Dendritic cells play no significant role in the laser-induced choroidal neovascularization model

Steven Droho; Harris Perlman; Jeremy A. Lavine

doi:10.1038/s41598-021-96704-x

Dendritic cells play no significant role in the laser-induced choroidal neovascularization model

Steven Droho, Harris Perlman, Jeremy A. Lavine^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Age-related macular degeneration (AMD) is genetically associated with complement. Dendritic cells (DCs) play key roles during innate and adaptive immunity, and express complement components and their receptors. We investigated ocular DC heterogeneity and the role of DCs in the laser-induced choroidal neovascularization (CNV) model. In order to determine the function of DCs, we used two models of DC deficiency: the Flt3^−/− and Flt3l^−/− mouse. We identified three types of ocular DCs: plasmacytoid DC, classical DC-1, and classical DC-2. At steady-state, classical DCs were found in the iris and choroid but were not detectable in the retina. Plasmacytoid DCs existed at very low levels in iris, choroid, and retina. After laser injury, the number of each DC subset was up-regulated in the choroid and retina. In Flt3^−/− mice, we found reduced numbers of classical DCs at steady-state, but each DC subset equally increased after laser injury between wildtype and Flt3^−/− mice. In Flt3l^−/− mice, each DC subsets was severely reduced after laser injury. Neither Flt3^−/− or Flt3l^−/− mice demonstrated reduced CNV area compared to wildtype mice. DCs do not play any significant role during the laser-induced CNV model of neovascular AMD.

Original language	English (US)
Article number	17254
Journal	Scientific reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-96704-x
State	Published - Dec 2021

Funding

We thank Kenneth M. Murphy for generously providing the Flt3−/− and Flt3l−/− mice. HP was supported by NIH Grant AR064546, HL134375, AG049665, UH2AR067687, the United States-Israel Binational Science Foundation (2013247), and the Rheumatology Research Foundation (Agmt 05/06/14). HP was also supported by the Mabel Greene Myers Professor of Medicine and generous donations to the Rheumatology Precision Medicine Fund. JAL was supported by NIH grant K08 EY030923, the Research to Prevent Blindness Sybil B. Harrington Career Development Award for Macular Degeneration, and the Illinois Society for the Prevention of Blindness. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. This study was supported by an Unrestricted Departmental Grant from Research to Prevent Blindness. No funding body had any role in the design of the study, collection, analysis, interpretation of data, or in writing the manuscript.

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title = "Dendritic cells play no significant role in the laser-induced choroidal neovascularization model",

abstract = "Age-related macular degeneration (AMD) is genetically associated with complement. Dendritic cells (DCs) play key roles during innate and adaptive immunity, and express complement components and their receptors. We investigated ocular DC heterogeneity and the role of DCs in the laser-induced choroidal neovascularization (CNV) model. In order to determine the function of DCs, we used two models of DC deficiency: the Flt3−/− and Flt3l−/− mouse. We identified three types of ocular DCs: plasmacytoid DC, classical DC-1, and classical DC-2. At steady-state, classical DCs were found in the iris and choroid but were not detectable in the retina. Plasmacytoid DCs existed at very low levels in iris, choroid, and retina. After laser injury, the number of each DC subset was up-regulated in the choroid and retina. In Flt3−/− mice, we found reduced numbers of classical DCs at steady-state, but each DC subset equally increased after laser injury between wildtype and Flt3−/− mice. In Flt3l−/− mice, each DC subsets was severely reduced after laser injury. Neither Flt3−/− or Flt3l−/− mice demonstrated reduced CNV area compared to wildtype mice. DCs do not play any significant role during the laser-induced CNV model of neovascular AMD.",

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Dendritic cells play no significant role in the laser-induced choroidal neovascularization model

Abstract

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