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Purpose: To evaluate the effect of intraocularly applied epidermal growth factor receptor (EGFR) antibody panitumumab on axial elongation.
Methods: This is a preclinical, safety, and efficacy experimental study. Guinea pigs aged 2-3 weeks were fitted with bilateral plano lenses (Group I; n = 10) or underwent bilateral lens-induced myopization (LIM) (Group II; n = 10) with no intravitreal injections. Animals with LIM of Groups III (n = 15), IV (n = 15) and V (n = 15) received three 4-weekly intravitreal injections of panitumumab at doses of 25, 50 and 100 μg, respectively, into their right eyes, and of phosphate-buffered saline into their left eyes.
Results: Inter-eye differences in axial elongation (right eye minus left eye at study end) decreased (p < 0.001) from 0.00 ± 0.02 mm (Group I) and - 0.01 ± 0.02 mm (Group II) to -0.09 ± 0.03 mm (Group III), -0.12 ± 0.03 mm (Group IV) and - 0.17 ± 0.05 mm (Group V). Interocular choroidal thickness differences (measured by optical coherence tomography) increased (p < 0.01) from Groups I and II to Groups III-V. Western blot analysis showed an increase (p < 0.05) in expression levels of EGFR and its downstream phosphorylated signalling molecule, p-PI3K, in Group II compared to Group I and a decrease in Groups III-V compared to Group II (all p < 0.01). Interocular differences in retinal thickness did not differ significantly (p > 0.05) between the groups. TUNEL staining revealed no significant differences in retinal apoptotic cell density among any groups (all p > 0.05).
Conclusions: Intravitreally administered panitumumab in young guinea pigs with LIM resulted in a dose-dependent and treatment frequency-dependent reduction in axial elongation, supporting the role of EGFR signalling in axial elongation.
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http://dx.doi.org/10.1111/aos.17516 | DOI Listing |
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Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Research Center of the Basic Discipline of Cell Biology, Hebei Collaboration Innovation Center for Cell Signaling and Environmental Adaptation, Hebei Key Laboratory of Molecular and Cellular Biology, College of Life Scienc
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Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:
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Animal Cancer Care and Research Program, University of Minnesota, St Paul, Minnesota; Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Center for Immunology
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Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, 11794, USA.
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