Experimental Eye Research, cilt.270, 2026 (SCI-Expanded, Scopus)
Background: To evaluate the efficacy and safety of intravitreal injection of the multityrosine kinase inhibitor nintedanib (NTB) in a mouse model of proliferative vitreoretinopathy (PVR) induced by dispase. Methods: Fifty-two male C57BL/6 mice received intravitreal injections in the right eye and were divided into four groups: PVR, PVR + NTB, NTB-only, and vehicle. Uninjected contralateral eyes served as a healthy-control group. The PVR and PVR + NTB groups were compared based on clinical and histopathological PVR grading. Immunohistochemistry, ELISA, RT-PCR, and Western blot analyses were used to evaluate and compare markers of inflammation, fibrogenesis, and epithelial-mesenchymal transition between PVR, PVR + NTB, and healthy-control groups. Potential retinal toxicity was assessed using electroretinography and histopathology in the NTB-only and vehicle groups. Results: Clinical PVR grades were significantly lower in the PVR + NTB group (0.65 ± 0.93) than in the PVR group (2.70 ± 1.75) (p < 0.001). Histopathological grading was also significantly lower in the PVR + NTB group (1.62 ± 0.91) compared with the PVR group (3.87 ± 1.24) (p = 0.002). Compared with the PVR group, IL-6, PDGF, TGF-β, and TNF-α levels, as well as acta-2, col1a1, and fn-1 mRNA expression were significantly lower in the PVR + NTB group. Phosphorylated-PDGFR-α levels were also reduced, whereas PDGFR-α protein expression remained unchanged. No signs of retinal toxicity were observed in electroretinography or histopathology. Conclusions: In this mouse PVR model, intravitreal NTB reduced clinical, histopathological, and biochemical manifestations of PVR without detectable toxicity. Intravitreal NTB may represent a promising therapeutic option for the management of PVR.