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Valproic acid has previously been demonstrated to reduce neuroinflammation and is neuroprotective in a number of experimental settings. To determine whether valproic acid can limit retinal neuroinflammation and protect retinal neurons we used an <jats:italic>ex vivo<\/jats:italic> retina explant (axotomy) model to isolate resident glial responses from blood-derived monocytes. Neuroinflammatory status was defined using high resolution confocal imaging with 3D morphological reconstruction and cytokine protein arrays. Valproic acid significantly reduced microglia and astrocyte morphological changes, consistent with a reduction in pro-inflammatory phenotypes. Cytokine profiling demonstrated that valproic acid significantly attenuated or prevented expression of pro-inflammatory cytokines in injured retina. This identifies that the retinal explant model as a useful tool to explore resident neuroinflammation in a rapid timescale whilst maintaining a complex system of cell interactions and valproic acid as a useful drug to further explore anti-neuroinflammatory strategies in retinal disease.<\/jats:p>","DOI":"10.3389\/fcell.2022.903436","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T06:58:14Z","timestamp":1652338694000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Valproic Acid Reduces Neuroinflammation to Provide Retinal Ganglion Cell Neuroprotection in the Retina Axotomy Model"],"prefix":"10.3389","volume":"10","author":[{"given":"James R.","family":"Tribble","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Kastanaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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