The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.

The pathophysiology of dry eye disease (DED) remains largely unknown, accounting in part for the lack of successful treatments. We explored the pathophysiology of DED using a rabbit model of chronic DED induced with 3 weekly injections of Concanavalin A into the periorbital lacrimal glands. The tran...

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Autores principales: Adam Master, Apostolos Kontzias, Liqun Huang, Wei Huang, Anna Tsioulias, Samaneh Zarabi, Michael Wolek, Brian M Wollocko, Robert Honkanen, Basil Rigas
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:36dcf440107e4984b9e4971a2c8313612021-12-02T20:08:59ZThe transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.1932-620310.1371/journal.pone.0254036https://doaj.org/article/36dcf440107e4984b9e4971a2c8313612021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254036https://doaj.org/toc/1932-6203The pathophysiology of dry eye disease (DED) remains largely unknown, accounting in part for the lack of successful treatments. We explored the pathophysiology of DED using a rabbit model of chronic DED induced with 3 weekly injections of Concanavalin A into the periorbital lacrimal glands. The transcriptome of full-thickness's conjunctival tissue from rabbits with DED and from normal controls was determined using microarrays and, as needed, confirmatory real-time polymerase chain reactions. Results were subjected to bioinformatic analysis. DED induced large-scale changes in gene transcription involving 5,184 genes (22% of the total). Differentially expressed genes could be segregated into: functional modules and clusters; altered pathways; functionally linked genes; and groups of individual genes of known or suspected pathophysiological relevance to DED. A common feature of these subgroups is the breadth and magnitude of the changes that encompass ocular immunology and essentially all aspects of cell biology. Prominent changes concerned innate and adaptive immune responses; ocular surface inflammation; at least 25 significantly altered signaling pathways; a large number of chemokines; cell cycle; and apoptosis. Comparison of our findings to the limited extant transcriptomic data from DED patients associated with either Sjogren's syndrome or non-Sjogren's etiologies revealed a significant correlation between human and rabbit DED transcriptomes. Our data, establishing the large-scale transcriptomic changes of DED and their potential similarity to the human, underscore the enormous complexity of DED; establish a robust animal model of DED; will help expand our understanding of its pathophysiology; and could guide the development of successful therapeutic strategies.Adam MasterApostolos KontziasLiqun HuangWei HuangAnna TsiouliasSamaneh ZarabiMichael WolekBrian M WollockoRobert HonkanenBasil RigasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254036 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Adam Master
Apostolos Kontzias
Liqun Huang
Wei Huang
Anna Tsioulias
Samaneh Zarabi
Michael Wolek
Brian M Wollocko
Robert Honkanen
Basil Rigas
The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.
description The pathophysiology of dry eye disease (DED) remains largely unknown, accounting in part for the lack of successful treatments. We explored the pathophysiology of DED using a rabbit model of chronic DED induced with 3 weekly injections of Concanavalin A into the periorbital lacrimal glands. The transcriptome of full-thickness's conjunctival tissue from rabbits with DED and from normal controls was determined using microarrays and, as needed, confirmatory real-time polymerase chain reactions. Results were subjected to bioinformatic analysis. DED induced large-scale changes in gene transcription involving 5,184 genes (22% of the total). Differentially expressed genes could be segregated into: functional modules and clusters; altered pathways; functionally linked genes; and groups of individual genes of known or suspected pathophysiological relevance to DED. A common feature of these subgroups is the breadth and magnitude of the changes that encompass ocular immunology and essentially all aspects of cell biology. Prominent changes concerned innate and adaptive immune responses; ocular surface inflammation; at least 25 significantly altered signaling pathways; a large number of chemokines; cell cycle; and apoptosis. Comparison of our findings to the limited extant transcriptomic data from DED patients associated with either Sjogren's syndrome or non-Sjogren's etiologies revealed a significant correlation between human and rabbit DED transcriptomes. Our data, establishing the large-scale transcriptomic changes of DED and their potential similarity to the human, underscore the enormous complexity of DED; establish a robust animal model of DED; will help expand our understanding of its pathophysiology; and could guide the development of successful therapeutic strategies.
format article
author Adam Master
Apostolos Kontzias
Liqun Huang
Wei Huang
Anna Tsioulias
Samaneh Zarabi
Michael Wolek
Brian M Wollocko
Robert Honkanen
Basil Rigas
author_facet Adam Master
Apostolos Kontzias
Liqun Huang
Wei Huang
Anna Tsioulias
Samaneh Zarabi
Michael Wolek
Brian M Wollocko
Robert Honkanen
Basil Rigas
author_sort Adam Master
title The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.
title_short The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.
title_full The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.
title_fullStr The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.
title_full_unstemmed The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.
title_sort transcriptome of rabbit conjunctiva in dry eye disease: large-scale changes and similarity to the human dry eye.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/36dcf440107e4984b9e4971a2c831361
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