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Cited by 94Retinal Diseases and TreatmentsSirtuins and Resveratrol in MedicineAngiogenesis and VEGF in Cancer

Resveratrol Inhibits Pathologic Retinal Neovascularization in Vldlr−/−Mice

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Hua, Jing, Guerin, Karen I., Chen, Jing, Michán, Shaday, Stahl, Andreas, Krah, Nathan M., Seaward, Molly R., Dennison, Roberta J. +5 more·2011·Investigative Opthalmology & Visual Science
DOI 10.1167/iovs.10-6496PMC PMC3088563
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Abstract

PURPOSE: Macular telangiectasia (MacTel) is a vision-threatening retinal disease with unknown pathogenesis and no approved treatment. Very low-density lipoprotein receptor mutant mice (Vldlr(-/-)) exhibit critical features of MacTel such as retinal neovascularization and photoreceptor degeneration. In this study, the authors evaluate the therapeutic potential of resveratrol, a plant polyphenol, in Vldlr(-/-) mice as a model for MacTel. METHODS: Vldlr(-/-) and wild-type mice at postnatal day (P) 21 to P60 or P10 to P30 were treated orally with resveratrol. The number of neovascular lesions was evaluated on retinal flatmounts, and resveratrol effects on endothelial cells were assessed by Western blot for phosphorylated ERK1/2, aortic ring, and migration assays. Vegf and Gfap expression was evaluated in laser-capture microdissected retinal layers of angiogenic lesions and nonlesion areas from Vldlr(-/-) and wild-type retinas. RESULTS: From P15 onward, Vldlr(-/-) retinas develop vascular lesions associated with the local upregulation of Vegf in photoreceptors and Gfap in the inner retina. Oral resveratrol reduces lesion formation when administered either before or after disease onset. The reduction of vascular lesions in resveratrol-treated Vldlr(-/-) mice is associated with the suppression of retinal Vegf transcription. Resveratrol also reduces endothelial ERK1/2 signaling as well as the migration and proliferation of endothelial cells. Furthermore, a trend toward increased rhodopsin mRNA in Vldlr(-/-) retinas is observed. CONCLUSIONS: Oral administration of resveratrol is protective against retinal neovascular lesions in Vldlr(-/-) mice by inhibiting Vegf expression and angiogenic activation of retinal endothelial cells. These results suggest that resveratrol might be a safe and effective intervention for treating patients with MacTel.

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  • The MAPK signaling pathway plays a crucial role in the pathogenesis and progression of AMD.

    “Emerging evidence suggests that the MAPK signaling pathway plays a crucial role in the pathogenesis and progression of AMD 34-36 .”

    From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [36]

    The section “Resveratrol Inhibits Endothelial Cell Migration and ERK1/2 Phosphorylation” (page not provided) links ERK1/2 MAPK signaling to VEGF-induced endothelial migration and proliferation. But the study examines a mouse model of macular telangiectasia, not AMD, and does not establish that MAPK plays a crucial role in AMD pathogenesis or progression. (LLM, conf=0.85)

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Cited by

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Authors
Hua, J., Guerin, K. I., Chen, J., Michán, S., Stahl, A., Krah, N. M., Seaward, M. R., Dennison, R. J., Juan, A. M., Hatton, C. J., Sapieha, P., Sinclair, D. A., & Smith, L. E. H.
Affiliations
  • Boston Children's Hospital (US)
  • Harvard University (US)
Corresponding author
  • Hua, Jing
  • Guerin, Karen I.
  • Chen, Jing
  • Michán, Shaday
  • Stahl, Andreas
  • Krah, Nathan M.
  • Seaward, Molly R.
  • Dennison, Roberta J.
  • Juan, Aimee M.
  • Hatton, Colman J.
  • Sapieha, Przemyslaw
  • Sinclair, David A.
  • Smith, Lois E. H.
ORCID
Venue
Investigative Opthalmology & Visual Science
Publisher
Association for Research in Vision and Ophthalmology (ARVO)
Published
2011-04-25
Volume
52
Issue
5
Pages
2809
ISSN
  • 0146-0404 (ISSN-L)
  • 1552-5783
DOI
10.1167/iovs.10-6496
PMC
PMC3088563
OpenAlex
W2054025498
Cited by
94
References
3
Citations by year
2026: 7 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 8 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 10
FWCI
6.90
Type
journal article
Language
en
Open access
Locations
  • Investigative Ophthalmology & Visual Science (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • Ellison Medical Foundation
  • Juvenile Diabetes Research Foundation International
  • Glenn Foundation for Medical Research
  • V. Kann Rasmussen Foundation (EY017017)
  • Charles A. King Trust
  • Ögonfonden
  • Deutsche Forschungsgemeinschaft
  • Fondation pour la Recherche Médicale
  • National Institutes of Health (AG027916, AG028730)
  • Manton Center for Orphan Disease Research, Boston Children's Hospital
  • Canadian Institutes of Health Research
  • National Institute on Aging (R37AG028730, P01AG027916, R01AG028730, R01AG019719, AG028730, AG027916)
  • National Eye Institute (EY017017-S1, EY017017, R01EY017017)
  • Alcon Research Institute
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
resveratrol, macular telangiectasia, retinal neovascularization, VLDLR, vascular endothelial growth factor, ERK signaling, retinal endothelial cells, angiogenesis, photoreceptor degeneration, rhodopsin, glial fibrillary acidic protein
MeSH terms
Resveratrol, Administration, Oral, Animals, Antioxidants, Disease Models, Animal, Endothelium, Vascular, Female, Glial Fibrillary Acidic Protein, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Receptors, LDL, Retina, RNA, Messenger, Stilbenes, Blotting, Western, Retinal Neovascularization, Mice, Knockout, Fluorescent Antibody Technique, Indirect, Reverse Transcriptase Polymerase Chain Reaction, Angiogenesis Inhibitors, Vascular Endothelial Growth Factor A, Mice, Retinal Telangiectasis

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