Abstract |
One feature common to many of the pathways implicated in retinal degeneration is increased metabolic stress leading to impaired mitochondrial function. We found that exposure of cells to calcium ionophores or oxidants as metabolic stressors diminish maximal mitochondrial capacity. A library of 50,000 structurally diverse "drug-like" molecules was screened for protection against loss of calcium-induced loss of mitochondrial capacity in 661W rod-derived cells and C6 glioblastomas. Initial protective hits were then tested for protection against IBMX-induced loss of mitochondrial capacity as measured via respirometry. Molecules that protected mitochondria were then evaluated for protection of rod photoreceptor cells in retinal explants from rd1 mice. Two of the molecules attenuated loss of photoreceptor cells in the rd1 model. In the 661W cells, exposure to calcium ionophore or tert-butylhydroperoxide caused mitochondrial fragmentation that was blocked with the both compounds. Our studies have identified molecules that protect mitochondria and attenuate loss of photoreceptors in models of retinal degeneration suggesting that they could be good leads for development of therapeutic drugs for treatment of a wide variety of retinal dystrophies.
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Authors | Craig Beeson, Chris Lindsey, Cecile Nasarre, Mausumi Bandyopadhyay, Nathan Perron, Bärbel Rohrer |
Journal | Advances in experimental medicine and biology
(Adv Exp Med Biol)
Vol. 854
Pg. 449-54
( 2016)
ISSN: 0065-2598 [Print] United States |
PMID | 26427445
(Publication Type: Journal Article)
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Chemical References |
- Protective Agents
- Small Molecule Libraries
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Topics |
- Animals
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Disease Models, Animal
- Glycolysis
(drug effects)
- Mice, Mutant Strains
- Mitochondria
(drug effects, metabolism)
- Organ Culture Techniques
- Photoreceptor Cells, Vertebrate
(drug effects, metabolism)
- Protective Agents
(pharmacology)
- Retina
(drug effects, metabolism, pathology)
- Retinitis Pigmentosa
(genetics, metabolism, prevention & control)
- Small Molecule Libraries
(pharmacology)
- Stress, Physiological
(drug effects)
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