Title:Anti-vascular Endothelial Growth Factor Antibody Limits the Vascular Leakage and Decreases Subretinal Fibrosis in a Cynomolgus Monkey Choroidal Neovascularization Model
VOLUME: 17 ISSUE: 4
Author(s):Satoshi Inagaki, Masamitsu Shimazawa*, Koji Hamaguchi, Wataru Otsu, Tomoaki Araki, Yuji Sasaki, Yosuke Numata, Hideshi Tsusaki and Hideaki Hara
Affiliation:Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories (SNBL DSR), Kagoshima, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories (SNBL DSR), Kagoshima, Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories (SNBL DSR), Kagoshima, Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories (SNBL DSR), Kagoshima, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu
Keywords:Anti-VEGF therapy, choroidal neovascularization, cynomolgus monkey, fibrosis, Age-related macular
degeneration, fibrotic scarring.
Abstract:
Objective: This study was conducted to evaluate the effects of anti-vascular endothelial
growth factor (VEGF) antibody (bevacizumab) on vascular leakage and fibrosis in a monkey
choroidal neovascularization (CNV) model. The relationship between fibrotic tissue and subretinal
hyper-reflective material (SHRM), in optical coherence tomography (OCT) images, was also investigated.
Methods: Experimental CNV was induced in male cynomolgus monkeys by laser photocoagulation.
Intravitreal injection of bevacizumab at 0.5 mg/eye/dosing was initiated 2 weeks before or after laser
irradiation and thereafter, conducted intermittently at 2- or 3-week intervals. Fluorescein fundus angiography
(FA) and OCT imaging were conducted weekly from 2 to 7 weeks after laser irradiation.
CNV leakage was evaluated by an established grading method using FA images. To assess the fibrosis
and scarring, Masson’s trichrome specimens of each CNV lesion were prepared, and morphometric
analysis was conducted using an image analysis software.
Results: The effects of bevacizumab on vascular leakage were shown using an established evaluation
method. Morphometric analysis of Masson’s trichrome-stained (MT) specimens revealed that
collagen fiber synthesis was suppressed by bevacizumab pre-treatment (-29.2%) or post-treatment
(-19.2%). SHRM was detected in OCT images in a monkey CNV model, and a significant correlation
between the SHRM area in the OCT images and the collagen fiber area in the MT specimens
was noted.
Conclusion: In the established cynomolgus monkey CNV model, bevacizumab prevented blood
leakage but could not completely suppress fibrosis. SHRM in the OCT images reflected retinal
fibrous tissue in a laser-induced CNV monkey model. This model might be useful for elucidating the
pathology and development therapy for neovascularization or fibrosis.
