Nickells Lab
Department of Ophthalmology and Visual Sciences

Mitochondrial Dynamics

Mitochondrial Dynamics in Retinal Ganglion Cells

Mitochondrial health plays a huge role in the resilience of neurons to damaging conditions and retinal ganglion cells are no exception. In fact, ganglion cells may be the most susceptible cells if the mitochondria are functioning at less than optimal capacity. This is evident in individuals who carry mutations in genes that affect mitochondrial dynamics and function. Even though every mitochondria in every cell is affected, the principal disease manifestation from these kinds of mutations can be a spontaneous optic neuropathy. We are interested in fully characterizing the mitochondrial population in ganglion cells, including understanding their normal morphology and function in different compartments of retinal ganglion cells, both before and after damage to the optic nerve.

Images of Mitochondria. Four slides showing the progression/evulsion of dendritic arbors of ganglion cells. Black background. Gray dendritic structure with sporadic splotches of red and bright green.
A series of 4 images showing evulsions linked to the processes of the dendritic arbors of ganglion cells in Tg-Thy1-mitoCFP transgenic mice. The mitoCFPtransgene selectively labels the mitochondria in the retinal ganglion cells and can be used to map both shape and size of these organelles when imaged in 3 dimensions using confocal microscopy. Each set of 2 panels shows a surface rendering of the arbor evulsions (grey) and the presence of 1-2 large mitochondria within each evulsion. We think these evulsions are being engulfed by adjacent microglia in a process of mitochondrial turnover called transmitophagy.

 

Selected Reading

  1. Maes ME, Grosser JA, Fehrman RL, Schlamp CL, Nickells RW. Completion of BAX recruitment correlates with mitochondrial fission during apoptosis. Sci. Rep. 9:16565, 2019.
  2. Grosser JA, Fehrman RL, Keefe D, Redmon M, Nickells RW. The effects of a mitochondrial targeted peptide (elamipretide/SS31) on BAX recruitment and activation during apoptosis. BMC Res. Notes. 14:198, 2021.
  3. Muench NA, Patel S, Maes ME, Donahue RJ, Ikeda A, Nickells RW. The influence of mitochondrial dynamics and function on retinal ganglion cell susceptibility in optic nerve disease.Cells. 10:1593, 2021.