Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro

Kandasamy Kathirvel; Lester Karen; Ravinarayanan Haribalaganesh; Ramasamy Krishnadas; Veerappan Muthukkaruppan; Brian Lane; David A. Simpson; Kasia Goljanek-whysall; Carl Sheridan; Devarajan Bharanidharan; Colin E. Willoughby; Srinivasan Senthilkumari

doi:10.1038/s41598-022-12443-7

Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro

Kandasamy Kathirvel, Lester Karen, Ravinarayanan Haribalaganesh, Ramasamy Krishnadas, Veerappan Muthukkaruppan, Brian Lane, David A. Simpson, Kasia Goljanek-whysall, Carl Sheridan, Devarajan Bharanidharan, Colin E. Willoughby, Srinivasan Senthilkumari

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Abstract

In the quest of identifying newer molecular targets for the management of glucocorticoid-induced ocular hypertension (GC-OHT) and glaucoma (GCG), several microarray studies have attempted to investigate the genome-wide transcriptome profiling of primary human trabecular meshwork (TM) cells in response to dexamethasone (DEX). However, no studies are reported so far to demonstrate the temporal changes in the expression of genes in the cultured human TM cells in response to DEX treatment. Therefore, in the present study, the time-dependent changes in the genome-wide expression of genes in primary human TM cells after short (16 hours: 16 h) and long exposure (7 days: 7 d) of DEX was investigated using RNA sequencing. There were 199 (118 up-regulated; 81 down-regulated) and 525 (119 up-regulated; 406 down-regulated) DEGs in 16 h and 7 d treatment groups respectively. The unique genes identified in 16 h and 7 d treatment groups were 152 and 478 respectively. This study found a distinct gene signature and pathways between two treatment regimes. Longer exposure of DEX treatment showed a dys-regulation of Wnt and Rap1 signaling and so highlighted potential therapeutic targets for pharmacological management of GC-OHT/glaucoma.

Original language	English
Article number	8299
Pages (from-to)	1-11
Number of pages	11
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-12443-7
Publication status	Published (in print/issue) - 1 Dec 2022

Bibliographical note

Funding Information:
This study was supported by the Department of Biotechnology (DBT)-Wellcome Trust/India Alliance fellowship ([Grant Number: IA/I/16/2/502694] awarded to Dr. Senthilkumari Srinivasan) and Glaucoma UK; Fight for Sight (UK) [Grant awarded to Professor Colin E Willoughby]; NC3Rs PhD studentship (UK) [Grant awarded to Dr Carl Sheridan and Professor Colin E Willoughby].

Funding Information:
The authors acknowledge the Rotary Aravind International Eye Bank, Aravind Eye Hospital, Madurai, India and the Liverpool Research Eye Bank, University of Liverpool, United Kingdom for providing human donor eyes for 16 h and 7 d treatment groups respectively for the present study.

Publisher Copyright:
© 2022, The Author(s).

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Kathirvel, K., Karen, L., Haribalaganesh, R., Krishnadas, R., Muthukkaruppan, V., Lane, B., Simpson, D. A., Goljanek-whysall, K., Sheridan, C., Bharanidharan, D., Willoughby, C. E., & Senthilkumari, S. (2022). Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro. Scientific Reports, 12(1), 1-11. Article 8299. https://doi.org/10.1038/s41598-022-12443-7

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abstract = "In the quest of identifying newer molecular targets for the management of glucocorticoid-induced ocular hypertension (GC-OHT) and glaucoma (GCG), several microarray studies have attempted to investigate the genome-wide transcriptome profiling of primary human trabecular meshwork (TM) cells in response to dexamethasone (DEX). However, no studies are reported so far to demonstrate the temporal changes in the expression of genes in the cultured human TM cells in response to DEX treatment. Therefore, in the present study, the time-dependent changes in the genome-wide expression of genes in primary human TM cells after short (16 hours: 16 h) and long exposure (7 days: 7 d) of DEX was investigated using RNA sequencing. There were 199 (118 up-regulated; 81 down-regulated) and 525 (119 up-regulated; 406 down-regulated) DEGs in 16 h and 7 d treatment groups respectively. The unique genes identified in 16 h and 7 d treatment groups were 152 and 478 respectively. This study found a distinct gene signature and pathways between two treatment regimes. Longer exposure of DEX treatment showed a dys-regulation of Wnt and Rap1 signaling and so highlighted potential therapeutic targets for pharmacological management of GC-OHT/glaucoma.",

