June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Endothelin-1 mediated decline in mitophagy in retinal ganglion cells contributes to neurodegeneration during ocular hypertension in rats
Author Affiliations & Notes
  • Bindu Kodati
    Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Renuka M. Chaphalkar
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Gretchen Annika Johnson
    Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Dorota Luiza Stankowska
    Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Raghu R Krishnamoorthy
    Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Footnotes
    Commercial Relationships   Bindu Kodati None; Renuka M. Chaphalkar None; Gretchen Johnson None; Dorota Stankowska None; Raghu Krishnamoorthy None
  • Footnotes
    Support  NIH Grant EY028179
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2974 – F0215. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Bindu Kodati, Renuka M. Chaphalkar, Gretchen Annika Johnson, Dorota Luiza Stankowska, Raghu R Krishnamoorthy; Endothelin-1 mediated decline in mitophagy in retinal ganglion cells contributes to neurodegeneration during ocular hypertension in rats. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2974 – F0215.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The vasoactive peptide, endothelin-1 (ET-1) has been shown to be elevated both in the aqueous humor and circulation of primary open angle glaucoma patients as well as in animal models of glaucoma. ET-1 administration in rodents has been shown to produce neurodegeneration of retinal ganglion cells (RGCs) and their axons. However, the precise mechanisms underlying these effects are still not completely known. The purpose of the study was to assess mitophagic changes during ET-1 mediated neurodegeneration of RGCs in culture as well as in the Morrison model of ocular hypertension in rats.

Methods : Primary RGCs isolated from rat pups were treated with either vehicle or ET-1 (100 nM) for 24 h. Mitophagic changes were determined by assessing the extent of co-localization of LC3B (a marker of autophagosomes) and TOM20 (mitochondrial marker). Mitophagy was also evaluated in the cultured RGCs by treating with MitoTracker (a label for mitochondria) and LysoTracker (a label for lysosomes in live cells). To confirm these findings in vivo, intraocular pressure (IOP) elevation was carried out in one eye of retired breeder Brown Norway rats. Two weeks following IOP elevation, retina sections from IOP-elevated eyes and contralateral eyes were analyzed for expression of LC3B and TOM20.

Results : ET-1 treatment of primary RGCs for 24 h produced a decrease in co-localization of LC3B and TOM20. A decreased co-localization of MitoTracker and LysoTracker was also found in primary RGCs treated with ET-1, indicative of decreased mitophagy. IOP elevation for 2 weeks in rats, produced a significant decrease in colocalization of LC3B and TOM20 (n=4, p<0.05) in retinal ganglion cell layer.

Conclusions : A decreased colocalization of TOM20 with LC3B during ET-1 treatment as well as during IOP elevation could be indicative of ET-1 mediated decrease in mitophagy in RGCs. A decline in mitophagy could be one of the mechanisms by which ET-1 promotes neurodegeneration of RGCs in glaucoma.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

×
×

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.

×