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

Autor: Jehan Alam, Ebru Yaman, Gerda Cristal Villalba Silva, Rui Chen, Cintia S. de Paiva, Mary Ann Stepp, Stephen C. Pflugfelder
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Medicine, Vol 11 (2024)
Druh dokumentu: article
ISSN: 2296-858X
DOI: 10.3389/fmed.2024.1362336
Popis: BackgroundDry 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.MethodsDesiccating 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.ResultsTwelve 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 p
Databáze: Directory of Open Access Journals