June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Subretinal Lipid Hydroperoxide Induced-Oxidative Stress and Retinal Degeneration Results in a Rat Model of Age-Related Macular Degeneration
Author Affiliations & Notes
  • Soo-Young Kim
    Center for Nanomedicine, Opthalamology , Wilmer Eye Institute, Johns Hopkins Univ, Baltimore, Maryland, United States
  • Siva Pramodh Kambhampati
    Center for Nanomedicine, Opthalamology , Wilmer Eye Institute, Johns Hopkins Univ, Baltimore, Maryland, United States
  • Imran Ahmed Bhutto
    Center for Nanomedicine, Opthalamology , Wilmer Eye Institute, Johns Hopkins Univ, Baltimore, Maryland, United States
  • Gerard A Lutty
    Center for Nanomedicine, Opthalamology , Wilmer Eye Institute, Johns Hopkins Univ, Baltimore, Maryland, United States
  • Kannan Rangaramanujam
    Center for Nanomedicine, Opthalamology , Wilmer Eye Institute, Johns Hopkins Univ, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Soo-Young Kim, None; Siva Pramodh Kambhampati, None; Imran Bhutto, None; Gerard Lutty, None; Kannan Rangaramanujam, Orpheris (I)
  • Footnotes
    Support  NEI EY025304-01, Altsheler Durell Grant and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2306. doi:
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    • Get Citation

      Soo-Young Kim, Siva Pramodh Kambhampati, Imran Ahmed Bhutto, Gerard A Lutty, Kannan Rangaramanujam; Subretinal Lipid Hydroperoxide Induced-Oxidative Stress and Retinal Degeneration Results in a Rat Model of Age-Related Macular Degeneration
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):2306.

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

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Abstract

Purpose : In the pathogenesis of AMD, chronic oxidative stress and inflammation have been shown to be key events in early AMD, leading to degeneration and angiogenesis (CNV) in later stages. We have previously reported that subretinal injection of lipid hydroperoxide, 13(S)-hydroperoxy-9Z, 11E-octadecadienoic acid (HpODE) causes inflammation and CNV but the retinal oxidative stress and degeneration has not been explored. In this study, we investigate the involvement of oxidative stress and retinal degeneration in disease progression.

Methods : HpODE was administered via subretinal injection in Sprague Dawley rats on day 0 and the time course of oxidative stress and retinal degeneration was studied qualitatively using immunohistochemistry (flatmount and crossections), and quantitatively via qPCR and western blot on day 2, 5 12 and 20.

Results : Subretinal lipid provoked oxidative stress and damage in retinal tissue and retinal pigment epithelium (RPE) with accumulated autofluoresent material in subretina. RPE degeneration and atrophy was detected early at day 5 followed by neural tissue degeneration at day 12 with robust TUNEL positive cells. Oxidative stress marker, 8-OHdG, was demonstrated in RPE cells at day 2 and oxidative damage (4-HNE, MDA, NT and 8-OHdG) increased in retinal tissue from day 5 to 12. Retinal inflammation was confirmed by subretinal microglial/macrophage accumulation and Müller glial activation in the lipid injected area was present at day 5. Western blot and RT-qPCR confirmed an increase of pro-apoptotic Bax. We further confirmed an increase in NLRP3 inflammasome and pro-inflammatory cytokine TNFa and a decrease of anti-oxidative Nrf2, Sod1 and Sod2 in RPE/Choroid tissue.

Conclusions : Understanding the roles of oxidative stress and inflammation in AMD progression may give insights for developing targeted therapies for early and intermediate stages of AMD. This model is a relevant experimental model for nonexudative (dry) AMD as well with the previously report as an exudative (wet) AMD, and would be useful to study molecular pathology of oxidative damage in retina diseases and protective effect of antioxidant and anti-inflammatory substances.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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