ArticlePloS one2019
Neuroprotective effects of PPARα in retinopathy of type 1 diabetes.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 45 citations in OpenAlex.
- Network Analysis of Convergent and Specific Molecular Pathways of Nutraceuticals with Antioxidant and Neuroprotective Potential in Glaucoma.Antioxidants (Basel, Switzerland) · 2026Article
- Long-acting fenofibrate-loaded microparticles for treating retinal disorders.International journal of pharmaceutics · 2026Article
- Neuroprotection in Diabetes Retinal Disease: An Unmet Medical Need.International journal of molecular sciences · 2026Review
- Fenofibrate in ophthalmology: therapeutic efficacy and mechanisms.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- Review
- Early-stage diabetic retinopathy: gut-metabolic triggers, immune-neurodegeneration, and interventions.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Review
- Neuroprotective Effect of a Novel Soluble Guanylate Cyclase Activator Runcaciguat in Diabetic and Ischemic Retinopathy.Diabetes · 2025Article
- Sustained release of a novel non-fibrate PPARα agonist from microparticles for neuroprotection in murine models of age-related macular degeneration.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Future Directions in Diabetic Retinopathy Treatment: Stem Cell Therapy, Nanotechnology, and PPARα Modulation.Journal of clinical medicine · 2025Review
- Therapeutic effects of selenium nanoparticles versus selenium on experimentally induced diabetic retinopathy via modulation of TLR4 / NF-Tissue barriers · 2025Article
- Article
- Oxidative stress in the eye and its role in the pathophysiology of ocular diseases.Redox biology · 2023Review
- Retinal Cell Damage in Diabetic Retinopathy.Cells · 2023Review
- Therapeutic roles of PPARα activation in ocular ischemic diseases.Histology and histopathology · 2023Review
- PPAR-α Agonist Fenofibrate Ameliorates Sjögren Syndrome-Like Dacryoadenitis by Modulating Th1/Th17 and Treg Cell Responses in NOD Mice.Investigative ophthalmology & visual science · 2022Article
- The Effect of Hyperlipidemia on the Course of Diabetic Retinopathy-Literature Review.Journal of clinical medicine · 2022Review
- Lipids, hyperreflective crystalline deposits and diabetic retinopathy: potential systemic and retinal-specific effect of lipid-lowering therapies.Diabetologia · 2022Review
- Fenofibrate Nano-Eyedrops Ameliorate Retinal Blood Flow Dysregulation and Neurovascular Coupling in Type 2 Diabetic Mice.Pharmaceutics · 2022Article
- PPARα Modulation-Based Therapy in Central Nervous System Diseases.Life (Basel, Switzerland) · 2021Review
- The role of peroxisome proliferator-activated receptors in healthy and diseased eyes.Experimental eye research · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Diabetic retinopathy (DR) is a common neurovascular complication of type 1 diabetes. Current therapeutics target neovascularization characteristic of end-stage disease, but are associated with significant adverse effects. Targeting early events of DR such as neurodegeneration may lead to safer and more effective approaches to treatment. Two independent prospective clinical trials unexpectedly identified that the PPARα agonist fenofibrate had unprecedented therapeutic effects in DR, but gave little insight into the physiological and molecular mechanisms of action. The objective of the present study was to evaluate potential neuroprotective effects of PPARα in DR, and subsequently to identify the responsible mechanism of action. Here we reveal that activation of PPARα had a robust protective effect on retinal function as shown by Optokinetic tracking in a rat model of type 1 diabetes, and also decreased retinal cell death, as demonstrated by a DNA fragmentation ELISA. Further, PPARα ablation exacerbated diabetes-induced decline of visual function as demonstrated by ERG analysis. We further found that PPARα improved mitochondrial efficiency in DR, and decreased ROS production and cell death in cultured retinal neurons. Oxidative stress biomarkers were elevated in diabetic Pparα-/- mice, suggesting increased oxidative stress. Mitochondrially mediated apoptosis and oxidative stress secondary to mitochondrial dysfunction contribute to neurodegeneration in DR. Taken together, these findings identify a robust neuroprotective effect for PPARα in DR, which may be due to improved mitochondrial function and subsequent alleviation of energetic deficits, oxidative stress and mitochondrially mediated apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.