Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice. 2017

Muchen Dong, and Guohu Di, and Xiaoping Zhang, and Qingjun Zhou, and Weiyun Shi
School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, China 2Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.

To investigate the effects of subconjunctival bevacizumab injection on the corneal nerve, sensitivity, and epithelial wound healing in mice. Adult C57BL/6 mice were treated with subconjunctival injection of 1, 2, 5, or 25 mg/mL bevacizumab. The corneal nerve was observed with whole-mount anti-β3-tubulin fluorescence staining. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer. The protein levels of pigment epithelium-derived factor (PEDF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were measured by ELISA. The corneal epithelial wound-healing rate was evaluated by fluorescein staining. The recovery of impaired mouse corneal innervations and epithelial wound-healing rate following bevacizumab injection was evaluated with the co-injection of PEDF, NGF, or CNTF. Subconjunctival bevacizumab injection caused apparent corneal nerve degeneration, attenuated corneal sensitivity, and delayed corneal epithelial wound healing and nerve regeneration in normal mice, which was more significant with increased concentration and times of the bevacizumab injection. However, the corneal nerve and sensitivity gradually improved and recovered in mice with a single injection of 1 to 5 mg/mL bevacizumab. Moreover, the bevacizumab injection significantly decreased the corneal PEDF, NGF, and CNTF content, whereas exogenous PEDF, NGF, or CNTF supplement attenuated impairment of the corneal nerve, sensitivity, and epithelial wound healing after subconjunctival bevacizumab injection. Subconjunctival bevacizumab injection impairs corneal innervations, epithelial wound healing, and nerve regeneration in normal mice, which may be caused by the reduction of neurotrophic factor content in the cornea.

UI MeSH Term Description Entries
D007267 Injections Introduction of substances into the body using a needle and syringe. Injectables,Injectable,Injection
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009416 Nerve Regeneration Renewal or physiological repair of damaged nerve tissue. Nerve Tissue Regeneration,Nervous Tissue Regeneration,Neural Tissue Regeneration,Nerve Tissue Regenerations,Nervous Tissue Regenerations,Neural Tissue Regenerations,Regeneration, Nerve,Regeneration, Nerve Tissue,Regeneration, Nervous Tissue,Regeneration, Neural Tissue,Tissue Regeneration, Nerve,Tissue Regeneration, Nervous,Tissue Regeneration, Neural
D003228 Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Bulbar Conjunctiva,Palpebral Conjunctiva,Plica Semilunaris of Conjunctiva,Plicae Semilunares of Conjunctiva,Tunica Conjunctiva,Conjunctiva, Bulbar,Conjunctiva, Palpebral,Conjunctivas
D003315 Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous CORNEAL EPITHELIUM; BOWMAN MEMBRANE; CORNEAL STROMA; DESCEMET MEMBRANE; and mesenchymal CORNEAL ENDOTHELIUM. It serves as the first refracting medium of the eye. It is structurally continuous with the SCLERA, avascular, receiving its nourishment by permeation through spaces between the lamellae, and is innervated by the ophthalmic division of the TRIGEMINAL NERVE via the ciliary nerves and those of the surrounding conjunctiva which together form plexuses. (Cline et al., Dictionary of Visual Science, 4th ed) Corneas
D003316 Corneal Diseases Diseases of the cornea. Corneal Disease,Disease, Corneal,Diseases, Corneal
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000068258 Bevacizumab An anti-VEGF humanized murine monoclonal antibody. It inhibits VEGF RECEPTORS and helps to prevent PATHOLOGIC ANGIOGENESIS. Avastin,Bevacizumab-awwb,Mvasi,Bevacizumab awwb
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014945 Wound Healing Restoration of integrity to traumatized tissue. Healing, Wound,Healings, Wound,Wound Healings

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