoint for Experimental Optic Neuropathy . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1315.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine whether the optic nerve damage score (ONDS), a simple histological endpoint measure, can be used to estimate retinal ganglion cell (RGC) loss caused by the transient global ocular ischemia/reperfusion (I/R) model.Methods: In Brown Norway rats, right eyes were subjected to transient periods of ischemia of 45, 60, or 75 min, by increasing the intraocular pressure (IOP) above systolic blood pressure (i.e. > 130 mm Hg). Two endpoints, morphologic scoring of optic nerve damage (by masked readers) from p–phenylenediamine–stained optic nerve cross sections and quantification of the dextran tetramethylrhodamine (DTMR) labeled RGCs in whole mounted retinas, were used to assess the degree of I/R induced damage. Results: Two weeks after 45, 60, or 75 min of retinal ischemia followed by reperfusion, the ONDS (ranges from 1 for a normal optic nerve to 5 for global nerve damage) was 1.7 ± 0.1 (N=7), 3.1 ± 0.2 (N=12), or 3.9 ± 0.1 (N=7), respectively. Meanwhile, loss of DTMR–labeled RGCs was 23 ± 10% (N=7), 47 ± 5% (N=11), or 72 ± 5% (N=6), respectively. Both ONDS and RGC counts correlated highly significantly (P < 0.001) with ischemia duration. Pretreatment with MK801 (1 mg/kg, ip, 1 h prior to a 60–min ischemia) significantly reduced the ONDS (1.6 ± 0.1, N=10) and RGC loss (26%, N=4) when compared to the vehicle–treated animals. Conclusions: The ONDS is a simple and reliable endpoint measure that can be used to evaluate neuroprotective drug efficacy and provides similar efficacy data when compared to RGC loss from counting fluorescent labeled RGCs. The ONDS is a particularly useful endpoint measure for drug screening of compounds for retinal protection.
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