July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Increased conjunctival monocyte/macrophage antigen presenting cells in Pinkie RXRα deficient mice with accelerated dry eye
Author Affiliations & Notes
  • Stephen C Pflugfelder
    Ophthal-Ocular Surf Ctr, Baylor College of Medicine, Houston, Texas, United States
  • Rodrigo Guimaraes de Souza
    Ophthal-Ocular Surf Ctr, Baylor College of Medicine, Houston, Texas, United States
  • Jehan Alam
    Ophthal-Ocular Surf Ctr, Baylor College of Medicine, Houston, Texas, United States
  • Zhiyuan Yu
    Ophthal-Ocular Surf Ctr, Baylor College of Medicine, Houston, Texas, United States
  • Cintia S De Paiva
    Ophthal-Ocular Surf Ctr, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Stephen Pflugfelder, None; Rodrigo de Souza, None; Jehan Alam, None; Zhiyuan Yu, None; Cintia De Paiva, None
  • Footnotes
    Support  NIH Grant EY11915; Research to Prevent Blindness; William Stamps Farish Fund; Hamill Foundation; Sid W. Richardson Foundation
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1413. doi:
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      Stephen C Pflugfelder, Rodrigo Guimaraes de Souza, Jehan Alam, Zhiyuan Yu, Cintia S De Paiva; Increased conjunctival monocyte/macrophage antigen presenting cells in Pinkie RXRα deficient mice with accelerated dry eye. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1413.

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

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Abstract

Purpose : To compare antigen presenting cell (APC) populations in wild type (WT) control and the Pinkie strain with a loss of function retinoid X receptor alpha (RXRα) mutation and accelerated onset of dry eye disease.

Methods : Naïve female C57BL/6J wild-type (WT) and Pinkie mice aged 6 and 30 weeks were used. Conjunctival goblet cells were counted in PAS-stained sections and Oregon Green dextran staining was used to evaluate corneal barrier disruption. CCL-2 and MHC II stained cells were immunolocalized in conjunctival whole mounts by laser scanning confocal microscopy in 6 and 30-week-old WT and Pinkie mice. Flow cytometry gated on MHCII+ cells was used to phenotype conjunctival APCs.

Results : Compared to WT, Pinkie mice develop significantly greater conjunctival goblet cell loss by 6 weeks and corneal barrier disruption by 30 weeks of age. There is greater immunostaining for the monocyte chemokine CCL-2 in the Pinkie conjunctival epithelium. An increased number of MHC II+ cells were noted in the epithelium and entire conjunctiva in 6-week-old Pinkie. The number of CD11b+F4/80+Ly6C+ (6 and 30 week) and CD11b+F4/80+Ly6C+CD86+ (6 week) macrophages and CD11c+CD11b+F4/80+Ly6C+ (6 and 30 weeks) and CD11c+CD11b+F4/80+Ly6C+CD86+ (6 weeks) dendritic cells (DC) was significantly increased in Pinkie compared to WT mice.

Conclusions : Certain immature and mature macrophage and DC populations increase in the Pinkie conjunctiva, perhaps through CCL-2 mediated chemotaxis. This finding suggests that RXRα may suppress recruitment and maturation of these APCs, maintain immune tolerance and prevent development of dry eye. Additional studies are needed to elucidate the immunomodulatory activity of RXRα in maintaining conjunctival immune tolerance and the relevant RXRα ligands in vivo.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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