June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Microglia utilize both CR3 and Mertk receptor pathways to eliminate RGCs in the embryonic retina
Author Affiliations & Notes
  • Navita Lopez
    Neurobiology, University of Utah Health, Salt Lake City, Utah, United States
  • Sarah R Anderson
    Neurobiology, University of Utah Health, Salt Lake City, Utah, United States
  • Monica L Vetter
    Neurobiology, University of Utah Health, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Navita Lopez None; Sarah Anderson None; Monica Vetter Roche, Code C (Consultant/Contractor)
  • Footnotes
    Support  NIH Grant EY02423 to NL, EY031096 and EY030307 to MLV
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1352 – F0283. doi:
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    • Get Citation

      Navita Lopez, Sarah R Anderson, Monica L Vetter; Microglia utilize both CR3 and Mertk receptor pathways to eliminate RGCs in the embryonic retina. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1352 – F0283.

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

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Abstract

Purpose : Microglia are the resident myeloid cells of the CNS that serve multiple roles during development. We previously showed that these phagocytes are responsible for the elimination of a subset of newborn retinal ganglion cells (RGCs) in the embryonic retina. This is partly dependent on microglial recognition of RGCs by complement receptor 3 (CR3); however, we hypothesize that additional receptor pathways are involved. Here we investigate the role of the TAM receptor tyrosine kinases, which are known to facilitate phagocytosis. Embryonic retinal microglia express two members of this family, Mertk and Axl. Microglial-mediated phagocytosis of excess neurons is a pivotal process in neural development, and we hypothesize that embryonic retinal microglia utilize both CR3 and TAM receptors to recognize and eliminate a subset of viable newborn RGCs in the developing retina and regulate RGC density.

Methods : We used B6. Mertk-/-, Axl-/- and Mertk-/-Axl-/- mice to assess the role of TAM receptors in embryonic RGC elimination. Retinal whole mounts were collected at P0, when excess RGCs would persist, and we performed RBPMS immunostaining and confocal imaging then quantified RGC density. To determine if multiple receptor pathways cooperate to contribute to embryonic RGC elimination, we used Mertk-/-, CD11b-/- (CR3) and Mertk-/- CD11b-/- mice and analyzed RGC number at P0 in whole mount retinas.

Results : We find that genetic ablation of Mertk resulted in an increase in RGC density at birth compared to wildtype controls. Mertk-/- mice showed an 8.95% increase in RGC density at P0 (n=12; p=0.005). Mice deficient in both Mertk and Axl, resulted in a 11.81% increase in RGC density (n=12; p<0.0001), similar to Mertk-/- alone, suggesting that Mertk is primarily responsible. We show that with knockout of both Mertk and CD11b, there is an additive effect, with a 19.78% increase in RGC density (n=4; p<0.0001).

Conclusions : Shortly after RGCs are generated, a non-apoptotic subset is eliminated by phagocytic microglia. We show that multiple microglial receptor pathways contribute to the embryonic elimination of RGCs, and we establish that Mertk and CR3 cooperate in this process. Future studies will define the properties of RGCs targeted for elimination.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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