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Katherine Delf, William Cepurna, Diana C Lozano, Elaine Johnson, John C Morrison, Shandiz Tehrani; Systemic Rho kinase inhibition via fasudil does not alter awake daytime intraocular pressure in rats. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3805.
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© ARVO (1962-2015); The Authors (2016-present)
We previously reported that systemic Rho kinase inhibition via fasudil protects optic nerve axons against injury following acute intraocular pressure (IOP) elevation in rats. Two weeks following 8 hours of controlled elevation of IOP (CEI) at 60 mm Hg, axon injury in animals that received systemic fasudil was significantly reduced by 22% relative to animals that received vehicle. Topical Rho kinase inhibitors, such as netarsudil, reduce IOP. To investigate whether the previously demonstrated neuroprotection by systemic Rho kinase inhibition may be due to lowered IOP after the CEI exposure, we assessed daytime IOPs in awake rats undergoing systemic fasudil administration.
Twelve 8-9 month old male Brown Norway rats that were housed in a 12 hour light/dark cycle underwent bilateral awake IOP measurements daily (between 9 and 11 AM) during a 5-day acclimation period using a handheld rebound tonometer (TonoLab; Icare). After acclimation, daily bilateral awake IOPs were measured for 10 additional days in animals undergoing daily fasudil (10 mg/kg/day; n = 6 rats) or vehicle (water; n = 6 rats) intraperitoneal injection. Ten IOP measurements/eye/day were used to calculate a daily mean for each eye. Mean daily IOP ± standard error of the mean (SEM) over the 10 days were calculated for each group and compared using Student’s t-test. Day-to-day IOP means across the testing period were compared between the two groups using linear regression.
Mean awake IOP measurements in the fasudil and vehicle groups averaged over a 10-day period were 22.5 ± 0.1 and 22.3 ± 0.1 mm Hg, respectively (p = 0.36). Linear regression analysis of daily means for both groups across time showed that the y-intercepts and slopes were not significantly different (p=0.3389 and p=0.0529, respectively). In addition, daily IOP means between the fasudil and vehicle groups showed no statistically significant difference between groups.
Systemic Rho kinase inhibition via fasudil does not reduce awake daytime IOP in adult male Brown Norway rats, and awake IOP is stable over time. Thus, the previously reported axon protection after acute IOP elevation by systemic fasudil administration is likely due to an IOP-independent pathway. Further work is currently underway to determine the mechanisms of axon protection against IOP elevation via systemic fasudil administration.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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