Abstract
Background: Retinal ganglion cell (RGC) degeneration in optic neuropathies is often preceded by neuroinflammatory changes, yet the earliest in vivo indicators of this process remain poorly defined. Vitreous hyperreflective foci (VHRFs) emerging within 24 h following optic nerve crush (ONC) might represent a promising early in vivo indicator of RGC loss. Methods: VHRFs were longitudinally tracked by visible-light optical coherence tomography (vis-OCT) imaging post-ONC. Whole-eye sectioning, immunohistochemistry, and confocal imaging revealed the identity and migration of the VHRFs. RNAscope in situ hybridization detected cytokine mRNA expression, and IL-1 signaling was pharmacologically inhibited by intracameral administration of an IL-1 receptor antagonist: Anakinra post-ONC. Statistical differences between experimental groups were assessed by Student's t-test, one-way and two-way ANOVA. Results: Longitudinal vis-OCT imaging revealed that VHRFs emerged as early as 6 h post-injury and peaked before the significant RGC loss. The VHRFs corresponded to activated amoeboid cells undergoing vertical migration from the outer to inner retina and horizontal movement toward the optic nerve head area. Similar amoeboid cells were also observed in the anterior segment, suggesting a global ocular inflammatory response to the ONC injury. Elevated IL-1β expression was detected in vitreous amoeboid cells, and blockade of IL-1 signaling significantly reduced VHRFs, suppressed microglial migration, and delayed RGC loss. Conclusions: Our findings identify VHRFs as a previously unrecognized early danger signal for RGC degeneration and highlight IL-1–mediated inflammation as a tractable early therapeutic target for preventing RGC degeneration and vision loss.
Recommended Citation
S. Chang and W. Fan and J. Wu and L. Xu and V. A. Lee and C. Zhang and E. P. Kronenberg and W. Xu and H. Yang and H. F. Zhang and X. Liu, "IL-1–mediated Vitreous Inflammation As An Early Indicator Of Retinal Ganglion Cell Loss Following Acute Optic Nerve Injury," Journal of Neuroinflammation, vol. 23, no. 1, article no. 236, BioMed Central, Dec 2026.
The definitive version is available at https://doi.org/10.1186/s12974-026-03860-w
Department(s)
Chemical and Biochemical Engineering
Publication Status
Open Access
Keywords and Phrases
Neuroinflammation; Optic nerve crush; Retinal ganglion cell; Retinal microglia; Visible-light optical coherence tomography; Vitreous hyperreflective foci
International Standard Serial Number (ISSN)
1742-2094
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2026 The Authors, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
01 Dec 2026
PubMed ID
42135831
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biomedical Engineering and Bioengineering Commons, Chemical Engineering Commons
