Here, we report TRIOL as a novel marine neuroprotectant that can protect RGCs from acute I/R injury via inhibiting microglial activation by enhancing the Nrf2/HO-1 pathway in the acute intraocular hypertension (AIH) model, which may provide new insights and a promising candidate agent for the therapeutics of acute glaucoma. The gene discussed is HMOX1; the disease is autoimmune hepatitis.