Prior　research　has　demonstrated　the　therapeutic　potential　of　peroxisome　proliferator-activated　receptor　α　(PPARα)　agonist　fenofibrate　on　diabetic　retinopathy.　In　the　present　study,　a　novel　non-fibrate　PPARα　agonist,　A190,　was　designed　with　higher　potency　and　selectivity　than　fenofibrate　in　PPARα　agonism.　A190　was　encapsulated　in　biodegradable　microparticles　(A190-MP)　to　ensure　sustained　drug　release,　with　detection　in　the　retina　up　to　6　months　following　a　single　intravitreal　injection.　A190-MP　alleviated　retinal　dysfunction　as　shown　by　electroretinography　in　Vldlr−/−　(wet-AMD　model)　and　Abca4−/−/Rdh8−/−　(dry-AMD　model)　mice.　A190-MP　also　attenuated　the　decreases　in　cone　photoreceptor　density　and　outer　nuclear　layer　thickness　as　demonstrated　by　optical　coherence　tomography　and　histology.　Moreover,　A190-MP　reduced　vascular　leakage　and　neovascularization　in　Vldlr−/−　mice,　suggesting　an　anti-inflammatory　and　anti-angiogenic　effect.　A190-MP　upregulated　expression　of　PPARα,　PGC1α,　and　TOMM20　in　the　retina　of　Vldlr−/−　and　Abca4−/−/Rdh8−/−　mice.　A190-MP　also　improved　retinal　mitochondrial　function　as　shown　by　Seahorse　analysis　using　retinal　biopsy.　In　vitro,　A190　attenuated　oxidative　stress　and　preserved　cell　viability　in　a　photoreceptor-derived　cell　line　exposed　to　4-HNE　and　improved　mitochondrial　function,　via　a　PPARα-dependent　mechanism.　These　findings　revealed　sustained　therapeutic　effects　of　A190-MP　in　wet　and　dry　AMD　models,　through　improving　mitochondrial　function　by　activating　PPARα.　©　2025