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Joseph Paul, Zheng He, Christine T Nguyen, James Armitage, Andreas Fouras, Algis J Vingrys, Bang V Bui; Age Increases Susceptibility to Chronic Intraocular Pressure Elevation in Rats. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Age is the strongest risk factor for glaucoma, the reason for which is poorly understood. Older eyes have been shown to exhibit poorer recovery from acute IOP elevation. In this study we considered whether chronic IOP elevation by way of a circumlimbal suture model produces greater functional and structural changes in older rat eyes.
Anaesthetised (isoflurane), 18-month-old male Long Evans rats (n=10) underwent circumlimbal suture application (7/0) in one eye to produce chronic IOP elevation for 15 weeks. Fellow eyes were left untreated as control. IOP was measured at least twice per week for 15 weeks. Electroretinography was performed under anaesthesia (ketamine:xylazine 60:5 mg/kg) at baseline and 2, 4, 8, 12 and 15 weeks after surgery. After 15 weeks retinae were harvested for cell count analysis. Data (mean±SEM) from 18 month rats are compared against 3-month-old (n=7) animals, using t-test, one- and two-way ANOVA where appropriate.
In the older cohort, after a brief IOP spike, IOP was elevated from baseline 13.1±0.9 to 20.5±0.3 mmHg and remained elevated for 15 weeks. IOP elevation was slightly higher in treated young eyes (22±0.5 mmHg, p=0.006).Two weeks after IOP elevation the photoreceptor (P3) response showed a small reduction (85.2±4.6% of baseline p<0.001) that was sustained through the 15 weeks (88.0±3.6%, p=0.49). Bipolar cell mediated (P2) amplitude was also reduced (86.1±3.4%, p<0.001) and showed some recovery (90.9±2.5%, p=0.047). This effect was similar in young and old eyes (two-way ANOVA, p=0.95). The ganglion cell mediated scotopic threshold response (STR) was reduced to 70.4±8.7% of baseline at 2 weeks and showed a progressive decline to 59.4±6.1% after 15 weeks. This STR deficit was greater than the decline in outer retinal dysfunction. More importantly, the STR deficit in older eyes was greater than younger eyes (65.1±6.8%, two-way ANOVA p<0.001).In 18 month old rats, 15 weeks of IOP elevation produced significant reduction in cell density in the ganglion cell layer compared with control eyes (control 1270±60, treated 1033±80 cells/mm2, p=0.024) and young treated eyes (1880±190 cells/mm2, p<0.001). There was no change in photoreceptor density.
Ganglion cell mediated function and cell density was significantly more affected by chronic IOP elevation in older rat eyes when compared to younger eyes.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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