Peroxisomal dynamics in degenerative retinopathies: implications of retinal lipid metabolism and therapeutic...

Peroxisomes are a type of organelles essential for metabolic activities. They are extensively distributed in retinal tissue and play a core role in biomolecular synthesis, cellular metabolism, oxidative stress, and immune defense. Patients suffering from peroxisomal disorders will exhibit a number of ocular symptoms, including degenerative retinopathy, cataract, glaucoma, and optic nerve abnormalities. Specifically, pathological stimuli such as oxidative stress, aging-related metabolic decline, genetic mutations, and hyperglycemia induce the decline of peroxisomal biogenesis, coupled with disrupted activity of lipid metabolic enzymes, leading to aberrant peroxisomal function and expression. This impairment further triggers lipid metabolic dysregulation and heightened oxidative stress, which sequentially contribute to the development of degenerative retinopathy. This review comprehensively delves into the functions of peroxisomes in retinal lipid metabolism and reduction-oxidation balance. These findings may help to uncover the exact mechanism through which peroxisomal dysfunction initiates retinal pathologies. Furthermore, emerging therapeutic strategies targeting peroxisomes are also introduced in this review. These strategies can promote the transformation from symptomatic alleviation to mechanistic intervention for organelle dysfunction in degenerative retinopathy. Future studies should concentrate on clarifying the cell-type specific functions of peroxisomes in retina, deciphering the complicated interplay between peroxisomes and other organelles, thereby optimizing the efficiency of peroxisome-targeted therapeutics.