Axonal Injury Following A Controlled Elevation of Intraocular Pressure (IOP) is Greater in Elderly than in Adult Rat Optic Nerves

Abstract

Purpose : Age is a significant risk factor for glaucoma. Vascular and other physiological changes associated with aging may play a significant role in the progression of this disease. This study compared optic nerve injury in aged rats (24 months) to that in adult rats (8-10 months) following exposure to an interval of controlled elevation of IOP (CEI).

Methods : Brown Norway rats (N= 16 aged and 49 adults) were anesthetized and underwent unilateral anterior chamber cannulation to elevate IOP to 60 mm Hg for 8 hours. During CEI, vital signs, O₂ saturation, heart rate, and blood pressure were monitored. Hourly means (±SEM) for each physiological parameter were calculated. Animals were sacrificed and globes were perfusion-fixed with buffered glutaraldehyde 2 weeks after CEI, and graded for injury on a scale from 1 (normal) to 5 (>50% of axons degenerating). Physiologic parameters were compared between the groups with two-way ANOVA followed by Sidak’s multiple comparison test.

Results : Aged CEI nerves (N=16) had a significantly greater injury grade (1.86 ± 0.32) than both aged control nerves (1.04 ± 0.02; P < .0001) and adult CEI nerves (1.45 ± 0.06; P = .03; N=49). Mean arterial pressure was 18 mm Hg lower (P < .0001) in aged animals (82 ± 3 mm Hg) than adult animals (100 ± 3 mm Hg; N=28), but was not correlated with nerve injury (r² = 0.1). Additionally, 25% of CEI aged nerves had injury grades above the 95% confidence interval (1.18 to 2.53) for the group. These 4 aged animals had heart rates (285 ± 12 vs. 300 ± 5 beats-per-minute; P = 0.17), breathing rates (70 ± 4 vs. 66 ± 5 breaths-per-minute; P = .99), and O₂ saturations (99 ± 0.1 vs. 99 ± 0.3%; P < 0.99) that were similar to the other 12 aged animals in the group.

Conclusions : Aged rat optic nerves have higher susceptibility to axonal injury following exposure to elevated IOP than adult optic nerves. Within the aged group, increases in injury were not correlated with differences in arterial pressure or other measured systemic physiological parameters, possibly indicating other inherent factors may be responsible for the differences seen in some aged animals.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.