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Identifying VEGF‐independent factors for targeted antiangiogenic therapy in the cornea
Author(s) -
Lagali N.,
Mukwaya A.,
Mirabelli P.,
Jensen L.,
Xeroudaki M.,
Ali Z.,
Peebo B.
Publication year - 2016
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2016.0036
Subject(s) - angiogenesis , corneal neovascularization , neovascularization , dexamethasone , medicine , in vivo , transcriptome , cancer research , vegf receptors , cornea , vascular endothelial growth factor a , vascular endothelial growth factor , microarray analysis techniques , bioinformatics , gene expression , biology , gene , ophthalmology , genetics
Summary Purpose To identify prospective inhibitors of inflammatory angiogenesis that operate largely independent of the VEGF pathway. Methods Inflammatory angiogenesis was induced in the murine cornea using surgical sutures. Thereafter separate experiments were conducted to (i) prevent neovascularization in an early phase by steroid (dexamethasone) or anti‐VEGFA therapy, and (ii) regress existing neovessels by removal of the initial stimulus. Phenotypic changes were examined by in vivo corneal imaging, whole‐transcriptome expression analysis was performed by comparative bioinformatics analysis of gene microarray data, and expression of target genes of interest was confirmed by RT‐PCR. Results Steroid treatment halted initial angiogenic sprouting while anti‐VEGF therapy was less effective. Steroids targeted key inflammatory and angiogenic pathways largely unaffected by anti‐VEGF treatment. Interestingly, several key inflammatory and angiogenic pathways unrelated to VEGF were suppressed during natural angiogenic regression while endogenous inhibitors of angiogenesis were activated. Conclusion The identified factors may represent novel therapeutic targets for possible mono‐ or combination therapy with anti‐VEGF agents to improve efficacy.