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Digestion of the glycosaminoglycan extracellular matrix by chondroitinase ABC supports retinal ganglion cell dendritic preservation in a rodent model of experimental glaucoma

Tribble, James R., Williams, Pete A., Caterson, Bruce, Sengpiel, Frank and Morgan, James E. 2018. Digestion of the glycosaminoglycan extracellular matrix by chondroitinase ABC supports retinal ganglion cell dendritic preservation in a rodent model of experimental glaucoma. Molecular Brain 11 (1) , 69. 10.1186/s13041-018-0412-5

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Abstract

Retinal ganglion cell dendritic atrophy is an early feature of glaucoma, and the recovery of retinal ganglion cell dendrites is a viable option for vision improvement in glaucoma. Retinal ganglion cell neurites are surrounded by a specialised glycosaminoglycan extracellular matrix which inhibits dendritic plasticity. Since digestion of the extracellular matrix by chondroitinase ABC has been reported to have neuro-regenerative and neuro-plastic effects within the central nervous system, we explored its potential for dendritic recovery in a rat model of ocular hypertension. Chondroitinase ABC was administrated intravitreally 1 week after ocular hypertension (a time point where dendritic atrophy has already occurred). Retinal ganglion cell dendritic morphology was unaffected by chondroitinase ABC in normal retina. In ocular hypertensive eyes retinal ganglion cells showed significantly decreased dendritic length and area under the Sholl curve with atrophy confined to higher order dendrites. These changes were not observed in chondroitinase ABC injected eyes despite similar total retinal ganglion cell loss (i.e. dendritic protection of surviving retinal ganglion cells). These data suggest that glycosaminoglycan digestion could have a therapeutic role in mitigating the effects of elevated pressure on retinal ganglion cell dendritic structure in glaucoma.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: BioMed Central
ISSN: 1756-6606
Date of First Compliant Deposit: 4 December 2018
Date of Acceptance: 7 November 2018
Last Modified: 30 May 2019 22:09
URI: http://orca.cf.ac.uk/id/eprint/117348

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