Fig. 4: Specific mechanisms by which m6A is associated with eye diseases.

In ocular tumors, such as retinoblastoma (RB), m6A regulates the cell cycle progression of retinoblastoma cells (RBC) and lens epithelial cells (LEC) by modulating the E2F3/RB pathway and hypoxia-inducible factor (HIF) [246]. In diabetic eye diseases, FTO regulates FoxO1 and NF-κB in an m6A-dependent manner, driving the pathological processes of diabetic retinopathy (DR) and diabetic cataract (DC) [3]. In inflammatory and immune eye diseases, m6A modification regulates the NLRP3 inflammasome, NF-κB pathway, and TNIP1, contributing to the pathogenesis of uveitis, fungal keratitis (FK), and thyroid-associated ophthalmopathy (TED)/Graves’ ophthalmopathy (GD) [141]. In glaucoma and optic nerve injury, m6A affects oxidative stress and FoxO1 signaling, participating in retinal ganglion cell (RGC) damage in primary open-angle glaucoma (PXG), ocular hypertension (TON), and traumatic optic neuropathy (TON) [2]. Additionally, m6A plays a key role in pathologic myopia (PM) through the HIF pathway in a hypoxic environment and in cataract formation by regulating ATF4 endoplasmic reticulum stress and SOD2 antioxidant defense mechanisms [299]. DC diabetic cataract, DR diabetic retinopathy, GD Graves’ disease, FK fungal keratitis, FTO fat mass and obesity associated protein, HIF hypoxia-Inducible factor, LEC lens epithelium cell, PM pathologic myopia, RB retinoblastoma, RBC retinoblastoma cell, RGC retinal ganglion cell, RIR retinal ischemia-reperfusion, ROS reactive oxygen species, TED thyroid eye disease, TON traumatic optic neuropathy.