Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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).
Conclusions: :
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.
Keywords: aging • oxidation/oxidative or free radical damage • electroretinography: non-clinical