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Y. Kong, B. V. Bui, I. A. Trounce, A. J. Vingrys, J. G. Crowston; Age-Related Susceptibility of Retina and Optic Nerve to Intraocular Pressure Injury. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3088.
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Aging is a major risk factor for glaucoma but the pathophysiology underlying this is not well understood. We therefore investigated whether aging increases retinal ganglion cell vulnerability to intraocular pressure(IOP)-induced oxidative stress in-vivo.
Acute IOP elevation (50 mmHg for 30 minutes) was induced via anterior chamber cannulation in anesthetized (ketamine:xylazine) wild-type C57/BL6 mice from the following cohorts: (i) 3 month old mice n = 8 (ii) 12 month old mice n=10 and (iii) 18 month old mice n =10. The dark adapted scotopic electroretinogram (ERG) was measured before, during and after IOP challenge. Signals were collected at dim and bright intensities (-4.54 and -2.23 log cd.s.m-2) and analyzed in terms of ganglion cell (positive scotopic threshold response, pSTR) and ON-bipolar cell (P2) responses. Statistical analysis of ERG responses (challenged/baseline %) across time was performed using ANOVA. Retina and optic nerves were collected and analyzed for markers of oxidative stress by Western blot.
In response to IOP challenge, increasing age was associated with increased susceptibility to IOP challenge. 18 month old mice showed significantly greater ganglion cell (pSTR) dysfunction (p=0.004) and slower recovery (p<0.001) compared with 3 month old mice. 18 month old mice also showed significantly greater ON-bipolar cell (P2) impairment with IOP challenge (p=0.05) and slower recovery (p<0.001) compared with 3 month old mice. One hour following IOP challenge, ganglion cell function for 3 month old and 18 month old mice was 70±19% and 28±7% of baseline respectively. Oxidative stress markers HO-1 and HNE in retinal and optic nerve tissues of 18 month old mice were significantly higher than for 3 month old mice (182±47% vs 100±30%, p=0.012).
These data indicate that aging increases retina and optic nerve vulnerability to IOP elevation and associated oxidative stress, and suggests a possible mechanism whereby aging predisposes to glaucoma.
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