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Microglia Regulate Neuroglia Remodeling in Various Ocular and Retinal Injuries

Paschalis, Eleftherios I, Lei, Fengyang, Zhou, Chengxin, Chen, Xiaohong Nancy, Kapoulea, Vassiliki, Hui, Pui-Chuen, Dana, Reza, Chodosh, James, Vavvas, Demetrios G, Dohlman, Claes H·2019·The Journal of Immunology
DOI 10.4049/jimmunol.1800982PMC PMC6325007

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Abstract

Reactive microglia and infiltrating peripheral monocytes have been implicated in many neurodegenerative diseases of the retina and CNS. However, their specific contribution in retinal degeneration remains unclear. We recently showed that peripheral monocytes that infiltrate the retina after ocular injury in mice become permanently engrafted into the tissue, establishing a proinflammatory phenotype that promotes neurodegeneration. In this study, we show that microglia regulate the process of neuroglia remodeling during ocular injury, and their depletion results in marked upregulation of inflammatory markers, such as Il17f, Tnfsf11, Ccl4, Il1a, Ccr2, Il4, Il5, and Csf2 in the retina, and abnormal engraftment of peripheral CCR2+ CX3CR1+ monocytes into the retina, which is associated with increased retinal ganglion cell loss, retinal nerve fiber layer thinning, and pigmentation onto the retinal surface. Furthermore, we show that other types of ocular injuries, such as penetrating corneal trauma and ocular hypertension also cause similar changes. However, optic nerve crush injury–mediated retinal ganglion cell loss evokes neither peripheral monocyte response in the retina nor pigmentation, although peripheral CX3CR1+ and CCR2+ monocytes infiltrate the optic nerve injury site and remain present for months. Our study suggests that microglia are key regulators of peripheral monocyte infiltration and retinal pigment epithelium migration, and their depletion results in abnormal neuroglia remodeling that exacerbates neuroretinal tissue damage. This mechanism of retinal damage through neuroglia remodeling may be clinically important for the treatment of patients with ocular injuries, including surgical traumas.

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Metadata

Authors
Paschalis, E. I., Lei, F., Zhou, C., Chen, X. N., Kapoulea, V., Hui, P.-C., Dana, R., Chodosh, J., Vavvas, D. G., & Dohlman, C. H.
Affiliations
Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School , Boston, MA 02114
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2019-01
Volume
202
Issue
2
Pages
539-549
ISSN
  • 0022-1767
  • 1550-6606
DOI
10.4049/jimmunol.1800982
PMC
PMC6325007
Cited by
50
References
7
Language
en
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)

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CoChat. (2026). Citation check: Microglia Regulate Neuroglia Remodeling in Various Ocular and Retinal Injuries. https://app.cochat.ai/papers/10.4049/jimmunol.1800982
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Paschalis, E. I., Lei, F., Zhou, C., Chen, X. N., Kapoulea, V., Hui, P.-C., Dana, R., Chodosh, J., Vavvas, D. G., & Dohlman, C. H. (2019). Microglia Regulate Neuroglia Remodeling in Various Ocular and Retinal Injuries. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1800982

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