Mitochondrial morphology and motility in retinal ganglion cells

Sun, Shanshan 2021. Mitochondrial morphology and motility in retinal ganglion cells. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

OPA1 is the key regulator for the mitochondrial fusion and fission balance and also plays an important role in the pathological process of ADOA, causing visual dysfunction and even systemic disabilities. Retinal ganglion cells (RGCs) are vulnerable to energy disturbances, preferentially affected in most ADOA patients. The precise role of mitochondrial dynamics in retinal ganglion cell health and progression of cell death remains unclear. Thus, in this thesis it is hypothesized that alterations in mitochondrial dynamics during the early asymptomatic stages of ADOA precede the neurodegeneration and consequent RGC death. Utilising immunofluorescence, time-lapse imaging and measurement of oxygen consumption rates, it was found that Opa1 deficiency leads to significant fragmentation of mitochondrial morphology, activation of mitochondrial motility and impaired respiratory function in RGCs from the B6; C3-Opa1Q285STOP mouse model. The increased motility of mitochondria is hypothesized to be a spontaneous compensatory response which promotes fusion activity and facilitates energy production. This result highlights the significant alterations in the intricate interplay between mitochondrial morphology, motility, and energy production in RGCs with Opa1 deficiency long before the onset of clinical symptoms of the pathology. In order to explore and gain a better understanding of mitochondrial morphology and motility in RGCs under different conditions, hypertensive stress and drug administration were applied to RGCs in vitro. In the in vitro hypertension model, it was found that hypertensive stress caused shortened length of mitochondrial structures accompanied with increased mitochondrial motility. By applying nicotinamide directly into the RGC culture medium in vitro with different concentrations for 24 hours, it was found that nicotinamide increased the percentage of motile mitochondria in neurites of RGCs as well as the velocities of mitochondrial movement.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Optometry and Vision Sciences
Subjects:	R Medicine > RE Ophthalmology
Uncontrolled Keywords:	: Mitochondrial dynamics, retinal ganglion cells, Opa1, hypertensive stress, nicotinamide
Date of First Compliant Deposit:	28 June 2021
Last Modified:	19 May 2023 01:18
URI:	https://orca.cardiff.ac.uk/id/eprint/142140

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