A small molecular multi-targeting tyrosine kinase inhibitor, anlotinib, inhibits pathological ocular...

Area of Science:

• Ophthalmology
• Pharmacology
• Molecular Biology

Background:

• Ocular neovascularization is a leading cause of blindness, with current treatments having limitations.
• Novel therapeutic strategies are crucial for managing blinding eye diseases.

Purpose of the Study:

• To investigate the therapeutic potential of anlotinib, a small molecule multi-targeting tyrosine kinase inhibitor, in ocular neovascularization.
• To evaluate anlotinib's effects on endothelial cells, pericytes, and animal models of neovascularization.

Main Methods:

• In vitro studies assessed anlotinib's cytotoxicity and its impact on endothelial cell (EC) and pericyte viability, proliferation, migration, and tube formation.
• Western blot analysis examined the inhibition of VEGFR2 and PDGFR-β phosphorylation and downstream signaling.
• In vivo studies utilized oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models.

Main Results:

• Anlotinib demonstrated no cytotoxicity at tested concentrations.
• Anlotinib inhibited EC and pericyte viability, proliferation, migration, and tube formation.
• Anlotinib suppressed VEGFR2 and PDGFR-β phosphorylation and downstream signaling in a dose-dependent manner.
• In vivo, anlotinib reduced avascular areas and neovascular tufts in OIR models.
• Combined anlotinib and Lucentis therapy reduced CNV lesion size and thickness more effectively than Lucentis alone.

Conclusions:

• Anlotinib effectively inhibits key pathways involved in ocular neovascularization.
• Anlotinib demonstrates therapeutic potential in preclinical models of OIR and CNV.
• Anlotinib represents a promising drug candidate for treating ocular neovascularization and preventing blindness.