Caveolin-1 expression regulates blood-retinal barrier permeability and retinal neovascularization in oxygen-induced retinopathy.

BACKGROUND

Caveolin-1 expression correlates with the permeability of endothelial barriers and angiogenesis. However, the role of caveolin-1 in retinal neovascularization remains unknown. We evaluated the effect of caveolin-1 on the blood-retina barrier and retinal neovascularization in a murine model of oxygen-induced retinopathy.

METHODS

Starting at postnatal day 7, mice were exposed to 75 ± 5% oxygen for 5 days and then returned to room air conditions to induce retinal neovascularization. Effects on blood-retina barrier were evaluated by Western blot analysis of extravasated albumin in the retina. Retinal neovascularization morphology was studied by fluorescence angiography and was quantified by counts of the endothelial nuclei that protruded into the vitreous cavity. Reverse transcription-polymerase chain reaction and Western blot analysis was used to examine retinal expression levels of caveolin-1. siRNA against caveolin-1 was injected intravitreally in the oxygen-induced retinopathy models. Effects on caveolin-1 mRNA and protein, and retinal neovascularization were assessed as described above.

RESULTS

Caveolin-1 expression was found to increase during hypoxia and overexpression of caveolin-1 correlated with the appearance of extravascular albumin. Caveolin-1 siRNA reduced caveolin-1 mRNA and protein levels by 47.94% and 54.76%, respectively. Furthermore, caveolin-1 siRNA inhibition reduced retinal neovascularization by 51.3% and reduced albumin leakage by 56.32%.

CONCLUSIONS

Caveolin-1 may play an important role in induction of retinal neovascularization. SiRNA against caveolin-1 can inhibit experimental retinal hyperpermeability and neovascularization. Therefore, the inhibition of caveolin-1 may be a powerful and novel therapeutic tool for the treatment of ischaemia-induced retinal diseases.