ArticleMolecular medicine (Cambridge, Mass.)2012
Pigment epithelium-derived factor (PEDF) peptide eye drops reduce inflammation, cell death and vascular leakage in diabetic retinopathy in Ins2(Akita) mice.
Article in Molecular medicine (Cambridge, Mass.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
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Who cites it
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 128 citations in OpenAlex.
- Urinary and circulatory netrin-1 as biomarker in diabetes and its related complications: a systematic review and meta-analysis.Endocrine · 2024Pooled it
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Retinal glial cells in glaucoma and age-related retinal diseases: Inflammatory responses, disease transitions, and translational perspectives.Neural regeneration research · 2026Article
- Neuroprotection in Early Diabetic Retinal Disease Using Eyedrop Delivery.International journal of molecular sciences · 2026Review
- Eyedrop Administration of DPP-4 Inhibitors: A New Strategy for Treating Early Stages of Diabetic Retinal Disease.International journal of molecular sciences · 2026Review
- Complexity of PEDF multifunctional signaling in retinal development and diseases.Communications biology · 2026Article
- PEDF Prevents Corneal Endothelial Dysfunction of Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2026Article
- Neuroprotection in Diabetes Retinal Disease: An Unmet Medical Need.International journal of molecular sciences · 2026Review
- Review: The role of microglia in diabetic retinopathy and its potential as a therapeutic target.Molecular vision · 2026Review
- PANoptosis in diabetic retinopathy: immunological insights into mechanisms and translational therapies.Frontiers in immunology · 2026Review
- Understanding nonproliferative diabetic retinopathy progression using noninvasive imaging.Eye (London, England) · 2025Review
- Review
- H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.Communications medicine · 2025Article
- Loss of Pigment Epithelium Derived Factor Sensitizes C57BL/6J Mice to Light-Induced Retinal Damage.bioRxiv : the preprint server for biology · 2024Article
- Functional Roles of Pigment Epithelium-Derived Factor in Retinal Degenerative and Vascular Disorders: A Scoping Review.Investigative ophthalmology & visual science · 2024Article
- Sitagliptin eye drops prevent the impairment of retinal neurovascular unit in the new Trpv2Journal of neuroinflammation · 2024Article
- Relaxation of mitochondrial hyperfusion in the diabetic retina via N6-furfuryladenosine confers neuroprotection regardless of glycaemic status.Nature communications · 2024Article
- The Various Roles of PEDF in Cancer.Cancers · 2024Review
- Corneal application of SOCS1/3 peptides for the treatment of eye diseases mediated by inflammation and oxidative stress.Frontiers in immunology · 2024Review
- Mechanistic insights into the alterations and regulation of the AKT signaling pathway in diabetic retinopathy.Cell death discovery · 2023Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation, neurodegeneration and microvascular irregularities are included in the spectrum of defects associated with diabetic retinopathy. Here, we evaluated intraocular deliverability features of two pigment epithelium-derived factor (PEDF) derivatives given as eye drops and their efficacy in modulating diabetes-induced retinal complications. The antiangiogenic PEDF60-77 (P60) and neuroprotective PEDF78-121 (P78) derivatives were applied to Ins2(Akita) mouse eyes once a week for 15 wks at the onset of hyperglycemia. Peptides, labeled with Alexa Fluor 488, were observed penetrating the cornea by 1-4 h and gained access to the ciliary body, retinal pigment epithelium (RPE)-choroid complex, retina microvasculature and vitreous. Peak vitreous levels were 0.2 μg/mL for P60 and 0.9 μg/mL for P78 after 0.5 and 4 h, respectively. Both peptides reduced vascular leakage by ~60% and increased zona occludens 1 (ZO1) and occludin expression in the microvasculature to nondiabetic levels. P60 induced pERK1/2 and P78 promoted pAKT in Muller glia, two signals that were dampened in diabetic conditions. Pharmacologically inhibiting AKT signaling in the retina blocked effects of the peptides on ZO1 and occludin expression. P78 reduced levels of 9/20 cytokines in diabetic vitreous including interferon (IFN)-γ, interleukin (IL)-6, IL-3 and tumor necrosis factor (TNF)-α. P60 lowered levels of 6/20 cytokines but was less effective than P78. Neuroprotective P78 prevented diabetes-induced microglia activation by ~60%, retinal ganglion cell (RGC) death by ~22% and inner plexiform layer thinning by ~13%. In summary, we provide evidence that PEDF bioactive derivatives gained access to the retina by topical delivery and validated their efficacy in reducing diabetic retinopathy complications. Our findings argue for glia regulation of microvascular leakage and an early root cause for RGC degeneration embedded in microglia activation.
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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.