Midget retinal ganglion cell dendritic and mitochondrial degeneration is an early feature of human glaucoma

Tribble, James R., Vasalauskaite, Asta, Redmond, Tony ORCID: https://orcid.org/0000-0002-6997-5231, Young, Robert D., Hassan, Shoaib, Fautsch, Michael P., Sengpiel, Frank ORCID: https://orcid.org/0000-0002-7060-1851, Williams, Pete A. and Morgan, James E. ORCID: https://orcid.org/0000-0002-8920-1065 2019. Midget retinal ganglion cell dendritic and mitochondrial degeneration is an early feature of human glaucoma. Brain Communications 1 (1) , fcz035. 10.1093/braincomms/fcz035

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Abstract

Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells. However, the earliest degenerative events that occur in human glaucoma are relatively unknown. Work in animal models has demonstrated that retinal ganglion cell dendrites remodel and atrophy prior to the loss of the cell soma. Whether this occurs in human glaucoma has yet to be elucidated. Serial block face scanning electron microscopy is well established as a method to determine neuronal connectivity at high resolution but so far has only been performed in normal retina from model animals. To assess the structure-function relationship of early human glaucomatous neurodegeneration, regions of inner retina assessed to have none-to-moderate loss of retinal ganglion cell number were processed using serial block face scanning electron microscopy (n = 4 normal retinas, n = 4 glaucoma retinas). This allowed detailed 3D reconstruction of retinal ganglion cells and their intracellular components at a nanometer scale. In our datasets retinal ganglion cell dendrites degenerate early in human glaucoma, with remodeling and redistribution of the mitochondria. We assessed the relationship between visual sensitivity and retinal ganglion cell density and discovered that this only partially conformed to predicted models of structure-function relationships, which may be affected by these early neurodegenerative changes. In this study, human glaucomatous retinal ganglion cells demonstrate compartmentalized degenerative changes as observed in animal models. Importantly, in these models, many of these changes have been demonstrated to be reversible, increasing the likelihood of translation to viable therapies for human glaucoma.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences Medicine Biosciences
Publisher:	Oxford University Press
ISSN:	2632-1297
Funders:	Fight for Sight, UK (1580/1581, JEM); Medical Research Council, UK (1221470, FS); National Eye Institute, US (EY21727 and EY26490, MPF); Karolinska Institutet, Board of Research Faculty Fund (PAW); Vetenskapsrådet 2018-02124 (PAW); Medical Research Council, UK (MR/K000837/1, Keith Meek; operational costs of SBFSEM)
Date of First Compliant Deposit:	20 December 2019
Date of Acceptance:	1 November 2019
Last Modified:	06 May 2023 04:13
URI:	https://orca.cardiff.ac.uk/id/eprint/127679

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