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note = "Funding Information: This study was supported by the Department of Biotechnology (DBT)-Wellcome Trust/India Alliance fellowship ([Grant Number: IA/I/16/2/502694] awarded to Dr. Senthilkumari Srinivasan) and Glaucoma UK; Fight for Sight (UK) [Grant awarded to Professor Colin E Willoughby]; NC3Rs PhD studentship (UK) [Grant awarded to Dr Carl Sheridan and Professor Colin E Willoughby]. Funding Information: The authors acknowledge the Rotary Aravind International Eye Bank, Aravind Eye Hospital, Madurai, India and the Liverpool Research Eye Bank, University of Liverpool, United Kingdom for providing human donor eyes for 16 h and 7 d treatment groups respectively for the present study. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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Kathirvel, K, Karen, L, Haribalaganesh, R, Krishnadas, R, Muthukkaruppan, V, Lane, B, Simpson, DA, Goljanek-whysall, K, Sheridan, C, Bharanidharan, D, Willoughby, CE & Senthilkumari, S 2022, 'Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro', Scientific Reports, vol. 12, no. 1, 8299, pp. 1-11. https://doi.org/10.1038/s41598-022-12443-7

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T1 - Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro

AU - Kathirvel, Kandasamy

AU - Karen, Lester

AU - Haribalaganesh, Ravinarayanan

AU - Krishnadas, Ramasamy

AU - Muthukkaruppan, Veerappan

AU - Lane, Brian

AU - Simpson, David A.

AU - Goljanek-whysall, Kasia

AU - Sheridan, Carl

AU - Bharanidharan, Devarajan

AU - Willoughby, Colin E.

AU - Senthilkumari, Srinivasan

N1 - Funding Information: This study was supported by the Department of Biotechnology (DBT)-Wellcome Trust/India Alliance fellowship ([Grant Number: IA/I/16/2/502694] awarded to Dr. Senthilkumari Srinivasan) and Glaucoma UK; Fight for Sight (UK) [Grant awarded to Professor Colin E Willoughby]; NC3Rs PhD studentship (UK) [Grant awarded to Dr Carl Sheridan and Professor Colin E Willoughby]. Funding Information: The authors acknowledge the Rotary Aravind International Eye Bank, Aravind Eye Hospital, Madurai, India and the Liverpool Research Eye Bank, University of Liverpool, United Kingdom for providing human donor eyes for 16 h and 7 d treatment groups respectively for the present study. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - In the quest of identifying newer molecular targets for the management of glucocorticoid-induced ocular hypertension (GC-OHT) and glaucoma (GCG), several microarray studies have attempted to investigate the genome-wide transcriptome profiling of primary human trabecular meshwork (TM) cells in response to dexamethasone (DEX). However, no studies are reported so far to demonstrate the temporal changes in the expression of genes in the cultured human TM cells in response to DEX treatment. Therefore, in the present study, the time-dependent changes in the genome-wide expression of genes in primary human TM cells after short (16 hours: 16 h) and long exposure (7 days: 7 d) of DEX was investigated using RNA sequencing. There were 199 (118 up-regulated; 81 down-regulated) and 525 (119 up-regulated; 406 down-regulated) DEGs in 16 h and 7 d treatment groups respectively. The unique genes identified in 16 h and 7 d treatment groups were 152 and 478 respectively. This study found a distinct gene signature and pathways between two treatment regimes. Longer exposure of DEX treatment showed a dys-regulation of Wnt and Rap1 signaling and so highlighted potential therapeutic targets for pharmacological management of GC-OHT/glaucoma.

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Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro

Abstract

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