July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Systemic Rho kinase inhibition via fasudil does not alter awake daytime intraocular pressure in rats
Author Affiliations & Notes
  • Katherine Delf
    Oregon Health & Science University, Portland, Oregon, United States
  • William Cepurna
    Oregon Health & Science University, Portland, Oregon, United States
  • Diana C Lozano
    Oregon Health & Science University, Portland, Oregon, United States
  • Elaine Johnson
    Oregon Health & Science University, Portland, Oregon, United States
  • John C Morrison
    Oregon Health & Science University, Portland, Oregon, United States
  • Shandiz Tehrani
    Oregon Health & Science University, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Katherine Delf, None; William Cepurna, None; Diana Lozano, None; Elaine Johnson, None; John Morrison, None; Shandiz Tehrani, None
  • Footnotes
    Support  National Institutes of Health (Bethesda, MD, USA: K08EY024025 to ST, R01EY010145 to JCM, and P30EY010572 to OHSU); Research to Prevent Blindness (New York, NY, USA: Career Development Award to ST and unrestricted grant to OHSU)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3805. doi:
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    • Get Citation

      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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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