Topical Ripasudil Suppresses Retinal Ganglion Cell Death in a Mouse Model of Normal Tension Glaucoma

Invest Ophthalmol Vis Sci. 2018 Apr 1;59(5):2080-2089. doi: 10.1167/iovs.17-23276.


Purpose: To assess if ripasudil has a neuroprotective effect using mice with excitatory amino acid carrier 1 (EAAC1) deletion (EAAC1 knockout [KO] mice), a mouse model of normal tension glaucoma.

Methods: Topical administration (5 μL/day) of two different concentrations of ripasudil (0.4% and 2%) were applied to EAAC1 KO mice from 5 to 12 weeks old. Optical coherence tomography, multifocal electroretinograms, the measurement of intraocular pressure (IOP), and histopathology analyses were performed at 5, 8, and 12 weeks old. Retrograde labeling of retinal ganglion cells (RGCs), immunoblot, and immunohistochemical analyses of phosphorylated p38 mitogen-activated protein kinase (MAPK) in the retina were performed at 8 weeks old.

Results: Topical ripasudil ameliorated retinal degeneration and improved visual function in EAAC1 KO mice at both 8 and 12 weeks old. Ripasudil reduced IOP and strongly suppressed the phosphorylation of p38 MAPK that stimulates RGC death in EAAC1 KO mice.

Conclusions: These results suggest that, in addition to IOP reduction, ripasudil prevents glaucomatous retinal degeneration by neuroprotection, which is achieved by suppressing cell-death signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Animals
  • Cell Death / drug effects
  • Disease Models, Animal*
  • Electroretinography
  • Excitatory Amino Acid Transporter 3 / genetics
  • Immunoblotting
  • Immunohistochemistry
  • Intraocular Pressure / drug effects
  • Isoquinolines / administration & dosage*
  • Low Tension Glaucoma / drug therapy*
  • Low Tension Glaucoma / metabolism
  • Low Tension Glaucoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology
  • Retinal Degeneration / prevention & control*
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Sulfonamides / administration & dosage*
  • Tomography, Optical Coherence
  • Tonometry, Ocular
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • rho-Associated Kinases / administration & dosage*


  • Excitatory Amino Acid Transporter 3
  • Isoquinolines
  • K-115
  • Slc1a1 protein, mouse
  • Sulfonamides
  • rho-Associated Kinases
  • p38 Mitogen-Activated Protein Kinases