| First Author | Gospe SM 3rd | Year | 2019 |
| Journal | J Biol Chem | Volume | 294 |
| Issue | 33 | Pages | 12432-12443 |
| PubMed ID | 31248988 | Mgi Jnum | J:281143 |
| Mgi Id | MGI:6369133 | Doi | 10.1074/jbc.RA119.007945 |
| Citation | Gospe SM 3rd, et al. (2019) Photoreceptors in a mouse model of Leigh syndrome are capable of normal light-evoked signaling. J Biol Chem 294(33):12432-12443 |
| abstractText | Mitochondrial dysfunction is an important cause of heritable vision loss. Mutations affecting mitochondrial bioenergetics may lead to isolated vision loss or life-threatening systemic disease, depending on a mutation's severity. Primary optic nerve atrophy resulting from death of retinal ganglion cells is the most prominent ocular manifestation of mitochondrial disease. However, dysfunction of other retinal cell types has also been described, sometimes leading to a loss of photoreceptors and retinal pigment epithelium that manifests clinically as pigmentary retinopathy. A popular mouse model of mitochondrial disease that lacks NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4), a subunit of mitochondrial complex I, phenocopies many traits of the human disease Leigh syndrome, including the development of optic atrophy. It has also been reported that ndufs4 (-/-) mice display diminished light responses at the level of photoreceptors or bipolar cells. By conducting electroretinography (ERG) recordings in live ndufs4 (-/-) mice, we now demonstrate that this defect occurs at the level of retinal photoreceptors. We found that this deficit does not arise from retinal developmental anomalies, photoreceptor degeneration, or impaired regeneration of visual pigment. Strikingly, the impairment of ndufs4 (-/-) photoreceptor function was not observed in ex vivo ERG recordings from isolated retinas, indicating that photoreceptors with complex I deficiency are intrinsically capable of normal signaling. The difference in electrophysiological phenotypes in vivo and ex vivo suggests that the energy deprivation associated with severe mitochondrial impairment in the outer retina renders ndufs4 (-/-) photoreceptors unable to maintain the homeostatic conditions required to operate at their normal capacity. |
