The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment [version 2; peer review: 2 approved, 1 approved with reservations]
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 associ...
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| Format: | Article |
| Language: | English |
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Wellcome
2022-11-01
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| Series: | Wellcome Open Research |
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| Online Access: | https://wellcomeopenresearch.org/articles/4-130/v2 |
| _version_ | 1797786654074732544 |
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| author | Abebaw Worku Tamsyn Derrick Zerihun Tadesse David C.W. Mabey Bizuayehu Gashaw Matthew J. Burton E. Kelly Callahan Martin J. Holland David Macleod Esmael Habtamu |
| author_facet | Abebaw Worku Tamsyn Derrick Zerihun Tadesse David C.W. Mabey Bizuayehu Gashaw Matthew J. Burton E. Kelly Callahan Martin J. Holland David Macleod Esmael Habtamu |
| author_sort | Abebaw Worku |
| collection | DOAJ |
| description | 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 anti-inflammatory 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. |
| first_indexed | 2024-03-13T01:10:54Z |
| format | Article |
| id | doaj.art-a50df53e912041c9a093165e79744ae5 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-03-13T01:10:54Z |
| publishDate | 2022-11-01 |
| publisher | Wellcome |
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| series | Wellcome Open Research |
| spelling | doaj.art-a50df53e912041c9a093165e79744ae52023-07-06T01:00:00ZengWellcomeWellcome Open Research2398-502X2022-11-01420379The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment [version 2; peer review: 2 approved, 1 approved with reservations]Abebaw Worku0Tamsyn Derrick1Zerihun Tadesse2David C.W. Mabey3Bizuayehu Gashaw4Matthew J. Burton5https://orcid.org/0000-0003-1872-9169E. Kelly Callahan6Martin J. Holland7https://orcid.org/0000-0002-5828-6318David Macleod8https://orcid.org/0000-0002-2371-5709Esmael Habtamu9https://orcid.org/0000-0001-6161-8427Amhara Regional Health Bureau, Bahirdar, EthiopiaLondon School of Hygiene and Tropical Medicine, London, UKThe Carter Center, Addis Ababa, EthiopiaLondon School of Hygiene and Tropical Medicine, London, UKAmhara Regional Health Bureau, Bahirdar, EthiopiaLondon School of Hygiene and Tropical Medicine, London, UKThe Carter Center, Atlanta, USALondon School of Hygiene and Tropical Medicine, London, UKLondon School of Hygiene and Tropical Medicine, London, UKLondon School of Hygiene and Tropical Medicine, London, UKBackground: 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 anti-inflammatory 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.https://wellcomeopenresearch.org/articles/4-130/v2Trichiasis conjunctiva eyelid contour abnormalities post-operative scarring inflammationeng |
| spellingShingle | Abebaw Worku Tamsyn Derrick Zerihun Tadesse David C.W. Mabey Bizuayehu Gashaw Matthew J. Burton E. Kelly Callahan Martin J. Holland David Macleod Esmael Habtamu The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment [version 2; peer review: 2 approved, 1 approved with reservations] Wellcome Open Research Trichiasis conjunctiva eyelid contour abnormalities post-operative scarring inflammation eng |
| title | The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_full | The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_fullStr | The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_full_unstemmed | The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_short | The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment [version 2; peer review: 2 approved, 1 approved with reservations] |
| title_sort | conjunctival transcriptome in ethiopians after trichiasis surgery associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment version 2 peer review 2 approved 1 approved with reservations |
| topic | Trichiasis conjunctiva eyelid contour abnormalities post-operative scarring inflammation eng |
| url | https://wellcomeopenresearch.org/articles/4-130/v2 |
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