A Novel HDL-Mimetic Peptide HM-10/10 Protects RPE and Photoreceptors in Murine Models of Retinal Degeneration.
Feng SuChristine SpeeEduardo AraujoEric BarronMo WangCaleb GhioneDavid R HintonSteven NusinowitzRam KannanSrinivasa T ReddyRobin Farias-EisnerPublished in: International journal of molecular sciences (2019)
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.
Keyphrases
- cell death
- age related macular degeneration
- diabetic retinopathy
- optical coherence tomography
- oxidative stress
- high density
- optic nerve
- endothelial cells
- type diabetes
- stem cells
- diabetic rats
- cell proliferation
- mass spectrometry
- mesenchymal stem cells
- cell therapy
- adipose tissue
- high glucose
- pi k akt
- skeletal muscle
- atomic force microscopy