Abstract
Purpose::
Recent studies have demonstrated that endothelial progenitor cells (EPCs) were recruited to the retina and contributed to the retinal and choroidal neovascularization in a murine model. Interestingly, it has also been shown that the protease cathepsin L has a critical role for EPC-mediated neovascularization (C Urbich, Nat Med 2004). To offer a novel therapeutic strategy targeting EPCs, we examined whether retinal and choroidal neovasucularization were decreased by inhibition of cathepsin L.
Methods::
Mice with oxygen-induced ischemic retinopathy (OIR) or with choroidal neovascularization (CNV) received periocular injection of cathepsin L inhibitor or vehicle only. Mice with OIR were sacrificed at P17 and mice with CNV were sacrificed 2 weeks after laser irradiation. Serial sections were made from the eyeball and the area of neovascularization was analyzed using image analysis software.
Results::
In OIR, mice treated with 400 µM or 40 µM cathepsin L inhibitor had significantly less retinal neovascularization than did vehicle-treated mice (49.6% and 26.0% of vehicle-treated mice (P<0.01)). In CNV model, mice treated with 400 µM or 40 µM cathepsin L inhibitor also had significantly less CNV than did vehicle-treated mice (40.8% and 21.1% of vehicle-treated mice (P<0.01)).
Conclusions::
Inhibition of cathepsin L causes a reduced neovascularization in OIR and CNV model. The results suggest that cathepsin L plays a critical role in the development of retinal and choroidal neovascularization, and cathepsin L might be a novel therapeutic target for intraocular pathological neovascularization.
Keywords: neovascularization • retinal neovascularization • choroid: neovascularization