April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
A Selective Inhibitor of Drp1, Mdivi-1, Increases Retinal Ganglion Cell Survival in Acute Ischemic Mouse Retina
Author Affiliations & Notes
  • S. Park
    The Sophie and Arthur Brody Optic Nerve Laboratory, Hamilton Glaucoma Center and Department of Ophthalmology, University of California San Diego, La Jolla, California
    Department of Ophthalmology, Chonnam National University Medical School, Gwangju, Republic of Korea
  • J. D. Lindsey
    The Sophie and Arthur Brody Optic Nerve Laboratory, Hamilton Glaucoma Center and Department of Ophthalmology, University of California San Diego, La Jolla, California
  • R. N. Weinreb
    The Sophie and Arthur Brody Optic Nerve Laboratory, Hamilton Glaucoma Center and Department of Ophthalmology, University of California San Diego, La Jolla, California
  • W.-K. Ju
    The Sophie and Arthur Brody Optic Nerve Laboratory, Hamilton Glaucoma Center and Department of Ophthalmology, University of California San Diego, La Jolla, California
  • Footnotes
    Commercial Relationships  S. Park, None; J.D. Lindsey, None; R.N. Weinreb, None; W.-K. Ju, None.
  • Footnotes
    Support  NIH grant R01 EY018658
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3189. doi:https://doi.org/
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      S. Park, J. D. Lindsey, R. N. Weinreb, W.-K. Ju; A Selective Inhibitor of Drp1, Mdivi-1, Increases Retinal Ganglion Cell Survival in Acute Ischemic Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3189. doi: https://doi.org/.

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

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Abstract

Purpose: : To determine whether acute intraocular pressure (IOP) elevation alters dynamin-related protein 1 (Drp1) as well as whether a selective inhibitor of Drp1, mdivi-1, can block apoptotic cell death and subsequently increase retinal ganglion cell (RGC) survival in ischemic mouse retina.

Methods: : C57BL/6 mice received injections of mdivi-1 (50 mg/kg) or vehicle and then transient retinal ischemia was induced by acute IOP elevation. RGC survival was measured after FluoroGold labeling. Drp1, optic atrophy type 1 (OPA1) and glial fibrillary acidic protein (GFAP) protein expression and distribution were assessed at 12 hours after ischemia by Western blot and immunohistochemistry. Apoptotic cell death was assessed by TUNEL staining.

Results: : Drp1, OPA1 and GFAP protein expression were significantly increased in the early neurodegenerative events (within 12 hours) of ischemic mouse retina. Mdivi-1 treatment blocked apoptotic cell death in ischemic retina, and significantly increased RGC survival at 2 weeks after ischemia. Further, mdivi-1 treatment did not change Drp1 protein expression but significantly decreased OPA1 and GFAP protein expression. Both isoforms of OPA1 protein (80- and 90-kDa) were significantly decreased in mdivi-1-treated ischemic retina.

Conclusions: : These findings suggest that altered Drp1 and OPA1 activity following acute IOP elevation may be an important component of a biochemical cascade leading to RGC death in ischemic retina. Thus, these results support further studies to determine whether pharmacological inhibition of Drp1 by mdivi-1 may provide a novel mechanism to protect RGCs against pressure-related ischemic damage in glaucoma.

Keywords: neuroprotection • retina: neurochemistry • retina: proximal (bipolar, amacrine, and ganglion cells) 
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