PHARMACOLOGICAL INHIBITION OF HDAC6 SUPPRESSES RETINAL INFLAMMATION AND PRESERVES VISUAL FUNCTION IN A BLUE LED-INDUCED RETINAL DEGENERATION MODEL

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide, in which chronic retinal inflammation driven by activated glial cells plays a pivotal role in disease progression. Histone deacetylase 6 (HDAC6), a cytoplasmic class IIb enzyme that primarily targets non-histone substrates, has been implicated in various neurodegenerative disorders; however, its role in retinal microglial inflammation remains poorly understood.
In this study, we investigated the therapeutic potential of tubastatin A (TubA), a selective HDAC6 inhibitor, using lipopolysaccharide (LPS)-stimulated microglia and a blue light–induced mouse model of retinal degeneration. BV2 microglial cells were pretreated with TubA prior to LPS stimulation, and inflammatory responses were evaluated by quantitative PCR and Western blot analysis. TubA markedly suppressed the expression of pro-inflammatory mediators, including Il-1β, Tnf-α, Mcp-1, and Mcp-5, and attenuated NF-κB nuclear translocation by promoting acetylation of the IKK complex in BV2 cells.
In vivo, TubA treatment significantly preserved retinal structure and visual function, as assessed by electroretinography, and reduced microglial activation in Balb/c mice exposed to blue light. Immunohistochemical analyses revealed pronounced upregulation of HDAC6 in activated retinal microglia following blue light exposure, which was further confirmed by Western blotting demonstrating increased HDAC6 protein levels in retinal tissue after LED-induced injury.
Collectively, these findings identify HDAC6 as a critical regulator of retinal microglial inflammatory responses and suggest that pharmacological inhibition of HDAC6 represents a promising therapeutic strategy for attenuating retinal degeneration and potentially slowing the progression of AMD.