Loss of functional OPA1 unbalances redox state: implications in dominant optic atrophy pathogenesis.

ABSTRACT:

Objective

OPA1 mutations cause protein haploinsufficiency leading to dominant optic atrophy (DOA), an incurable retinopathy with variable severity. Up to 20% of patients also develop extraocular neurological complications. The mechanisms that cause this optic atrophy or its syndromic forms are still unknown. After identifying oxidative stress in a mouse model of the pathology, we sought to determine the consequences of OPA1 dysfunction on redox homeostasis.

Methods

Mitochondrial respiration, reactive oxygen species levels, antioxidant defenses, and cell death were characterized by biochemical and in situ approaches in both in vitro and in vivo models of OPA1 haploinsufficiency.

Results

A decrease in aconitase activity suggesting an increase in reactive oxygene species

SUBMITTER: Millet AM 

PROVIDER: S-EPMC4891995 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature