June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Protective action of a novel HDL mimetic peptide, HM-10/10 in RPE in vitro and in a murine model of sodium iodate induced retinal degeneration
Author Affiliations & Notes
  • Ram Kannan
    Ophthalmology, Doheny Eye Institute, Los Angeles, California, United States
  • Feng Su
    Obstetrics and Gynecology, University of California, Los Angeles, California, United States
  • Robin Farias-Eisner
    Obstetrics and Gynecology, University of California, Los Angeles, California, United States
  • Christine Spee
    Pathology, University of Southern California, Los Angeles, California, United States
  • Eric Barron
    Ophthalmology, Doheny Eye Institute, Los Angeles, California, United States
  • David R Hinton
    Pathology, University of Southern California, Los Angeles, California, United States
    Ophthalmology, University of Southern California, Los Angeles, California, United States
  • Srinivasa T Reddy
    Medicine, University of California, Los Angeles, California, United States
    Molecular and Medical Pharmacology, University of California, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Ram Kannan, None; Feng Su, None; Robin Farias-Eisner, Salvaregen (I); Christine Spee, None; Eric Barron, None; David Hinton, None; Srinivasa Reddy, Salvaregen (I)
  • Footnotes
    Support  EY01545, Arnold and Mabel Beckman Foundation, Carl and Roberta Deutsch Family Foundation, HL-71776
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5364. doi:
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    • Get Citation

      Ram Kannan, Feng Su, Robin Farias-Eisner, Christine Spee, Eric Barron, David R Hinton, Srinivasa T Reddy; Protective action of a novel HDL mimetic peptide, HM-10/10 in RPE in vitro and in a murine model of sodium iodate induced retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5364.

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

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Abstract

Purpose : Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We developed a chimeric high density lipoprotein (HDL) - mimetic peptide (HM-10/10) that not only reduces oxidative stress but also prevents oxidative stress-induced cell death in cell culture models. The purpose of this study was to investigate the effect of HM-10/10 in the regulation of human RPE cell death from oxidative and sodium iodate (NaIO3) and to determine the effect of HM-10/10 in a model of NaIO3-induced retinal degeneration.

Methods : Early passage (2-4) primary cultured human RPE cells were treated with 200 uM tBH or NaIO3 (200 µg/ml or 500 µg/ml) for 24 h with or without the co-treatment of HM-10/10 (10 µg/ml). Apoptotic cell death was measured using TUNEL assay and caspase-3 by western blot. Twelve C57Bl6/J male mice were divided into three groups of four mice per group and treated as follows: control mice (PBS-treated), NaIO3-treated (20 mg/kg) mice, and NaIO3-treated (20 mg/kg) mice with HM-10/10 (100 mg/kg) added to their chow. At the end of three weeks, eyes were enucleated, and frozen sections of retinal tissue were used for histology. Retinal sections were scanned and retinal thickness was quantified (Aperial Scan Scope, Leica Biosystems).

Results : HM-10/10 (10 µg/ml) significantly inhibited RPE cell death from 24h tBH treatment (p<0.01 vs tBH-treated). Incubation of RPE with either 200 µg/ml or 500 µg/ml of NaIO3 resulted in increased TUNEL-positive cells and co-treatment with HM-10/10 (10 µg/ml) at either NaIO3 concentration significantly reduced apoptotic cell death. Caspase-3 activation was significantly elevated in RPE cells treated with 200 µM H2O2 or NaIO3 alone, whereas co-treatment with HM-10/10 inhibited activation of caspase-3. In mice, intravenous NaIO3 caused a decrease in retinal thickness vs PBS controls and HM-10/10 in the diet significantly (p<0.05 vs NaIO3-treated) restored retinal thickness to control values.

Conclusions : Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration.

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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