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:10.3390/ijms20194807

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.

Authors

Feng Su¹, Christine Spee², Eduardo Araujo³, Eric Barron⁴, Mo Wang⁵, Caleb Ghione⁶, David R Hinton^{7

8}, Steven Nusinowitz⁹, 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. 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.

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.

MeSH terms

Animals
Apoptosis
Caspase 3 / metabolism
Caspase 7 / metabolism
Disease Models, Animal
Iodates
Lipoproteins, HDL / metabolism*
Mice
Oxidative Stress / drug effects
Peptides / pharmacology*
Photoreceptor Cells / drug effects*
Photoreceptor Cells / metabolism*
Retinal Degeneration / diagnosis
Retinal Degeneration / etiology
Retinal Degeneration / metabolism*
Retinal Pigment Epithelium / metabolism*
Retinal Pigment Epithelium / pathology
Tomography, Optical Coherence

Substances

Iodates
Lipoproteins, HDL
Peptides
Caspase 3
Caspase 7
sodium iodate

Grants and funding

FN# 49178/Annenberg Foundation