The Influence of Mitochondrial Dynamics and Function on Retinal Ganglion Cell Susceptibility in Optic Nerve Disease
Open Access
- 24 June 2021
- Vol. 10 (7), 1593
- https://doi.org/10.3390/cells10071593
Abstract
The important roles of mitochondrial function and dysfunction in the process of neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type in the central nervous system with respect to mitochondrial dysfunction but the actual reasons for this are still incompletely understood. These cells have a unique circumstance where unmyelinated axons must bend nearly 90° to exit the eye and then cross a translaminar pressure gradient before becoming myelinated in the optic nerve. This region, the optic nerve head, contains some of the highest density of mitochondria present in these cells. Glaucoma represents a perfect storm of events occurring at this location, with a combination of changes in the translaminar pressure gradient and reassignment of the metabolic support functions of supporting glia, which appears to apply increased metabolic stress to the RGC axons leading to a failure of axonal transport mechanisms. However, RGCs themselves are also extremely sensitive to genetic mutations, particularly in genes affecting mitochondrial dynamics and mitochondrial clearance. These mutations, which systemically affect the mitochondria in every cell, often lead to an optic neuropathy as the sole pathologic defect in affected patients. This review summarizes knowledge of mitochondrial structure and function, the known energy demands of neurons in general, and places these in the context of normal and pathological characteristics of mitochondria attributed to RGCs.Keywords
Funding Information
- National Eye Institute (R01EY030123, R01EY022086, P30EY016665, T32EY027721)
- Research to Prevent Blindness (Unrestricted Grant)
- Department of Ophthalmology and Visual Sciences, UW-Madison (Frederick A. Davis Research Chair, Timothy William Trout Research Chair)
This publication has 221 references indexed in Scilit:
- The Hallmarks of AgingCell, 2013
- Confirmation of TBK1 duplication in normal tension glaucomaExperimental Eye Research, 2012
- The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucomaActa Neuropathologica, 2011
- The Soluble Form of Bax Regulates Mitochondrial Fusion via MFN2 Homotypic ComplexesMolecular Cell, 2011
- Mitochondrial dysfunction in amyotrophic lateral sclerosisBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2010
- Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neuronsExperimental Neurology, 2009
- Mitochondrial structural and functional dynamics in Huntington's diseaseBrain Research Reviews, 2009
- The morphology and spatial arrangement of astrocytes in the optic nerve head of the mouseJournal of Comparative Neurology, 2009
- Miro1 Is a Calcium Sensor for Glutamate Receptor-Dependent Localization of Mitochondria at SynapsesNeuron, 2009
- The Mechanism of Ca2+-Dependent Regulation of Kinesin-Mediated Mitochondrial MotilityCell, 2009