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Updated: Jun 13, 2025
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Nintedanib inhibits neovascularization and subretinal fibrosis in a laser-induced choroidal neovascularization mouse
Shiyue Qin1, Yingying Zhu2, Yinping Liu3
1Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu Province, China; Department of Ophthalmology, Taizhou People's Hospital, No. 366 Taihu Road, Taizhou, 225300, Jiangsu Province, China.
Background:
Subretinal fibrosis is a pivotal pathological factor contributing to vision loss in the elderly with neovascular age-related macular degeneration (nAMD), which is lack of effective treatment currently. The aim of this study was to assess the effects of nintedanib on subretinal fibrosis in a laser-induced choroidal neovascularization (CNV) mouse model and elucidate the molecular mechanisms of its action.
Methods:
The CNV mouse model was established by laser photocoagulation, and nintedanib was administered intravitreally 1 day after laser induction to verify the therapeutic efficacy of nintedanib on mice. TGF-β1 was employed to induce epithelial-mesenchymal transition (EMT) in ARPE-19 cells. Subsequently, immunofluorescence, transwell migration, scratch assay and Western blot were employed to assess the effect of nintedanib on subretinal fibrosis, EMT and EMT-associated cell function.
Results:
The neovascular and fibrotic lesions exhibited a significant reduction in laser-induced CNV mice on days 7 and 14 after intravitreal injection of various concentrations of nintedanib. Compared to normal control mice, the expression of fibrosis markers (collagen-1, α-SMA and fibronectin) was significantly upregulated in the RPE-choroid-sclera complexes of CNV mice, which was effectively attenuated by nintedanib. Furthermore, following nintedanib treatment, the TGF-β1-induced EMT of the ARPE-19 cells was significantly inhibited, as evidenced by a reduction in the levels of collagen-1, α-SMA, fibronectin, Vimentin and N-cadherin, along with a diminished capacity for cell migration. Mechanistically, nintedanib effectively blocked the activation of Smad 2/3, ERK 1/2, p38 and Akt signaling pathways in ARPE-19 cells induced by TGF-β1.
Conclusion:
The inhibition of subretinal fibrosis by nintedanib might be attributed to its suppression of EMT via inactivation of the Smad 2/3, ERK 1/2, p38 and Akt signaling pathways, thereby providing a potential molecule for the treatment of subretinal fibrosis.
