June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Lubrication of the ocular surface regenerates the corneal stroma in dry eye disease
Author Affiliations & Notes
  • Yael Efraim
    Cell and Tissue Biology, University of California San Francisco, San Francisco, California, United States
  • Feeling Yu Ting Chen
    Cell and Tissue Biology, University of California San Francisco, San Francisco, California, United States
  • Dylan Pham
    Cell and Tissue Biology, University of California San Francisco, San Francisco, California, United States
  • Sarah Knox
    Cell and Tissue Biology, University of California San Francisco, San Francisco, California, United States
  • Nancy A. McNamara
    Herbert Wertheim School of Optometry and Vision Science, University of California Berkeley, Berkeley, California, United States
    Department of Anatomy, University of California San Francisco, San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Yael Efraim None; Feeling Chen None; Dylan Pham None; Sarah Knox None; Nancy McNamara None
  • Footnotes
    Support  RO1EY025980, RO1EY033040
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4603. doi:
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    • Get Citation

      Yael Efraim, Feeling Yu Ting Chen, Dylan Pham, Sarah Knox, Nancy A. McNamara; Lubrication of the ocular surface regenerates the corneal stroma in dry eye disease. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4603.

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

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Abstract

Purpose : Topical lubrication is the most common method used to relieve the signs and symptoms of dry eye disease. However, the impact of lubrication on ocular structures that are essential to vision, such as the corneal stroma, remains unclear. Here, we investigate the therapeutic potential of topical lubrication on the corneal stroma in the autoimmune regulator knockout (Aire KO) mouse model of autoimmune-mediated dry eye.

Methods : Eyes of 5 Aire KO mice were topically treated with PBS 3xdaily for 14 consecutive days and compared to untreated and wild type (WT) controls. Changes in stromal composition and architecture were analyzed through immunofluorescent detection of keratocytes, immune cells, and extracellular matrix components. Alterations in stromal cell identities were determined via single nuclei (sn)RNA-seq (5 mice/group) using a 10x genomics pipeline. Stromal cell subpopulations, lineage trajectories and signaling pathways involved with disease and treatment were identified using Seurat, Slingshot and Cellchat, respectively. snRNAseq outcomes were then validated through a combination of in situ hybridization/immunofluorescence and 3D imaging.

Results : snRNAseq identified 6 keratocyte populations in the WT stroma that were significantly changed in the Aire KO. Specifically, a potential progenitor cluster marked by Cd34/Txnb was depleted whereas Col6a1+/Col1a1+ cells were expanded. In addition, immunofluorescent analysis highlighted an accompanying elevation in MAPK activation, indicative of a pathogenic state. Despite persistent inflammation, PBS significantly restored the expression of basement membrane components such as laminin and perlecan, and rescued collagen fiber alignment essential for vision. Although PBS did not promote the expansion of Cd34+/Txnb+ cells in Aire KO mice, it did reduce the expansion of Col6a1+/Col1a1+ cells and the activation of MAPK. PBS also promoted the expansion of a potentially reparative cell cluster, marked by Ptn/Nampt/Igf1, and enrichment in IGF-signaling.

Conclusions : We show that topical lubrication promotes regeneration of the stromal compartment, potentially shifting keratocytes into a reparative state for regenerating the stroma through an IGF signaling pathway.

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

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