Mitochondrial Mechanisms in Optic Neuropathy

University Of California Davis, Davis CA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Our long-term objective is to clarify the mitochondrial pathogenetic mechanisms of both Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), which eventually causes optic neurodegeneration as a result of two distinct mitochondrial causes, defects in which may be integrated into a common pathophysiological pathway. Our microarray analyses have supported an alternative mechanism for LHON, and thus our Aims have been focused in that direction. Firstly, we propose to confirm the altered expression of 'gene leads' by RT-PCR and Western and Elisa, and to assay the effects of LHON mutations on secretion and cell migration in LHON and DOA cell models. Secondly we will test alterations in Complex 1, and of mitochondrial structure. Thirdly, we will dissect the source of altered mitochondrial Ca 2+ signaling in LHON models. Fourthly, we will attempt to create new cellular LHON models to strongly test the hypotheses, and to test possible homologies between LHON and DOA by microarray. Lastly, we will begin to test mechanism-based compounds, and to also begin random screening of compounds, for anti-LHON and anti-DOA effects.