{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yuan T"],"funding":["National Institutes of Health","NIH HHS"],"pagination":["3869"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9739170"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(23)"],"pubmed_abstract":["Microglial activation and subsequent pathological neuroinflammation contribute to diabetic retinopathy (DR). However, the underlying mechanisms of microgliosis, and means to effectively suppress pathological microgliosis, remain incompletely understood. Peroxisome proliferator-activated receptor alpha (PPARα) is a transcription factor that regulates lipid metabolism. The present study aimed to determine if PPARα affects pathological microgliosis in DR. In global <i>Pparα</i> mice, retinal microglia exhibited decreased structural complexity and enlarged cell bodies, suggesting microglial activation. Microglia-specific conditional <i>Pparα</i><sup>-/-</sup> (PCKO) mice showed decreased retinal thickness as revealed by optical coherence tomography. Under streptozotocin (STZ)-induced diabetes, diabetic PCKO mice exhibited decreased electroretinography response, while diabetes-induced retinal dysfunction was alleviated in diabetic microglia-specific <i>Pparα</i>-transgenic (PCTG) mice. Additionally, diabetes-induced retinal pericyte loss was exacerbated in diabetic PCKO mice and alleviated in diabetic PCTG mice. In cultured microglial cells with the diabetic stressor 4-HNE, metabolic flux analysis demonstrated that <i>Pparα</i> ablation caused a metabolic shift from oxidative phosphorylation to glycolysis. <i>Pparα</i> deficiency also increased microglial STING and TNF-α expression. Taken together, these findings revealed a critical role for PPARα in pathological microgliosis, neurodegeneration, and vascular damage in DR, providing insight into the underlying molecular mechanisms of microgliosis in this context and suggesting microglial PPARα as a potential therapeutic target."],"journal":["Cells"],"pubmed_title":["The Protective Role of Microglial PPARα in Diabetic Retinal Neurodegeneration and Neurovascular Dysfunction."],"pmcid":["PMC9739170"],"funding_grant_id":["EY032930","EY033477","EY028949","EY019309","EY012231","EY019309, EY012231, EY028949, EY030472, EY033330, EY032930, EY033477","EY033330","EY030472"],"pubmed_authors":["Yuan T","Pearsall EA","Ma JX","Cheng R","Dong L","Zhou K"],"additional_accession":[]},"is_claimable":false,"name":"The Protective Role of Microglial PPARα in Diabetic Retinal Neurodegeneration and Neurovascular Dysfunction.","description":"Microglial activation and subsequent pathological neuroinflammation contribute to diabetic retinopathy (DR). However, the underlying mechanisms of microgliosis, and means to effectively suppress pathological microgliosis, remain incompletely understood. Peroxisome proliferator-activated receptor alpha (PPARα) is a transcription factor that regulates lipid metabolism. The present study aimed to determine if PPARα affects pathological microgliosis in DR. In global <i>Pparα</i> mice, retinal microglia exhibited decreased structural complexity and enlarged cell bodies, suggesting microglial activation. Microglia-specific conditional <i>Pparα</i><sup>-/-</sup> (PCKO) mice showed decreased retinal thickness as revealed by optical coherence tomography. Under streptozotocin (STZ)-induced diabetes, diabetic PCKO mice exhibited decreased electroretinography response, while diabetes-induced retinal dysfunction was alleviated in diabetic microglia-specific <i>Pparα</i>-transgenic (PCTG) mice. Additionally, diabetes-induced retinal pericyte loss was exacerbated in diabetic PCKO mice and alleviated in diabetic PCTG mice. In cultured microglial cells with the diabetic stressor 4-HNE, metabolic flux analysis demonstrated that <i>Pparα</i> ablation caused a metabolic shift from oxidative phosphorylation to glycolysis. <i>Pparα</i> deficiency also increased microglial STING and TNF-α expression. Taken together, these findings revealed a critical role for PPARα in pathological microgliosis, neurodegeneration, and vascular damage in DR, providing insight into the underlying molecular mechanisms of microgliosis in this context and suggesting microglial PPARα as a potential therapeutic target.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-19T06:34:19.295Z","creation":"2025-04-19T06:34:19.295Z"},"accession":"S-EPMC9739170","cross_references":{"pubmed":["36497130"],"doi":["10.3390/cells11233869"]}}