Valproic Acid Reduces Neuroinflammation to Provide Retinal Ganglion Cell Neuroprotection in the Retina Axotomy Model

Neuroinflammation is a critical and targetable pathogenic component of neurodegenerative diseases, including glaucoma, the leading cause of irreversible blindness. 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 ex vivo 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.