01/01/2020 → 31/12/2021
Dr Isabel Lopez Sanchez
Centre for Eye Research Australia and Department of Surgery, Ophthalmology, University of Melbourne
Identifying pathogenic and protective pathways from blindness in a human retinal model of Leber’s hereditary optic neuropathy
Mitochondria generate most of the energy required by cells. The human retina is one of the most energy-demanding tissues in the body and vision loss is a common feature of mitochondrial
diseases. Existing treatments are limited, and carriers of mitochondrial genetic mutations remain at risk of blindness for life. In this project, I will determine the mechanisms that help prevent vision loss in Leber’s hereditary optic neuropathy (LHON), a common primary mitochondrial disease. LHON’s well-defined features make it an ideal model in which to identify protective pathways from mitochondrial dysfunction. However, the lack of a human-relevant research model is a major obstacle for developing efficient treatments that benefit patients.
Here, I will generate an induced pluripotent stem cell-derived human retinal model of LHON. Using this model, I will identify retinal-specific protective pathways present in asymptomatic LHON carriers. Finally, I will investigate the biomarker potential of identified targets in tissues from living patients and in post-mortem human LHON eye tissue. Knowledge generated from this project will transform our understanding of the mechanisms underpinning LHON pathology, by identifying protective targets in the target organ of the disease for the first time.