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Characterisation and validation of the 8-fold quadrant dissected human retinal explant culture model for pre-clinical toxicology investigation

journal contribution
posted on 03.02.2020, 00:00 by A Murali, Charmaine Ramlogan-Steel, Jason Steel, CJ Layton
© 2019 One of the major challenges in studying ocular toxicology is a lack of clinically-relevant retinal experimental models. In this study we describe the use of an in vitro human retinal explant strategy to generate a reproducible experimental model with utility in neuro-toxicity retinal studies. A retinal dissection strategy, referred to as the 8 fold quadrant dissection, was developed by dissecting human donor retinas into 4 fragments through the fovea in order to obtain 8 experimentally reproducible retinal explants from a single donor. This quadrant dissection gave rise to equivalent proportions of CD73+ photoreceptors and CD90+ ganglion cells in 8 fragments from a single donor and this remained stable for up to 3 days in culture. Major retinal cell types continued to be observed after 8 weeks in culture, despite breakdown of the retinal layers, suggesting the potential to use this model in long-term studies where observation of individual cell types is possible. The utility of this system was examined in a proof of principle neuro-toxicology study. We showed reproducible induction of toxicity in photoreceptors and retinal ganglion cells by glutamate, cobalt chloride and hydrogen peroxide insults, and observed the therapeutic positive effects of the administration of memantine, formononetin and trolox. The quadrant dissected human retinal explants have the potential to be used in toxicology studies in human ocular diseases.

Funding

Category 3 - Industry and Other Research Income

History

Volume

63

Start Page

1

End Page

10

Number of Pages

10

eISSN

1879-3177

ISSN

0887-2333

Publisher

Elsevier, UK

Peer Reviewed

Yes

Open Access

No

Acceptance Date

04/11/2019

External Author Affiliations

University of Queensland; LVF Ophthalmology Research Centre, Qld

Era Eligible

Yes

Journal

Toxicology in Vitro

Usage metrics

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