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| Transient Depletion of Microglia Attenuates Light-Induced Retinal Degeneration in Mice |
| Bilin Rao, Jiayi Xiao, Xin Lin, Keduo Zang, Hang Tan, Chun Tang, Jun Zhang, Meiling Gao |
Laboratory of Retinal Physiology and Disease, School of Ophthalmology & Optometry and Eye Hospital,Wenzhou Medical University, The State Key Laboratory of Optometry and Vision Science, Wenzhou325027, China |
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Abstract Objective: To investigate the protective effect of microglia on acutely light-induced retinal degeneration
in the mouse. Methods: This was an animal experimental study. Thirty male ICR mice were randomly
divided into a control group, light-damaged group and a microglia depletion group. The control group did
not receive any treatment. The light-damaged group was exposed to 15 000 lx white light for 20 hours. The
microglia depletion group was intraperitoneally injected with the small molecule inhibitor PLX5622 for 5
days before white light irradiation, followed by 15 000 lx white light irradiation for 20 hours, and then the
PLX5622 injection was continued for 3 more days. Retinal function was measured by the electroretinogram
on day 5 after light exposure. Then the eyes were removed, and the eye cup or whole-mount retina was
prepared. Immunohistochemistry and TUNEL staining were used to observe the degree of retinal damage
and the morphology and function of microglia. The experimental data were analyzed by one-way analysis
of variance (ANOVA). Results: In this study, mice were exposed to 15 000 lx white light for 20 hours to
obtain a stable model of retinal dysfunction and photoreceptor apoptosis. The amplitudes of the a and b
waves of the ERG response showed that photoreceptors and bipolar cells were dysfunctional in the
lightdamaged group, and TUNEL positive cells increased significantly compared to the control group (P=0.035).
Activated microglia also increased significantly (P<0.001). Immunohistochemical results showed that
microglias in the outer nuclear layer and outer plexiform layer were significantly reduced in the microglia
depletion group compared to the light-damaged group (P=0.027). The CtBP2 signal and PKC-α signal
were enhanced, and the outer segment length remained at a normal level (P<0.001), but there was no
statistically significant differences between the ERG response b wave amplitude and TUNEL positive cells.
Conclusion: The depletion of microglia can reduce photoreceptor apoptosis and save retinal function in the
very short term.
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Received: 09 August 2020
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| Fund: National Key R&D Program of China (Light Health) (2017YFB0403700); National
Natural Science Foundation of China (82070981); Natural Science Foundation of Zhejiang Province
(LY22H120008); Wenzhou Natural Science Foundation of China (ZX-Y20190168); Service Technology Innovation Project of Wenzhou Association for Science and Technology (kjfw24); The Start-Up Foundation of Wenzhou Medical University (89219003) |
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Corresponding Authors:
Meiling Gao, Laboratory of Retinal Physiology and Disease, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, The State Key Laboratory of Optometry and Vision Science, Wenzhou 325027, China (Email: gaoml@wmu.edu.cn)
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