Deciphering the Local Role of Mitochondria in Glaucoma

We will study how mitochondria are affected by glaucomatous stress depending on their cellular location. Aim 1: Are mitochondria from retinal ganglion cells (RGCs) axons and soma (cell body) regulated the same way? Aim 2: How these local regulations are affected under glaucomatous stress?

Mitochondria, an intracellular organelle responsible for key cellular processes such as energy production and programmed cell death regulation, have been shown to be impaired in retinal ganglion cells (RGCs) affected by glaucoma. RGCs have an extreme architecture with axons extending from the retina in the eye all the way to the brain via the optic nerve. This complex cellular morphology creates the need for mitochondria to tailor their functions to the specific demands of very different cellular compartments such as the axon in the optic nerve and the soma in the retina. Because an early event in glaucoma pathophysiology is a focal insult to RGC axons we propose to investigate the role and regulation of local mitochondrial functions specifically in RGC axons and somas in both healthy and conditions known to be risks factors for glaucoma such as age and elevated intra ocular pressure. This study will uncover regulators of mitochondrial functions that are affected in glaucomatous conditions which may constitute novel therapeutic targets.

Although the degeneration of retinal ganglion cells (RGCs) in Glaucoma is known to be triggered by a local insult in RGCs axons, very little is known on the molecular pathways affected by glaucomatous stress in specific RGCs sub-cellular locations. Our study will study the local mitochondrial pathways altered in specific RGC compartments during glaucoma.

Our study will uncover new mechanism altered in glaucoma which could provide an opportunity to design new treatments.