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

  • Int J Mol Sci. 2019 Sep 27;20(19):4807. doi: 10.3390/ijms20194807.
Feng Su  1 ,  Christine Spee  2 ,  Eduardo Araujo  3 ,  Eric Barron  4 ,  Mo Wang  5 ,  Caleb Ghione  6 ,  David R Hinton  7  8 ,  Steven Nusinowitz  9 ,  Ram Kannan  10  11 ,  Srinivasa T Reddy  12  13  14 ,  Robin Farias-Eisner  15  16
Affiliations
  • 1. Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. [email protected].
  • 2. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. [email protected].
  • 3. Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA. [email protected].
  • 4. The Stephen J. Ryan Initiative for Macular Research, Doheny Eye Institute, Los Angeles, CA 90033, USA. [email protected].
  • 5. The Stephen J. Ryan Initiative for Macular Research, Doheny Eye Institute, Los Angeles, CA 90033, USA. [email protected].
  • 6. Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA. [email protected].
  • 7. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. [email protected].
  • 8. Department of Ophthalmology, University of Southern California, Los Angeles, CA 90033, USA. [email protected].
  • 9. Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA. [email protected].
  • 10. Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA. [email protected].
  • 11. The Stephen J. Ryan Initiative for Macular Research, Doheny Eye Institute, Los Angeles, CA 90033, USA. [email protected].
  • 12. Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. [email protected].
  • 13. Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. [email protected].
  • 14. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. [email protected].
  • 15. Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. [email protected].
  • 16. Department of Obstetrics and Gynecology, School of Medicine, Creighton University, Omaha, NE 68178, USA. [email protected].
PMID: 31569695 DOI: 10.3390/ijms20194807
Abstract

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.

Keywords
HDL-mimetic peptide; OCT; apoptosis; geographic atrophy; retinal function; retinal pigment epithelium (RPE); retinitis pigmentosa; sodium iodate.
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