July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Systemic Rho Kinase Inhibition Reduces Optic Nerve Axon Injury in Response to Controlled Elevation of Intraocular Pressure in a Rat Model
Author Affiliations & Notes
  • Katherine Delf
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • William Cepurna
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Tiffany E. Choe
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Diana C Lozano
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Elaine C. Johnson
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • John C Morrison
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Shandiz Tehrani
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Katherine Delf, None; William Cepurna, None; Tiffany Choe, None; Diana Lozano, None; Elaine Johnson, None; John Morrison, None; Shandiz Tehrani, None
  • Footnotes
    Support  NIH-R01EY010145, NIH-R01EY010145-S1, NIH-T32EY023211, NIH-K08EY024025, RPB Career Development Award, NIH-P30EY01572, and an unrestricted grant from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3707. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Katherine Delf, William Cepurna, Tiffany E. Choe, Diana C Lozano, Elaine C. Johnson, John C Morrison, Shandiz Tehrani; Systemic Rho Kinase Inhibition Reduces Optic Nerve Axon Injury in Response to Controlled Elevation of Intraocular Pressure in a Rat Model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3707.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Systemic Rho kinase inhibition has been shown to enhance axon survival via astrocyte stabilization in several brain injury models. This study investigates whether systemic Rho kinase inhibition via fasudil administration reduces optic nerve axon injury in response to acute intraocular pressure (IOP) elevation in rats.

Methods : Brown Norway male rats received daily intraperitoneal injections of fasudil (10mg/kg/day) (n=8) or vehicle (n=8) 1 day prior to and for 2 weeks following unilateral IOP elevation. Controlled elevation of IOP (CEI) at 60 mm Hg for 8 hours was performed under 2.25% isoflurane anesthesia, using anterior chamber cannulation connected to a reservoir containing balanced salt solution. Animals were perfusion fixed with buffered glutaraldehyde 2 weeks post-CEI, and both CEI-treated and fellow optic nerves were embedded in plastic and sectioned. Optic nerve axon injury was graded on a scale of 1 (no injury) to 5 (>50% axons degenerating) by 6 masked observers. Mean injury grades were analyzed using 2-way ANOVA.

Results : As expected, CEI treatment in the presence of vehicle produced significant axon injury relative to fellow optic nerves (mean injury grades of 1.44 ± 0.11 [SEM] vs 1.02 ± 0.01, respectively, p<0.01). By contrast, axonal injury following CEI in animals receiving systemic fasudil was reduced compared to vehicle-treated eyes (injury grade 1.19 ± 0.08 vs 1.44 ± 0.11, respectively, p=0.05). Axonal injury following CEI in the presence of fasudil (injury grade 1.19 ± 0.08) was not significantly different from fellow eyes in either fasudil- or vehicle-treated animals (injury grades 1.03 ± 0.02 and 1.02 ± 0.01, respectively).

Conclusions : In this preliminary study, daily administration of a systemic Rho kinase inhibitor reduced optic nerve axon injury following acute IOP elevation in a rat model. Further research is underway to determine the cellular mechanism of this protection.

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

 

The effect of systemic fasudil on optic nerve injury following controlled elevation of intraocular pressure (CEI).

Mean optic nerve axon injury 2 weeks post CEI (intraocular pressure elevated to 60mm Hg for 8 hours) in the presence of the systemic Rho kinase inhibitor fasudil or vehicle in a rat model. Mean injury grades and standard errors of the means are shown (n = 8 per group). Statistical analysis was performed using 2-way ANOVA.

The effect of systemic fasudil on optic nerve injury following controlled elevation of intraocular pressure (CEI).

Mean optic nerve axon injury 2 weeks post CEI (intraocular pressure elevated to 60mm Hg for 8 hours) in the presence of the systemic Rho kinase inhibitor fasudil or vehicle in a rat model. Mean injury grades and standard errors of the means are shown (n = 8 per group). Statistical analysis was performed using 2-way ANOVA.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×