A Subretinal Matrigel Rat Choroidal Neovascularization (CNV) Model and Inhibition of CNV and Associated Inflammation and Fibrosis by VEGF Trap

Abstract

The subretinal Matrigel CNV model provides a convenient tool for the study of the diverse components of complex CNV lesions. The data not only confirm the critical roles of VEGF in the development and maintenance of CNV, but further demonstrate that VEGF and other VEGF receptor 1 ligands promote CNV-associated inflammation and fibrosis.

Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial

“…DEX implant) that would allow reduced frequency of ranibizumab injections may be associated with improved safety in large patient populations. As inflammatory cells associated with CNV tissue may induce CNV and stimulate other pathologic processes, such as fibrosis, that lead to vision loss in nvAMD [8,9,10], immunologic effects of high initial steroid concentrations following DEX implant administration, such as leukocyte apoptosis [22,23,24,50], may account for the beneficial effect of DEX implant observed in this study.…”

“…CNV tissue consists of blood vessels, inflammatory cells, and mesenchymal cells within a loose extracellular matrix [7]. Subretinal leakage, hemorrhage, and fluid accumulation can lead to rapid vision loss, but nonvascular components of the disease process, such as inflammation and fibrosis, are also believed to contribute to disease progression [8,9,10]. Inflammatory involvement has been demonstrated in studies of excised CNV tissue of nvAMD patients.…”

The Effect of AMA0428, a Novel and Potent ROCK Inhibitor, in a Model of Neovascular Age-Related Macular Degeneration

“…Inhibiting the initial inflammatory process and the subsequent angiogenesis might also indirectly decrease fibrosis, the final stage of CNV. Cao et al 82 already demonstrated that VEGF Trap, an inhibitor of VEGF and PlGF, was able to prevent fibrosis associated with CNV, 82 due to its inhibition of leukocyte infiltration and angiogenesis. Acting on the inflammatory process to block collagen deposition is of utmost importance, as proinflammatory factors contribute to the development of experimental CNV and are present in human CNV fibrotic membranes.…”

Ras pathway inhibition prevents neovascularization by repressing endothelial cell sprouting

“…The values obtained from each mouse for each different α-miR-132 is more effective than VEGF-trap. VEGF-trap, a fusion protein of IgG Fc fragments and VEGFR1/VEGFR2, has been shown to reduce tuft formation in animal models of OIR and laser-induced choroidal neovascularization (CNV) (23)(24)(25) and in patients with age-related macular degeneration with CNV (26,27). We developed a VEGF-trap mimetic and tested its activity at several doses (Supplemental Figure 7A) and also directly compared its angiostatic activity with that of commercially available aflibercept (Eylea or VEGF-trap Eye) in both the OIR and laser-induced CNV models.…”