June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
CD33 regulates the inflammatory response and mitochondrial activity of microglial cells in the rd10 mouse model of retinitis pigmentosa
Author Affiliations & Notes
  • Jing Zhang
    School of Optometry, The Hong Kong Polytechnic University, Hong Kong, Hong Kong
  • Jiang-Mei Wu
    School of Optometry, The Hong Kong Polytechnic University, Hong Kong, Hong Kong
  • Bin Lin
    School of Optometry, The Hong Kong Polytechnic University, Hong Kong, Hong Kong
    Centre for Eye and Vision Research Limited, Hong Kong, Hong Kong
  • Footnotes
    Commercial Relationships   Jing Zhang None; Jiang-Mei Wu None; Bin Lin None
  • Footnotes
    Support  Kindly supported by the Health and Medical Research Fund (HMRF) of Hong Kong Food and Health Bureau, General Research Fund (GRF) from the Hong Kong Research Grants Council, Project of Strategic Importance of The Hong Kong Polytechnic University, Research Centre for SHARP Vision (RCSV) (P0039595) of The Hong Kong Polytechnic University and The Hong Kong Special Administrative Region Government and InnoHK.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2421. doi:
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    • Get Citation

      Jing Zhang, Jiang-Mei Wu, Bin Lin; CD33 regulates the inflammatory response and mitochondrial activity of microglial cells in the rd10 mouse model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2421.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Retinitis pigmentosa (RP) is a group of inherited retinal diseases featured by progressive loss of photoreceptors. Neuroinflammation mediated by microglia participates in the pathophysiology of RP and modulates RP progression. Substantial genetic and functional findings suggest that CD33 (Siglec-3), which is specifically expressed in microglia in the brain, inhibits microglial phagocytosis and the production of proinflammatory cytokines in Alzheimer's disease. However, the functional role of CD33 in regulating neuroinflammation in RP remains unknown.

Methods : We first examined the expression pattern of CD33 in the rd10 mouse model of RP using immunocytochemistry and qRT-PCR. We then generated CD33-/-/rd10 mice by backcrossing CD33 knockout mice (CD33-/-) onto rd10 background and investigated the effect of CD33 deletion on microglia phagocytic activity, production of inflammatory cytokines, photoreceptor survival and visual function. Moreover, we sorted CD11b+CD45+ cells from CD33-/-/rd10 and rd10 retinas (P22) and conducted single-cell RNA-sequencing and bioinformatics analyses. We used BV2 cell line and primary microglial cells with CD33 deficiency to study the cell viability, inflammatory responses, mitochondrial activity, and related signaling pathways in response to LPS stimulation in vitro.

Results : We found that CD33 expression at both mRNA and protein levels was elevated in microglia in the rd10 retinas versus C57BL/6J controls. Deletion of CD33 accelerated microgliosis and photoreceptor degeneration in the rd10 retinas. Single-cell transcriptomic profiling demonstrated significantly increased infiltration of monocytes and alterations in genes related to oxidative phosphorylation, mitochondrial dysfunction, and neuroinflammation. The knockout or silencing of CD33 inhibited the production of pro-inflammatory factors (e.g. IL-1β, TNFα, iNOS) in microglia via regulating the activity of NFκB signaling after LPS stimulation in vitro. In addition, CD33 deficiency improved microglial cell viability and altered mitochondrial activity after LPS stimulation in vitro.

Conclusions : Our study demonstrated that CD33 was involved in the inflammatory response and mitochondrial activity of microglia in rd10 mice. Our findings suggest that CD33 could be a novel therapeutic target for treating chronic inflammation and photoreceptor degeneration in RP.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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