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Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration

Sonali Nashine1, Pinchas Cohen2, Anthony B Nesburn1,3

  • 1Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, USA.

Scientific Reports
|October 13, 2018
PubMed

Insights

Small humanin-like peptide 2 (SHLP2), a mitochondrial-derived peptide, protects against age-related macular degeneration (AMD) by restoring mitochondrial function and preventing cell death. This peptide shows therapeutic potential for AMD treatment.

Area of Science:

  • Mitochondrial biology
  • Neurodegenerative diseases
  • Ophthalmology

Background:

  • Mitochondrial-derived peptides (MDPs) are emerging therapeutic targets for neurodegenerative diseases.
  • SHLP2 is a novel MDP encoded by the MT-RNR2 gene in mitochondrial DNA (mtDNA).
  • Age-related macular degeneration (AMD) is a leading cause of blindness associated with mitochondrial dysfunction.

Purpose of the Study:

  • To investigate the protective effects of exogenously-added SHLP2 in an in vitro human ARPE-19 cell model of AMD.
  • To determine if SHLP2 can counteract mitochondrial toxicity and oxidative stress observed in AMD cells.

Main Methods:

  • Utilized an in vitro human transmitochondrial ARPE-19 cell model of AMD.
  • Assessed the impact of SHLP2 treatment on oxidative phosphorylation (OXPHOS) complex protein subunits, cell viability, mitochondrial integrity, mtDNA copy number, and apoptosis.
  • Evaluated SHLP2's efficacy in attenuating amyloid-β-induced toxicity.

Main Results:

  • AMD cells exhibited down-regulated MT-RNR2 and reduced OXPHOS complex protein subunits, indicating mitochondrial toxicity.
  • SHLP2 treatment restored OXPHOS protein levels, preserved cell and mitochondrial viability, and increased mtDNA copy number.
  • SHLP2 demonstrated anti-apoptotic effects and attenuated amyloid-β-induced cellular and mitochondrial damage in AMD cells.

Conclusions:

  • SHLP2 plays a significant protective role in an in vitro model of AMD.
  • This study supports the therapeutic potential of SHLP2 for treating age-related macular degeneration.
  • SHLP2 represents a promising novel therapeutic strategy for AMD, a major cause of age-related vision loss.

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