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Title: Dexamethasone Impairs ATP Production and Mitochondrial Performance in Human Trabecular Meshwork Cells
Mitochondrial damage occurs in human trabecular meshwork (HTM) cells as a result of normal aging and in open angle glaucoma. Using an HTM cell model, we quantified mitochondrial function and ATP generation rates after dexamethasone (Dex) and TGF-β2 treatments, frequently used as in vitro models of glaucoma. Primary HTM cells were assayed for metabolic function using a Seahorse XFp Analyzer. We additionally assessed the mitochondrial copy number and the expression of transcripts associated with mitochondrial biogenesis and oxidative stress regulation. Cells treated with Dex, but not TGF-β2, exhibited a significant decrease in total ATP production and ATP from oxidative phosphorylation relative to that of the control. Dex treatment also resulted in significant decreases in maximal respiration, ATP-linked O2 consumption, and non-mitochondrial O2 consumption. We did not observe significant changes in the level of mitochondrial genomes or mRNA transcripts of genes involved in mitochondrial biogenesis and oxidative stress regulation. Decreased mitochondrial performance and ATP production are consistent with the results of prior studies identifying the effects of Dex on multiple cell types, including HTM cells. Our results are also consistent with in vivo evidence of mitochondrial damage in open-angle glaucoma. Overall, these results demonstrate a decrease in mitochondrial performance in Dex-induced glaucomatous models in vitro, meriting further investigation.  more » « less
Award ID(s):
2046093
PAR ID:
10575921
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
Multidisciplinary Digital Publishing Institute
Date Published:
Journal Name:
Current Issues in Molecular Biology
Volume:
46
Issue:
9
ISSN:
1467-3045
Page Range / eLocation ID:
9867 to 9880
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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