Premium
Reenergizing aged mitochondria to combat retinal degeneration (LB555)
Author(s) -
Mills William,
Alam Nazia,
Prusky Glen,
Szeto Hazel
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb555
Subject(s) - macular degeneration , choroid , retinal pigment epithelium , retinal degeneration , diabetic retinopathy , medicine , mitochondrion , inflammation , retina , retinal , ophthalmology , diabetes mellitus , biology , endocrinology , microbiology and biotechnology , neuroscience
Bioenergetic failure is the major risk factor for Age‐Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR). Within the eye, the delicate microvasculature of the choroid and the metabolically active retinal pigment epithelium (RPE) are especially sensitive to the stresses of age and diabetes. Using mouse models of diabetes and advanced age, we demonstrated diabetes/aging‐induced abnormalities of the mitochondria in the choroid and RPE, alterations to the choroidal microvasculature, disruption to the RPE, and an increase in inflammation markers. Treatment with the novel cardiolipin‐targeted antioxidant tetrapeptide SS‐31, after onset of diabetes or in aged mice, restored proper RPE integrity and mitochondrial morphology, as well as reduced the intrusion of neovascular tufts from the choroid through the RPE and the level of inflammation markers. Moreover, SS‐31 administration restored visual function as demonstrated by optokinetic tracking. Thus we are the first to pioneer a mitochondrial‐targeted approach for resolving feed‐forward mitochondrial damage and restoring bioenergetic capacity in the choroid and RPE, thereby preventing disease progression and restoring visual function in early AMD and DR. Grant Funding Source : Supported by the Tri‐Institutional Training Program in Vision Research (5T32EY007138‐20)