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

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-1 alpha, 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 neovascularization. These beneficial effects appear to result from the anti-oxidant and anti-inflammatory properties of statins.

• Authors: Manuela Bartoli, Mohamed Al-Shabrawey, Mohamed Labazi, M Ali Behzadian, Mohamed Istanboli, Azza B El-Remessy, Robert W Caldwell, Dennis M Marcus, Ruth B Caldwell
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 50 Issue 10 Pg. 4934-40 (Oct 2009) ISSN: 1552-5783 [Electronic] United States
• PMID: 19098312 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids, Monounsaturated
• Hif1a protein, mouse
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypoxia-Inducible Factor 1, alpha Subunit
• Indoles
• Nitroimidazoles
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Superoxides
• Intercellular Adhesion Molecule-1
• pimonidazole
• Fluvastatin
• Oxygen

Topics

• Animals
• Blotting, Western
• Capillaries
• Disease Models, Animal
• Fatty Acids, Monounsaturated (therapeutic use)
• Fluvastatin
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Immunohistochemistry
• Indoles (therapeutic use)
• Infant, Newborn
• Intercellular Adhesion Molecule-1 (metabolism)
• Lipid Peroxidation
• Mice
• Nitroimidazoles (pharmacology)
• Oxygen (toxicity)
• Phosphorylation
• Retinal Neovascularization (metabolism, pathology, prevention & control)
• Retinal Vessels (pathology)
• Retinopathy of Prematurity (metabolism, pathology, prevention & control)
• STAT3 Transcription Factor (metabolism)
• Superoxides (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)