June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
SS-31 ameliorates age-induced visual decline and cone-mediated retinal dysfunction.
Author Affiliations & Notes
  • Nazia Alam
    Burke Neurological Institute, White Plains, New York, United States
    Physiology and Biophysics, Weill Cornell Medicine, New York, New York, United States
  • Kristine Tsantilas
    Biochemistry, UW School of Medicine, Seattle, New York, United States
  • Whitney M. Cleghorn
    Biochemistry, UW School of Medicine, Seattle, New York, United States
    Ophthalmology, UW School of Medicine, Seattle, New York, United States
  • Austin M. Rountree
    UW Diabetes Institute, Seattle, Washington, United States
  • Celia Bisbach
    Biochemistry, UW School of Medicine, Seattle, New York, United States
  • Brian Robbings
    Biochemistry, UW School of Medicine, Seattle, New York, United States
    UW Diabetes Institute, Seattle, Washington, United States
  • Martin Sadilek
    Chemistry, UW School of Medicine, Seattle, Washington, United States
  • Ian R. Sweet
    UW Diabetes Institute, Seattle, Washington, United States
  • Jim Hurley
    Biochemistry, UW School of Medicine, Seattle, New York, United States
    Ophthalmology, UW School of Medicine, Seattle, New York, United States
  • Glen Prusky
    Burke Neurological Institute, White Plains, New York, United States
    Physiology and Biophysics, Weill Cornell Medicine, New York, New York, United States
  • Footnotes
    Commercial Relationships   Nazia Alam, CerebralMechanics Inc. (E); Kristine Tsantilas, None; Whitney Cleghorn, None; Austin Rountree, None; Celia Bisbach, None; Brian Robbings, None; Martin Sadilek, None; Ian Sweet, None; Jim Hurley, None; Glen Prusky, CerebralMechanics Inc (P)
  • Footnotes
    Support  NIA 2P01AG001751-33A1
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4279. doi:
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      Nazia Alam, Kristine Tsantilas, Whitney M. Cleghorn, Austin M. Rountree, Celia Bisbach, Brian Robbings, Martin Sadilek, Ian R. Sweet, Jim Hurley, Glen Prusky; SS-31 ameliorates age-induced visual decline and cone-mediated retinal dysfunction.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4279.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Age-related visual decline and retinal disease make a large contribution to disability and have resisted effective treatment. In light of evidence that mitochondrial function declines in the visual system with age, we investigated in mice whether a therapeutic intervention thought to improve mitochondrial function can prevent or treat age-related visual and retinal dysfunction.

Methods : Spatial visual function of C57Bl/6 mice in photopic and scotopic lighting conditions was measured over the adult lifespan using a virtual optokinetic system. SS-31, a peptide that targets the inner mitochondrial membrane was administered (1-3mg/kg) at different ages and for varying lengths of time. The drug was administered via single or daily injections, or eye drops, or minipumps. To identify the physiological basis of behavioral changes, electroretinogram measures were made prior to euthanasia, and metabolic flux and O2 consumption measures were made in retinas and eyecups ex vivo.

Results : Impaired photopic acuity emerged near 18 months, and declined ~60% by 34 months. Daily application of SS-31 initiated at 18 months mitigated subsequent visual decline. When initiated at 24 months, an age when spatial frequency thresholds were reduced by about 16%, daily SS-31 returned photopic function to adult norms within 2 months. Recovered function persisted for at least 3 months after treatment was withdrawn. A single treatment at 24 months also delayed subsequent visual decline. The effect of daily application from 32 months was less efficacious, but still enabled improvement within 2 months. The effects of age and treatment on contrast sensitivity was similar to those on acuity, and systemic and eye drop applications of SS-31 had comparable effects. Scotopic spatial visual function was largely unaffected by age or treatment. Altered function was independent of variation in optical clarity. Metabolic flux from 13C glucose through glycolysis and into mitochondria and O2 consumption were unaffected by SS-31 treatment. The dominant source of retinal change appears to be mediated through cone circuitry, which was confirmed with flicker fusion ERGs that show an improvement in the critical flicker fusion frequency after SS-31 treatment.

Conclusions : SS-31 treatment adaptively alters the aging visual system, which provides a rationale to investigate its use to treat pathophysiologies of human visual aging and age-related visual disease.

This is a 2020 ARVO Annual Meeting abstract.

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