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. 2023 Sep 18;16(9):1450-1455.
doi: 10.18240/ijo.2023.09.11. eCollection 2023.

Effect of a novel tyrosine kinase inhibitor nintedanib on bFGF and VEGF concentrations in a rabbit retinal vein occlusion model

Wei Fang  1 , Jing Zhai  1 , Zhen-Bin Qian  1 , Hai-Dong Li  1 , Meng-Di Wang  1 , Li-Jun Shen  1
Affiliations

Effect of a novel tyrosine kinase inhibitor nintedanib on bFGF and VEGF concentrations in a rabbit retinal vein occlusion model

Wei Fang et al. Int J Ophthalmol. .

Abstract

Aim: To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) simultaneously for retinal vascular disease in vivo.

Methods: After a laser induced rabbit retinal vein occlusion (RVO) model was made, 0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control. Intracameral samples were taken on the day before laser treatment and days 1, 3, 7, 14, 21, and 28 after treatment. Enzyme-linked immunosorbent assay (ELISA) was used to test the bFGF and VEGF-A concentrations in the aqueous humor.

Results: Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes. In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day. After nintadanib injection in the study eye, both bFGF and VEGF-A showed a significant reduction on the 4th day (7th day after laser treatment) when compared to the control eye, and kept on low level in the following several weeks.

Conclusion: Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent, which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases.

Keywords: basic fibroblast growth factor; nintedanib; rabbit model; retinal vein occlusion; tyrosine kinase inhibitor; vascular endothelial growth factor.

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Figures

Figure 1
Figure 1. Rabbit retinal vein occlusion model
Rabbit retinal vein occlusion model was induced by 810 nm solid infrared laser that was enhanced by indocyanine green dye. The arrows indicated the occluded retinal vein immediately after laser delivery.
Figure 2
Figure 2. Nintedanib preparation for intravitreal injection
Nintedanib suspension was prepared from oral capsules. A capsule of 150 mg nintedanib was dissolved in 30 mL saline solution with a concentration of 5 mg/mL. A dose of 0.1 mL (0.5mg) nintedanib was used for intravitreal injection.
Figure 3
Figure 3. Trend analysis of basic fibroblast growth factor (bFGF) in the two eyes of rabbit models
A: bFGF concentration trend on the sampling days in the control eyes (OD); B: bFGF concentration trend in the study eyes (OS), in which nintedanib was injected on the day 3; C: Comparison between the study eyes and the contralateral eyes.
Figure 4
Figure 4. Trend analysis of vascular endothelial growth factor-A (VEGF-A) in the two eyes of rabbit models
A: VEGF-A concentration trend on the sampling days in the control eyes (OD); B: VEGF-A concentration trend in the study eyes (OS), in which nintedanib was injected on the 3rd day; C: Comparison between the study eyes and the contralateral eyes.
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