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Abstract #126886 Published in IGR 25-2
Loss of monocyte chemoattractant protein-1 reduced monocyte recruitment and preserved retinal ganglion cells in a mouse model of hypertensive glaucoma
Guo M; Schwartz TD; Lawrence ECN; Lu J; Zhong A; Wu J; Sterling JK; Nikonov S; Dunaief JL; Cui QNExperimental Eye Research 2025; 254: 110325
Monocyte chemoattractant protein-1 (MCP-1)/CCL2, a potent chemokine for myeloid cells, has been associated with disease progression in glaucoma. We examined whether genetic knockout (KO) of MCP-1 affected RGC density and function, retinal myeloid cell density, and pro-inflammatory cytokine expression in the setting of microbead induced hypertensive glaucoma. Adult wildtype (WT) C57BL/6J or MCP-1 KO mice received bilateral injections of either magnetic microbeads to elevate intraocular pressure (IOP) or balanced salt solution (BSS) as normotensive controls. After 8 weeks, immunolabeling of retina flat mounts for RBPMS and Iba1 quantified RGC and myeloid soma density in the retina, respectively. Axon density was quantified in optic nerve thin sections, while in vitro multi-electrode array recordings characterized RGC function. Quantitative PCR assessed expression of pro-inflammatory cytokines C1q, IL-1α, and TNF-α in macrophage/microglia-enriched retinal cellular populations. RESULTS: demonstrated lower RGC soma and axon density, and higher myeloid cellular density, in bead vs. BSS-injected eyes of WT mice. In contrast, RGC soma and axon density, as well as myeloid cellular density did not differ between bead and BSS-injected eyes of MCP-1 KO mice. Aspects of RGC firing rates were also preserved in KO compared to WT mice after IOP elevation. Interestingly, expressions of C1q, IL-1α, and TNF-α, cytokines previously shown to be cytotoxic to RGCs, did not differ between WT and KO mice. In summary, genetic ablation of MCP-1 rescued RGCs and decreased myeloid density in the retina without altering pro-inflammatory cytokine expression, supporting a pathogenic role for monocyte recruitment in hypertensive glaucoma.
F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
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