Genome-wide expression differences in anti-Vegf and dexamethasone treatment of inflammatory angiogenesis in the rat cornea.
Pierfrancesco MirabelliAnthony MukwayaAnton LennikovMaria XeroudakiBeatrice PeeboMira SchaupperNeil S LagaliPublished in: Scientific reports (2017)
Angiogenesis as a pathological process in the eye can lead to blindness. In the cornea, suppression of angiogenesis by anti-VEGF treatment is only partially effective while steroids, although effective in treating inflammation and angiogenesis, have broad activity leading to undesirable side effects. In this study, genome-wide expression was investigated in a suture-induced corneal neovascularization model in rats, to investigate factors differentially targeted by dexamethasone and anti-Vegf. Topical treatment with either rat-specific anti-Vegf, dexamethasone, or normal goat IgG (sham) was given to sutured corneas for 48 hours, after which in vivo imaging, tissue processing for RNA microarray, and immunofluorescence were performed. Dexamethasone suppressed limbal vasodilation (P < 0.01) and genes in PI3K-Akt, focal adhesion, and chemokine signaling pathways more effectively than anti-Vegf. The most differentially expressed genes were confirmed by immunofluorescence, qRTPCR and Western blot. Strong suppression of Reg3g and the inflammatory chemokines Ccl2 and Cxcl5 and activation of classical complement pathway factors C1r, C1s, C2, and C3 occurred with dexamethasone treatment, effects absent with anti-Vegf treatment. The genome-wide results obtained in this study provide numerous potential targets for specific blockade of inflammation and angiogenesis in the cornea not addressed by anti-Vegf treatment, as possible alternatives to broad-acting immunosuppressive therapy.
Keyphrases
- vascular endothelial growth factor
- endothelial cells
- genome wide
- oxidative stress
- dna methylation
- low dose
- signaling pathway
- pi k akt
- high resolution
- high glucose
- combination therapy
- clinical trial
- wound healing
- drug delivery
- stem cells
- climate change
- cell death
- binding protein
- diabetic retinopathy
- escherichia coli
- long non coding rna
- transcription factor
- pseudomonas aeruginosa
- epithelial mesenchymal transition
- optical coherence tomography
- photodynamic therapy
- mesenchymal stem cells
- diabetic rats
- induced apoptosis
- single molecule