The dual role of dexamethasone on anti-inflammation and outflow resistance demonstrated in cultured human trabecular meshwork cells.
OBJECTIVE
Dexamethasone (DEX) is a glucocorticoid commonly used in topical eyedrops to treat eye inflammation. It has an undesirable effect of inducing glaucoma in certain patients. In human Trabecular Meshwork (TM) cells DEX regulates a number of genes but its global influence on TM gene expression is still elusive. In the present work, DEX effects on global gene expressions of an established human TM cell line were studied by microarray.


METHODS
The whole experiment of microarray was repeated three times. Differentially expressed genes were identified by an empirical Bayes approach and confirmed by Reverse Transcription Polymerase Chain Reaction.


RESULTS
Eight genes (GAS1, CDH4, MT1L, CST3, ATF4, ASNS/TS11, CHOP, HSPA5) were identified that are at least a thousand times more likely to be differentially expressed due to DEX treatment and six genes (TSC22, LDHA, IGFBP2, TAGLN, SCG2, WARS) were identified that are at least a hundred times more likely to be differentially expressed due to DEX treatment. Except for MT1L, ASNS/TS11, IGFBP2, SCG2, and WARS, all the other genes are first reported here to be regulated by DEX in TM. Intriguingly, several of them have overlapping roles in anti-inflammatory response and outflow resistance.


CONCLUSIONS
The results of our experiments on cultured human TM cells indicate that the increase in outflow resistance and ultimate ocular hypertension may be byproducts of the favorable anti-inflammatory response triggered by DEX.
Leung
Yuk Fai
YF
Department of Ophthalmology Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
Tam
Pancy Oi Sin
PO
Lee
Wing Shan
WS
Lam
Dennis Shun Chiu
DS
Yam
Hin Fai
HF
Fan
Bao Jian
BJ
Tham
Clement Chee Yung
CC
Chua
John Kien Han
JK
Pang
Chi Pui
CP
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001082:Aqueous Humor / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D005136:Eye Proteins; D005938:Glucocorticoids; C000717247:HSPA5 protein, human; D003907:Dexamethasone