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Reenergizing aged mitochondria to combat retinal degeneration (1060.1)
Author(s) -
Mills William,
Alam Nazia,
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.1060.1
Subject(s) - lipofuscin , mitochondrion , oxidative stress , bioenergetics , retinal pigment epithelium , retinal degeneration , macular degeneration , microbiology and biotechnology , antioxidant , retinal , oxidative phosphorylation , chemistry , biology , biochemistry , medicine , ophthalmology
The major risk factors for Age‐Related Macular Degeneration (AMD) are age and oxidative stress. Aging is associated with bioenergetic failure, especially of the metabolically active retinal pigment epithelium (RPE), which is required for phagocytic function of photoreceptor outer segments. A2E and lipid peroxides in lipofuscin can increase the feed‐forward loop of oxidative damage to mitochondria in the RPE. Here, we propose a novel approach for resolving feed‐forward mitochondrial damage with the mitochondria‐targeted peptide SS‐31. With its strong antioxidant properties and ability to promote electron transport in aging mitochondria, we show optimization of ATP synthesis and minimization of oxidative stress. We created an age‐relevant RPE model using complex I inhibitors and A2E or lipid peroxide (tBHP) and demonstrated relevant energetic failure. SS‐31 treatment restored ATP synthesis, antioxidant capacity and phagocytic function of the RPE. Moreover, SS‐31 treatment in aged mice and rats improved visual acuity as measured by optokinetic tracking. Thus, our novel mitochondria‐targeted approach will preserve RPE mitochondrial function and will potentially prevent or delay progression of early AMD.