Retinitis pigmentosa (RP) is an outer retinal degenerative disease that can lead to photoreceptor cell death and profound vision loss. Although effective regulation of intraretinal inflammation can slow down the progression of the disease, an efficient anti-inflammatory treatment strategy is still lacking. This study reports the fabrication of a hyaluronic acid-based inflammation-responsive hydrogel (IRH) and its epigenetic regulation effects on retinal degeneration. The injectable IRH was designed to respond to cathepsin overexpression in an inflammatory environment. The epigenetic drug, the enhancer of zeste homolog 2 (EZH2) inhibitors, was loaded into the hydrogel to attenuate inflammatory factors. On-demand anti-inflammatory effects of microglia cells via the drug-loaded IRH were verified in vitro and in vivo retinal degeneration 10 (rd10) mice model. Therefore, our IRH not only reduced intraretinal inflammation but also protected photoreceptors morphologically and functionally. Our results suggest the IRH reported here can be used to considerably delay vision loss caused by RP.

色素性视网膜炎 (RP) 是一种外层视网膜退行性疾病，可导致感光细胞死亡和严重视力丧失。虽然有效调节视网膜内炎症可以减缓疾病的进展，但仍缺乏有效的抗炎治疗策略。这项研究报告了基于透明质酸的炎症反应性水凝胶（IRH）的制造及其对视网膜变性的表观遗传调控作用。可注射的 IRH 旨在响应炎症环境中组织蛋白酶的过度表达。表观遗传药物是 zeste 同源物 2 (EZH2) 抑制剂的增强剂，被加载到水凝胶中以减弱炎症因子。小胶质细胞通过载药 IRH 的按需抗炎作用在体外和体内视网膜变性 10 (rd10) 小鼠模型中得到验证。因此，我们的 IRH 不仅减少了视网膜内炎症，而且从形态和功能上保护了光感受器。我们的结果表明，此处报告的 IRH 可用于显着延缓 RP 引起的视力丧失。