Single cell analysis of short-term dry eye induced changes in cornea immune cell populations.

TitleSingle cell analysis of short-term dry eye induced changes in cornea immune cell populations.
Publication TypeJournal Article
Year of Publication2024
AuthorsAlam, J, Yaman, E, Silva, GCristal Vi, Chen, R, de Paiva, CS, Stepp, MAnn, Pflugfelder, SC
JournalFront Med (Lausanne)
Volume11
Pagination1362336
Date Published2024
ISSN2296-858X
Abstract

BACKGROUND: Dry eye causes corneal inflammation, epitheliopathy and sensorineural changes. This study evaluates the hypothesis that dry eye alters the percentages and transcriptional profiles of immune cell populations in the cornea.

METHODS: Desiccating stress (DS) induced dry eye was created by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Expression profiling of corneal immune cells was performed by single-cell RNA sequencing (scRNA-seq). Cell differentiation trajectories and cell fate were modeled through RNA velocity analysis. Confocal microscopy was used to immunodetect corneal immune cells. Irritation response to topical neurostimulants was assessed.

RESULTS: Twelve corneal immune cell populations based on their transcriptional profiles were identified at baseline and consist of monocytes, resident (rMP) and MMP12/13 high macrophages, dendritic cells (cDC2), neutrophils, mast cells, pre T/B cells, and innate (γDT, ILC2, NK) and conventional T and B lymphocytes. T cells and resident macrophages (rMP) were the largest populations in the normal cornea comprising 18.6 and 18.2 percent, respectively. rMP increased to 55.2% of cells after 5 days of DS. Significant changes in expression of 1,365 genes (adj  

CONCLUSION: These findings indicate that DS recruits monocytes that differentiate to macrophages with increased expression of inflammation associated genes. The proximity of these macrophages to cornea nerves and their expression of neurosensitizers suggests they contribute to the corneal sensorineural changes in dry eye.

DOI10.3389/fmed.2024.1362336
Alternate JournalFront Med (Lausanne)
PubMed ID38560382
PubMed Central IDPMC10978656
Grant ListS10 OD018033 / OD / NIH HHS / United States
U01 EY034692 / EY / NEI NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
S10 OD023469 / OD / NIH HHS / United States
P30 EY002520 / EY / NEI NIH HHS / United States
P30 DK056338 / DK / NIDDK NIH HHS / United States
R01 EY011915 / EY / NEI NIH HHS / United States