| First Author | Lavine JA | Year | 2017 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 58 |
| Issue | 1 | Pages | 299-308 |
| PubMed ID | 28114591 | Mgi Jnum | J:254675 |
| Mgi Id | MGI:6112217 | Doi | 10.1167/iovs.16-20204 |
| Citation | Lavine JA, et al. (2017) beta2-Adrenergic Receptor Antagonism Attenuates CNV Through Inhibition of VEGF and IL-6 Expression. Invest Ophthalmol Vis Sci 58(1):299-308 |
| abstractText | Purpose: The role of beta-adrenergic receptor (AR) signaling in neovascular ocular diseases has recently emerged. We have previously reported that intraperitoneal propranolol inhibits choroidal neovascularization (CNV) in vivo and beta2-AR blockade reduces vascular endothelial growth factor (VEGF) expression in mouse retinal pigment epithelium and choroidal endothelial cells in culture. Here we tested the hypothesis that the beta2-AR regulates CNV through modulation of VEGF and inflammatory cytokine expression. Methods: Mice were subjected to laser burns, inducing CNV, and were treated with an intravitreal beta2-AR antagonist. After 3 and 5 days, total eye interleukin-6 (IL-6) and VEGF protein levels were measured, respectively. After 14 days, CNV was measured on choroidal-scleral flatmounts. The effects of beta-AR signaling on VEGF and IL-6 expression were investigated in various mouse retinal and human RPE cells by using specific beta-AR agonists and antagonists. Results: beta2-Adrenergic receptor signaling increased Vegf mRNA expression by approximately 3- to 4-fold in mouse retinal microglia and pericytes in culture. beta2-Adrenergic receptor signaling upregulated IL-6 mRNA expression between 10- and 60-fold in mouse retinal microglia, pericytes, RPE, and choroidal endothelial cells in culture. Intravitreal injection of beta2-AR antagonist ICI 118,551 reduced CNV by 35% and decreased IL-6 protein levels by approximately 50%. In primary human RPE cells, beta2-AR activation also stimulated VEGF and IL-6 mRNA expression by 2- and 10-fold, respectively. Conclusions: Anti-VEGF therapy for CNV is highly effective; however, some patients are resistant to therapy while others undergo repeated, frequent treatments. beta2-Adrenergic receptor signaling is a potential therapeutic target because of its angiogenic and inflammatory properties. |
