The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment.
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| Title: | The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment. |
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| Authors: | Derrick, Tamsyn1,2, Habtamu, Esmael1,3, Tadesse, Zerihun3, Callahan, E. Kelly4, Worku, Abebaw5, Gashaw, Bizuayehu5, Macleod, David1, Mabey, David C. W.1, Holland, Martin J.1, Burton, Matthew J.1 matthew.burton@lshtm.ac.uk |
| Source: | Wellcome Open Research. 2022, Vol. 7, p1-26. 26p. |
| Subject Terms: | Transcriptomes, Ethiopians, Eye diseases, Doxycycline, Drug efficacy |
| Abstract: | Background: Surgery to correct trichiasis is a key component of the World Health Organisation trachoma control strategy, however unfavourable outcomes such as eyelid contour abnormalities (ECA) following surgery are relatively common. This study aimed to understand the transcriptional changes associated with the early development of ECA and the impact of doxycycline, which has antiinflammatory and anti-fibrotic properties, upon these transcription patterns. Methods: One thousand Ethiopians undergoing trichiasis surgery were enrolled in a randomised controlled trial following informed consent. Equal groups of randomly assigned individuals were orally administered with 100mg/day of doxycycline (n=499) or placebo (n=501) for 28 days. Conjunctival swabs were collected immediately prior to surgery and at one- and six-months post-surgery. 3’ mRNA sequencing was performed on paired baseline and one-month samples from 48 individuals; 12 in each treatment/outcome group (Placebo-Good outcome, Placebo-Poor outcome, Doxycycline-Good outcome, Doxycycline-Poor outcome). qPCR validation was then performed for 46 genes of interest in 145 individuals who developed ECA at one month and 145 matched controls, using samples from baseline, one and six months. Results: All treatment/outcome groups upregulated genes associated with wound healing pathways at one month relative to baseline, however no individual differences were detected between groups. The summed expression of a highly coexpressed cluster of pro-fibrotic genes was higher in patients that developed ECA in the placebo group relative to controls. qPCR validation revealed that all genes in this cluster and a number of other pro-inflammatory genes were strongly associated with ECA, however these associations were not modulated by trial arm. Conclusions: The development of post-operative ECA is associated with overexpression of pro-inflammatory and pro-fibrotic genes including growth factors, matrix metalloproteinases, collagens and extracellular matrix proteins. There was no evidence that doxycycline modulated the association between gene expression and ECA. [ABSTRACT FROM AUTHOR] |
| Copyright of Wellcome Open Research is the property of Wellcome Trust and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | GreenFILE |
| FullText | Text: Availability: 0 |
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| Header | DbId: 8gh DbLabel: GreenFILE An: 174043153 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Derrick%2C+Tamsyn%22">Derrick, Tamsyn</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Habtamu%2C+Esmael%22">Habtamu, Esmael</searchLink><relatesTo>1,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Tadesse%2C+Zerihun%22">Tadesse, Zerihun</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Callahan%2C+E%2E+Kelly%22">Callahan, E. Kelly</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Worku%2C+Abebaw%22">Worku, Abebaw</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Gashaw%2C+Bizuayehu%22">Gashaw, Bizuayehu</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Macleod%2C+David%22">Macleod, David</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Mabey%2C+David+C%2E+W%2E%22">Mabey, David C. W.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Holland%2C+Martin+J%2E%22">Holland, Martin J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Burton%2C+Matthew+J%2E%22">Burton, Matthew J.</searchLink><relatesTo>1</relatesTo><i> matthew.burton@lshtm.ac.uk</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Wellcome+Open+Research%22">Wellcome Open Research</searchLink>. 2022, Vol. 7, p1-26. 26p. – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Transcriptomes%22">Transcriptomes</searchLink><br /><searchLink fieldCode="DE" term="%22Ethiopians%22">Ethiopians</searchLink><br /><searchLink fieldCode="DE" term="%22Eye+diseases%22">Eye diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Doxycycline%22">Doxycycline</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+efficacy%22">Drug efficacy</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background: Surgery to correct trichiasis is a key component of the World Health Organisation trachoma control strategy, however unfavourable outcomes such as eyelid contour abnormalities (ECA) following surgery are relatively common. This study aimed to understand the transcriptional changes associated with the early development of ECA and the impact of doxycycline, which has antiinflammatory and anti-fibrotic properties, upon these transcription patterns. Methods: One thousand Ethiopians undergoing trichiasis surgery were enrolled in a randomised controlled trial following informed consent. Equal groups of randomly assigned individuals were orally administered with 100mg/day of doxycycline (n=499) or placebo (n=501) for 28 days. Conjunctival swabs were collected immediately prior to surgery and at one- and six-months post-surgery. 3’ mRNA sequencing was performed on paired baseline and one-month samples from 48 individuals; 12 in each treatment/outcome group (Placebo-Good outcome, Placebo-Poor outcome, Doxycycline-Good outcome, Doxycycline-Poor outcome). qPCR validation was then performed for 46 genes of interest in 145 individuals who developed ECA at one month and 145 matched controls, using samples from baseline, one and six months. Results: All treatment/outcome groups upregulated genes associated with wound healing pathways at one month relative to baseline, however no individual differences were detected between groups. The summed expression of a highly coexpressed cluster of pro-fibrotic genes was higher in patients that developed ECA in the placebo group relative to controls. qPCR validation revealed that all genes in this cluster and a number of other pro-inflammatory genes were strongly associated with ECA, however these associations were not modulated by trial arm. Conclusions: The development of post-operative ECA is associated with overexpression of pro-inflammatory and pro-fibrotic genes including growth factors, matrix metalloproteinases, collagens and extracellular matrix proteins. There was no evidence that doxycycline modulated the association between gene expression and ECA. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Wellcome Open Research is the property of Wellcome Trust and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.12688/wellcomeopenres.15419.1 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 26 StartPage: 1 Subjects: – SubjectFull: Transcriptomes Type: general – SubjectFull: Ethiopians Type: general – SubjectFull: Eye diseases Type: general – SubjectFull: Doxycycline Type: general – SubjectFull: Drug efficacy Type: general Titles: – TitleFull: The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Derrick, Tamsyn – PersonEntity: Name: NameFull: Habtamu, Esmael – PersonEntity: Name: NameFull: Tadesse, Zerihun – PersonEntity: Name: NameFull: Callahan, E. Kelly – PersonEntity: Name: NameFull: Worku, Abebaw – PersonEntity: Name: NameFull: Gashaw, Bizuayehu – PersonEntity: Name: NameFull: Macleod, David – PersonEntity: Name: NameFull: Mabey, David C. W. – PersonEntity: Name: NameFull: Holland, Martin J. – PersonEntity: Name: NameFull: Burton, Matthew J. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 01 Text: 2022 Type: published Y: 2022 Identifiers: – Type: issn-print Value: 2398502X Numbering: – Type: volume Value: 7 Titles: – TitleFull: Wellcome Open Research Type: main |
| ResultId | 1 |
