July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Nucleoside reverse transcriptase inhibitors (NRTI) prevent inflammasome activation in retinal pigmented epithelium cells.
Author Affiliations & Notes
  • DAIPAYAN BANERJEE
    Opthalmology, UNIVERSITY OF VIRGINIA, Charlottesville, Virginia, United States
  • Junichi Fukuhara
    University of Kentucky, Lexington, Kentucky, United States
  • Dongxu Fu
    Opthalmology, UNIVERSITY OF VIRGINIA, Charlottesville, Virginia, United States
  • Shinichi Fukuda
    Opthalmology, UNIVERSITY OF VIRGINIA, Charlottesville, Virginia, United States
  • Shuichiro Hirahara
    Opthalmology, UNIVERSITY OF VIRGINIA, Charlottesville, Virginia, United States
  • Younghee Kim
    University of Kentucky, Lexington, Kentucky, United States
  • Benjamin J Fowler
    University of Kentucky, Lexington, Kentucky, United States
  • Tetsuhiro Yasuma
    University of Kentucky, Lexington, Kentucky, United States
  • Reo Yasuma
    University of Kentucky, Lexington, Kentucky, United States
  • Kameshwari Ambati
    Opthalmology, UNIVERSITY OF VIRGINIA, Charlottesville, Virginia, United States
  • Nagaraj Kerur
    Opthalmology, UNIVERSITY OF VIRGINIA, Charlottesville, Virginia, United States
  • Bradley Gelfand
    Opthalmology, UNIVERSITY OF VIRGINIA, Charlottesville, Virginia, United States
  • Jayakrishna Ambati
    Opthalmology, UNIVERSITY OF VIRGINIA, Charlottesville, Virginia, United States
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2475. doi:
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      DAIPAYAN BANERJEE, Junichi Fukuhara, Dongxu Fu, Shinichi Fukuda, Shuichiro Hirahara, Younghee Kim, Benjamin J Fowler, Tetsuhiro Yasuma, Reo Yasuma, Kameshwari Ambati, Nagaraj Kerur, Bradley Gelfand, Jayakrishna Ambati; Nucleoside reverse transcriptase inhibitors (NRTI) prevent inflammasome activation in retinal pigmented epithelium cells.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2475.

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

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Abstract

Purpose : Geographic atrophy (GA), the untreatable form of age-related macular degeneration (AMD), the leading cause of legal blindness in aged populations globally, is characterized by loss of retinal pigmented epithelium layer (RPE). DICER1-deficit driven Alu RNA accumulation induces NLRP3 inflammasome activation, leading to RPE cell death. The purpose of this study is to investigate the efficacy of NRTIs as novel therapies for GA by blocking inflammasome activation induced by various AMD-relevant RPE stressors.

Methods : Primary human RPE cells in culture were exposed to various AMD-relevant RPE stressors namely, drusen component amyloid-beta 1-40, iron overload (Fe3+ ammonium citrate), cigarette smoke extract (CSE), oxidative stress inducer paraquat, double-stranded RNA Poly I:C, and sodium iodate. Cells were pre-treated with NRTIs and added again following replacement of Penicillin/Streptomycin-containing media. Inflammasome activation was monitored by immunoblotting for caspase-1 and ELISA for secreted IL-18 and IL-1B. Cell viability was monitored by MTS assay.

Results : NRTI treatment inhibited inflammasome activation (as monitored by caspase-1 immunoblotting and ELISA for IL-18 and IL-1B) induced by amyloid beta 1-40, iron-overload, cigarette smoke extract, paraquat, Poly I:C, and sodium iodate. NRTI treatment also suppressed Paraquat-induced inhibition of ARPE19 cell proliferation.

Conclusions : Our findings reveal that NRTIs attenuate inflammasome activation by six different AMD-relevant RPE stressors. Thus NRTIs are potentially promising novel therapeutic candidates for the presently incurable menace of GA.

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

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