Retinoid Regulation of Ocular Surface Innate Inflammation.
Jehan AlamZhiyuan YuCintia S De PaivaStephen C PflugfelderPublished in: International journal of molecular sciences (2021)
Corneal and conjunctival inflammation and dry eye develop in systemic vitamin A deficiency (VAD). The objective of this study was to investigate the lacrimal ocular surface retinoid axis, particularly immunomodulatory effects of retinoic acid (RA) and change in conjunctival myeloid cell number and phenotype in VAD. We discovered that ocular surface epithelial and myeloid cells express retinoid receptors. Both all trans- and 9-cis-RA suppressed production of dry eye relevant inflammatory mediators [interleukin(IL)-1β, IL-12, regulated upon activation, normal T cell expressed and secreted (RANTES)] by myeloid cells. Systemic VAD was associated with significant goblet cell loss and an increased number of CD45+ immune cells in the conjunctiva. MHCII-CD11b+ classical monocytes were significantly increased in the conjunctiva of VAD C57BL/6 and RXR-α mutated Pinkie strains. RNA seq revealed significantly increased expression of innate immune/inflammatory genes in the Pinkie conjunctiva. These findings indicate that retinoids are essential for maintaining a healthy, well-lubricated ocular surface and have immunomodulatory effects in the conjunctiva that are mediated in part via RXR-α signaling. Perturbation of the homeostatic retinoid axis could potentiate inflammation on the ocular surface.
Keyphrases
- single cell
- oxidative stress
- rna seq
- induced apoptosis
- dendritic cells
- bone marrow
- cell cycle arrest
- innate immune
- acute myeloid leukemia
- rheumatoid arthritis
- immune response
- cell therapy
- poor prognosis
- endoplasmic reticulum stress
- gene expression
- mesenchymal stem cells
- transcription factor
- stem cells
- long non coding rna
- ankylosing spondylitis
- signaling pathway
- optical coherence tomography
- systemic lupus erythematosus
- peripheral blood