Human Conjunctival Transcriptome in Acanthamoeba Keratitis: An Exploratory Study.

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TitleHuman Conjunctival Transcriptome in Acanthamoeba Keratitis: An Exploratory Study.
Publication TypeJournal Article
Year of Publication2024
AuthorsSeitzman GD, Keenan JD, Lietman TM, Ruder K, Zhong L, Chen C, Liu YH, Yu D, Abraham T, Hinterwirth A, Doan T
Corporate AuthorscapriCORN(Comprehensive Analysis of Pathogens, Resistomes, and Inflammatory markers in the CORNea) Study Group
Date Published2024 May 21

PURPOSE: The purpose of this study was to identify conjunctival transcriptome differences in patients with Acanthamoeba keratitis compared with keratitis with no known associated pathogen.

METHODS: The host conjunctival transcriptome of 9 patients with Acanthamoeba keratitis (AK) is compared with the host conjunctival transcriptome of 13 patients with pathogen-free keratitis. Culture and/or confocal confirmed Acanthamoeba in 8 of 9 participants with AK who underwent metagenomic RNA sequencing as the likely pathogen. Cultures were negative in all 13 cases where metagenomic RNA sequencing did not identify a pathogen.

RESULTS: Transcriptome analysis identified 36 genes differently expressed between patients with AK and patients with presumed sterile, or pathogen-free, keratitis. Gene enrichment analysis revealed that some of these genes participate in several biologic pathways important for cellular signaling, ion transport and homeostasis, glucose transport, and mitochondrial metabolism. Notable relatively differentially expressed genes with potential relevance to Acanthamoeba infection included CPS1, SLC35B4, STEAP2, ATP2B2, NMNAT3, and AKAP12.

CONCLUSIONS: This research suggests that the local transcriptome in Acanthamoeba keratitis may be sufficiently robust to be detected in the conjunctiva and that corneas infected with Acanthamoeba may be distinguished from the inflamed cornea where no pathogen was identified. Given the low sensitivity for corneal cultures, identification of differentially expressed genes may serve as a suggestive transcriptional signature allowing for a complementary diagnostic technique to identify this blinding parasite. Knowledge of differentially expressed genes may also direct investigation of disease pathophysiology and suggest novel pathways for therapeutic targets.

Alternate JournalCornea
PubMed ID38771726
Grant ListR01EY032861 / EY / NEI NIH HHS / United States
K12EY031372 / EY / NEI NIH HHS / United States