Extending the Optic atrophy 1 dependent cristae remodeling: from models to a therapy of autosomal dominant optic atrophy

Dominant optic atrophy (ADOA) is a genetic disease characterized by progressive loss of sight, starting during early childhood. This is caused by the death of the retinal ganglion cells, the neurons transmitting the images from the eye to the brain. This death is painless and occurs at a steady pace over the years, ultimately leading to blindness. If we want to generate new drugs that block this degeneration, we need to understand the processes that lead to the loss of these cells. Mitochondria, the “powerhouse” of the cells, are not only responsible for generating the energy that our cells need to live, but are also key players in the intricate networks of cellular signals. Some proteins, called dynamins, control the shape of mitochondria and when they are damaged serious diseases ensue. In particular, one of these proteins, called Opa1, is affected in dominant optic atrophy. We intend to study how this protein is regulated, to elucidate the signals that the mitochondria carrying mutated Opa1 release, to explore if drugs that interfere with these signals can stop the path to blindness in a mouse model of ADOA. If successful, our project will bring to the preclinical stage a potential therapy for a currently untreatable disease.