International Journal of Molecular Sciences (Sep 2019)

A Novel HDL-Mimetic Peptide HM-10/10 Protects RPE and Photoreceptors in Murine Models of Retinal Degeneration

  • Feng Su,
  • Christine Spee,
  • Eduardo Araujo,
  • Eric Barron,
  • Mo Wang,
  • Caleb Ghione,
  • David R. Hinton,
  • Steven Nusinowitz,
  • Ram Kannan,
  • Srinivasa T. Reddy,
  • Robin Farias-Eisner

DOI
https://doi.org/10.3390/ijms20194807
Journal volume & issue
Vol. 20, no. 19
p. 4807

Abstract

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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 generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO3), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. 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.

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