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Y. Li, C.L. Schlamp, R.W. Nickells; Variable Susceptibility of Ganglion Cells to Optic Nerve Crush in Inbred Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1131.
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Purpose: The relationship between intraocular pressure (IOP) and glaucoma is not absolute. Some patients with ocular hypertension never develop glaucoma, while others with normal IOP do. One hypothesis is that susceptibility of ganglion cells to apoptotic stimuli is a function of genetic background. This relationship can be studied using an optic nerve crush model of RGC death in inbred lines of mice. Methods: Fifteen inbred mouse strains (DBA/2J, 129X1/SvJ, C57BL/10J, DBA/1J, C57BL/6J, MRL/MpJ, A/J, FVB/NJ, CBA/CaJ, LG/J, SJL/J, NZB/BINJ, NOD/LtJ, C3H/HeJ, BALB/cByJ) were used in an initial screen of susceptibility. Optic nerve crush was performed on the left eyes of mice with each genetic background for 3 seconds to induce the cell death. Right eyes served as undamaged controls. After two weeks mice were sacrificed and whole mounted retinas were Nissl-stained. Images from each retinal quadrant were digitized and counted using Image-Pro Plus software. Cell loss was determined as a percentage of the cell number in the control eye of each mouse. Significant differences between strains were determined by Student t-tests. Results: In control eyes, cell number ranged from 1992 to 2757/0.33 mm2, with a mean of 2296 ± 218.8 (sd). The percentage of cells lost in crush eyes ranged from 47.7 ± 4.7% (BALB/cBYJ) to 26.3 ± 13.1% (DBA/2J). Based on t-tests comparing strains, 3 classes of susceptibility were designated. BALB/cByJ, C3H/HeJ, and NOD/LtJ strains had significantly higher susceptibility to optic nerve crush (range 47.4 to 42.1% cell loss). NZB/BINJ, SJL/J, LG/J, CBA/CaJ, and FVB/NJ strains exhibited moderate susceptibility (range 40.5 to 35.2%). DBA/2J, 129X1/SVJ, C57BL/10J, DBA/1J, C57BL/6J, MRL/MPJ, A/J were grouped as resistant mice (range 34.6 to 26.3%). Preliminary evaluation shows no correlation between susceptibility and the cell density in the ganglion cell layer of control eyes. Conclusions: Our analysis suggests that genetic background contributes to RGC susceptibility to optic nerve crush. We are continuing to examine the susceptibility of mice resulting from BALB/cByJ x DBA/2J crosses.
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