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Article

Comparison of Glaucoma-Relevant Transcriptomic Datasets Identifies Novel Drug Targets for Retinal Ganglion Cell Neuroprotection

Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 171 64 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Contributed equally to this work.
Academic Editors: Miriam Kolko and Brent Siesky
J. Clin. Med. 2021, 10(17), 3938; https://doi.org/10.3390/jcm10173938
Received: 24 June 2021 / Revised: 10 August 2021 / Accepted: 27 August 2021 / Published: 31 August 2021
(This article belongs to the Special Issue Going for Gaps in Glaucoma)
Glaucoma is a leading cause of blindness and is characterized by the progressive dysfunction and irreversible death of retinal ganglion cells. We aimed to identify shared differentially expressed genes (DE genes) between different glaucoma relevant models of retinal ganglion cell injury using existing RNA-sequencing data, thereby discovering targets for neuroprotective therapies. A comparison of DE genes from publicly available transcriptomic datasets identified 12 shared DE genes. The Comparative Toxicogenomics Database (CTD) was screened for compounds targeting a significant proportion of the identified DE genes. Forty compounds were identified in the CTD that interact with >50% of these shared DE genes. We next validated this approach by testing select compounds for an effect on retinal ganglion cell survival using a mouse retinal explant model. Folic acid, genistein, SB-431542, valproic acid, and WY-14643 (pirinixic acid) were tested. Folic acid, valproic acid, and WY-14643 demonstrated significant protection against retinal ganglion cell death in this model. The increasing prevalence of open access-omics data presents a resource to discover targets for future therapeutic investigation. View Full-Text
Keywords: glaucoma; retinal ganglion cells; RNA-sequencing; neuroprotection; drug discovery glaucoma; retinal ganglion cells; RNA-sequencing; neuroprotection; drug discovery
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MDPI and ACS Style

Enz, T.J.; Tribble, J.R.; Williams, P.A. Comparison of Glaucoma-Relevant Transcriptomic Datasets Identifies Novel Drug Targets for Retinal Ganglion Cell Neuroprotection. J. Clin. Med. 2021, 10, 3938. https://doi.org/10.3390/jcm10173938

AMA Style

Enz TJ, Tribble JR, Williams PA. Comparison of Glaucoma-Relevant Transcriptomic Datasets Identifies Novel Drug Targets for Retinal Ganglion Cell Neuroprotection. Journal of Clinical Medicine. 2021; 10(17):3938. https://doi.org/10.3390/jcm10173938

Chicago/Turabian Style

Enz, Tim J., James R. Tribble, and Pete A. Williams. 2021. "Comparison of Glaucoma-Relevant Transcriptomic Datasets Identifies Novel Drug Targets for Retinal Ganglion Cell Neuroprotection" Journal of Clinical Medicine 10, no. 17: 3938. https://doi.org/10.3390/jcm10173938

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