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Vicki Chrysostomou, George Y. Kong, Nicole Van Bergen, Ian A. Trounce, Jonathan G. Crowston; Defects in Mitochondrial Respiration Promote Retinal Ganglion Cell Death and Dysfunction after Short-Term IOP Elevation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3074.
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To determine whether mitochondrial dysfunction alters retinal ganglion cell survival and function after short-term IOP elevation.
Xenomitochondrial (Xeno) mice, which have a mild defect in retinal oxidative phosphorylation due to mismatching of nuclear and mitochondrial DNA, were subject to unilateral IOP elevation (50 mmHg for 30 min) at 12 months of age. Age-matched C57BL/6 mice (same background) served as controls. Mice were sacrificed after 1, 3 and 7 days of IOP challenge. Retinal ganglion cell function was assessed prior to sacrifice with the positive scotopic threshold response (pSTR) component of the electroretinogram. Retinas were assessed for cell death using TUNEL and for expression of stress-inducible proteins (GFAP, HO-1) using immunohistochemistry and Western blotting.
In the Xeno strain, pSTR amplitudes were reduced from baseline values following IOP elevation by 91.3±1.2 % at 7 days compared with a reduction of 46.4±8.2% in the C57BL/6 strain (n=10 per strain). At 1 day, there was an increase in TUNEL+ profiles in the retinal ganglion cell layer in both strains, however, the increase was significantly greater (4.2-fold, P=0.0052) in Xeno retinas compared to C57BL/6 retinas (n=5 per strain). This was accompanied by an upregulation of GFAP and HO-1 expression in retinal Müller cells. No TUNEL+ cells were detected in non-IOP challenged fellow eyes of either strain.
Retinal ganglion cells in mice with defective mitochondrial respiration suffered greater functional and structural damage in response to IOP elevation compared to control mice. These findings indicate that mitochondrial dysfunction increases the susceptibility of retinal ganglion cells to injury.
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