Description:

“Mitochondrial Disorders of the Retina: Insights from Multiomic Studies of the Human Eyes”

Robert Mullins, MS, PhD

Carver College of Medicine

Professor of Ophthalmology and Visual Sciences

University of Iowa, Iowa City 

Abstract 
Mitochondria are maternally inherited critical organelles that possess their own genomes. Some variants within the mitochondrial genome, including an A to G transition at position 3243 (3243A>G), disrupt organelle function and can lead to mild to severe multi-system disease. Unlike mutations in the nuclear genome, mitochondrial mutations can be unevenly distributed across mitochondria, cells, tissues, and organs in a phenomenon called heteroplasmy. Studying eyes and cells from unaffected individuals and a donor with the 3243A>G-associated disease referred to as mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), we profiled gene expression, chromatin accessibility state, and heteroplasmy at the single cell level from the retina and choroid. Surprisingly, heteroplasmy is uneven across different cells in the eye, with high and low proportions of mutant mitochondrial genomes in different cell types, including cell types from the same embryonic sources. These findings demonstrate a non-random nature of mitochondrial variant distribution and provides new insights into mitochondrial disease.