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Published on: July 10, 2018
Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice
Muchen Dong1, Guohu Di2, Xiaoping Zhang3
1School 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.
Purpose:
To investigate the effects of subconjunctival bevacizumab injection on the corneal nerve, sensitivity, and epithelial wound healing in mice.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Subconjunctival bevacizumab injection damages corneal nerves and slows healing in mice. Supplementing neurotrophic factors like PEDF, NGF, and CNTF can help restore corneal function.
Area of Science:
- Ophthalmology
- Neuroscience
- Regenerative Medicine
Background:
- Subconjunctival bevacizumab is used to treat ocular conditions.
- Its effects on corneal nerve integrity and healing are not fully understood.
Purpose of the Study:
- To investigate the impact of subconjunctival bevacizumab on corneal nerves, sensitivity, and epithelial wound healing in mice.
- To explore the role of neurotrophic factors in mediating these effects.
Main Methods:
- Mice received subconjunctival injections of varying bevacizumab concentrations.
- Corneal nerve integrity, sensitivity, and epithelial wound healing were assessed.
- Levels of pigment epithelium-derived factor (PEDF), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) were measured.
- The effect of neurotrophic factor supplementation was evaluated.
Main Results:
- Bevacizumab injection led to corneal nerve degeneration, reduced sensitivity, and delayed wound healing, dose-dependently.
- Lower concentrations (1-5 mg/mL) showed gradual recovery.
- Bevacizumab decreased corneal PEDF, NGF, and CNTF levels.
- Exogenous PEDF, NGF, or CNTF attenuated the negative effects of bevacizumab.
Conclusions:
- Subconjunctival bevacizumab impairs corneal innervation, wound healing, and nerve regeneration in mice.
- This impairment may be linked to reduced neurotrophic factor levels.
- Neurotrophic factor supplementation shows potential for mitigating bevacizumab-induced corneal damage.
