2. Academic Validation
  3. A Novel HDL-Mimetic Peptide HM-10/10 Protects RPE and Photoreceptors in Murine Models of Retinal Degeneration

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

Affiliations

  • 1 Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. fsu@mednet.ucla.edu.
  • 2 Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. ChristineK.Spee@med.usc.edu.
  • 3 Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA. araujo@jsei.ucla.edu.
  • 4 The Stephen J. Ryan Initiative for Macular Research, Doheny Eye Institute, Los Angeles, CA 90033, USA. ebarron2@doheny.org.
  • 5 The Stephen J. Ryan Initiative for Macular Research, Doheny Eye Institute, Los Angeles, CA 90033, USA. mwang@doheny.org.
  • 6 Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA. CGhion@hotmail.com.
  • 7 Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. dhinton@usc.edu.
  • 8 Department of Ophthalmology, University of Southern California, Los Angeles, CA 90033, USA. dhinton@usc.edu.
  • 9 Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA. nusinowitz@jsei.ucla.edu.
  • 10 Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA. rkannan@doheny.org.
  • 11 The Stephen J. Ryan Initiative for Macular Research, Doheny Eye Institute, Los Angeles, CA 90033, USA. rkannan@doheny.org.
  • 12 Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. sreddy@mednet.ucla.edu.
  • 13 Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. sreddy@mednet.ucla.edu.
  • 14 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. sreddy@mednet.ucla.edu.
  • 15 Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. robinFarias-Eisner@creighton.edu.
  • 16 Department of Obstetrics and Gynecology, School of Medicine, Creighton University, Omaha, NE 68178, USA. robinFarias-Eisner@creighton.edu.
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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