HMG-CoA reductase inhibitors (statin) prevents retinal neovascularization in a model of oxygen-induced retinopathy

Manuela Bartoli, Mohamed Al-Shabrawey, Mohamed Labazi, M. Ali Behzadian, Mohamed Istanboli, Azza B. El-Remessy, Robert William Caldwell, Dennis M. Marcus, Ruth B Caldwell

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

PURPOSE. Retinal neovascularization (RNV) is a primary cause of blindness and involves the dysfunction of retinal capillaries. Recent studies have emphasized the beneficial effects of inhibitors of HMG-CoA reductase (statins) in preventing vascular dysfunction. In the present study, the authors characterized the therapeutic effects of statins on RNV. METHODS. Statin treatment (10 mg/kg/d fluvastatin) was tested in a mouse model of oxygen-induced retinopathy. Morphometric analysis was conducted to determine the extent of capillary growth. Pimonidazole hydrochloride was used to assess retinal ischemia. Western blot and immunohistochemical analyses were used to assess protein expression levels and immunolocalization. Lipid peroxidation and superoxide radical formation were determined to assess oxidative changes. RESULTS. Fluvastatin treatment significantly reduced the area of the capillary-free zone (P < 0.01), decreased the formation of neovascular tufts (P < 0.01), and ameliorated retinal ischemia. These morphologic and functional changes were associated with statin effects in preventing the upregulation of VEGF, HIF-1α, phosphorylated STAT3, and vascular expression of the inflammatory mediator ICAM-1 (P < 0.01). Superoxide production and lipid peroxidation in the ischemic retina were also reduced by statin treatment (P < 0.01). CONCLUSIONS. These data suggest the beneficial effects of statin treatment in preventing retinal eovascularization. These beneficial effects appear to result from the anti-oxidant and anti-inflammatory properties of statins.

Original languageEnglish (US)
Pages (from-to)4934-4940
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number10
DOIs
StatePublished - Dec 1 2009

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Retinal Neovascularization
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Oxygen
fluvastatin
Superoxides
Lipid Peroxidation
Blood Vessels
Ischemia
Therapeutic Uses
Intercellular Adhesion Molecule-1
Blindness
Oxidants
Vascular Endothelial Growth Factor A
Retina
Anti-Inflammatory Agents
Up-Regulation
Western Blotting
Growth

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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HMG-CoA reductase inhibitors (statin) prevents retinal neovascularization in a model of oxygen-induced retinopathy. / Bartoli, Manuela; Al-Shabrawey, Mohamed; Labazi, Mohamed; Ali Behzadian, M.; Istanboli, Mohamed; El-Remessy, Azza B.; Caldwell, Robert William; Marcus, Dennis M.; Caldwell, Ruth B.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 10, 01.12.2009, p. 4934-4940.

Research output: Contribution to journalArticle

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abstract = "PURPOSE. Retinal neovascularization (RNV) is a primary cause of blindness and involves the dysfunction of retinal capillaries. Recent studies have emphasized the beneficial effects of inhibitors of HMG-CoA reductase (statins) in preventing vascular dysfunction. In the present study, the authors characterized the therapeutic effects of statins on RNV. METHODS. Statin treatment (10 mg/kg/d fluvastatin) was tested in a mouse model of oxygen-induced retinopathy. Morphometric analysis was conducted to determine the extent of capillary growth. Pimonidazole hydrochloride was used to assess retinal ischemia. Western blot and immunohistochemical analyses were used to assess protein expression levels and immunolocalization. Lipid peroxidation and superoxide radical formation were determined to assess oxidative changes. RESULTS. Fluvastatin treatment significantly reduced the area of the capillary-free zone (P < 0.01), decreased the formation of neovascular tufts (P < 0.01), and ameliorated retinal ischemia. These morphologic and functional changes were associated with statin effects in preventing the upregulation of VEGF, HIF-1α, phosphorylated STAT3, and vascular expression of the inflammatory mediator ICAM-1 (P < 0.01). Superoxide production and lipid peroxidation in the ischemic retina were also reduced by statin treatment (P < 0.01). CONCLUSIONS. These data suggest the beneficial effects of statin treatment in preventing retinal eovascularization. These beneficial effects appear to result from the anti-oxidant and anti-inflammatory properties of statins.",
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AU - Istanboli, Mohamed

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