ArticleDiabetologia2011
Diabetes-induced peroxynitrite impairs the balance of pro-nerve growth factor and nerve growth factor, and causes neurovascular injury.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 111 citations in OpenAlex.
- Beyond hyperglycaemia: diabetic retinopathy is a multifactorial complication of diabetes mellitus.Annals of medicine · 2026Review
- Nerve Growth Factor in Diabetes Mellitus: Pathophysiological Mechanisms, Biomarkers and Therapeutic Opportunities.Pharmaceuticals (Basel, Switzerland) · 2025Review
- DJ-1 Protects Human Retinal Endothelial Cells From Diabetes-Related Conditions and Prevents Ischemic Damage in Mouse Retinal Capillaries.Investigative ophthalmology & visual science · 2025Article
- Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches.Frontiers in immunology · 2025Review
- Article
- Cell and molecular targeted therapies for diabetic retinopathy.Frontiers in endocrinology · 2024Review
- Sortilin Inhibition Protects Neurons From Degeneration in the Diabetic Retina.Investigative ophthalmology & visual science · 2023Article
- Role of Oxidative Stress in Ocular Diseases: A Balancing Act.Metabolites · 2023Review
- The Protective Effects of Neurotrophins and MicroRNA in Diabetic Retinopathy, Nephropathy and Heart Failure via Regulating Endothelial Function.Biomolecules · 2022Review
- Pro Nerve Growth Factor and Its Receptor p75NTR Activate Inflammatory Responses in Synovial Fibroblasts: A Novel Targetable Mechanism in Arthritis.Frontiers in immunology · 2022Article
- The innate immune system in diabetic retinopathy.Progress in retinal and eye research · 2021Review
- The stress response protein REDD1 as a causal factor for oxidative stress in diabetic retinopathy.Free radical biology & medicine · 2021Review
- Salusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- Electroacupuncture Pretreatment Regulates Apoptosis of Myocardial Ischemia-Reperfusion Injury in Rats Through RhoA/p38MAPK Pathway Mediated by miR-133a-5p.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Antagonism of proNGF or its receptor p75Diabetologia · 2020Article
- Article
- Carbamazepine Alleviates Retinal and Optic Nerve Neural Degeneration in Diabetic Mice via Nerve Growth Factor-Induced PI3K/Akt/mTOR Activation.Frontiers in neuroscience · 2019Article
- Deletion of p75Scientific reports · 2018Article
- PROneurotrophins and CONSequences.Molecular neurobiology · 2018Review
- Role of Inflammation in Diabetic Retinopathy.International journal of molecular sciences · 2018Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisDiabetic retinopathy, the leading cause of blindness in working-age Americans, is characterised by reduced neurotrophic support and increased proinflammatory cytokines, resulting in neurotoxicity and vascular permeability. We sought to elucidate how oxidative stress impairs homeostasis of nerve growth factor (NGF) and its precursor, proform of NGF (proNGF), to cause neurovascular dysfunction in the eye of diabetic patients.
methodsLevels of NGF and proNGF were examined in samples from human patients, from retinal Müller glial cell line culture cells and from streptozotocin-induced diabetic animals treated with and without atorvastatin (10 mg/kg daily, per os) or 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinato iron (III) chloride (FeTPPs) (15 mg/kg daily, i.p.) for 4 weeks. Neuronal death and vascular permeability were assessed by TUNEL and extravasation of BSA-fluorescein.
resultsDiabetes-induced peroxynitrite formation impaired production and activity of matrix metalloproteinase-7 (MMP-7), which cleaves proNGF extracellularly, leading to accumulation of proNGF and reducing NGF in samples from diabetic retinopathy patients and experimental models. Treatment of diabetic animals with atorvastatin exerted similar protective effects that blocked peroxynitrite using FeTPPs, restoring activity of MMP-7 and hence the balance between proNGF and NGF. These effects were associated with preservation of blood-retinal barrier integrity, preventing neuronal cell death and blocking activation of RhoA and p38 mitogen-activated protein kinase (p38MAPK) in experimental and human samples. CONCLUSIONS/
interpretationOxidative stress plays an unrecognised role in causing accumulation of proNGF, which can activate a common pathway, RhoA/p38MAPK, to mediate neurovascular injury. Oral statin therapy shows promise for treatment of diabetic retinopathy.
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