CM082 suppresses hypoxia-induced retinal neovascularization in larval zebrafish

TL;DR

CM082, an oral drug, reduces harmful blood vessel growth in the eyes of zebrafish larvae under low oxygen conditions, offering a non-invasive treatment option for eye diseases.

Contribution

CM082 is shown to be a non-invasive, orally administered tyrosine kinase inhibitor effective against retinal neovascularization.

Findings

CM082 suppressed retinal neovascularization in zebrafish larvae under hypoxia.

The drug rescued retinal ganglion cell loss and visual function.

CM082's effect was linked to Vegfr2 phosphorylation inhibition.

Abstract

Retinal neovascularization is a common feature of several ocular neovascular diseases, which are the leading cause of blindness in the world. Current treatments are administered through invasive intravitreal injections, leading to poor patient compliance, serious ocular complications and heavy economic burdens. Thus, an alternative less or non-invasive therapeutic strategy is in demand. Here, a non-invasive oral tyrosine kinase inhibitor, CM082, was evaluated in a retinal neovascularization model induced by hypoxia in zebrafish larvae. We found that CM082 effectively suppressed retinal neovascularization, rescued cell loss in the retinal ganglion cell layer, and rescued the visual function deficiency. Our results elucidated that CM082 mediated its therapeutic efficacy primarily through the inhibition of Vegfr2 phosphorylation. The findings demonstrated that CM082 possessed strong antiangiogenic effects and may serve as a potential treatment for angiogenesis in ocular neovascular diseases.

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