Dexamethasone Impairs ATP Production and Mitochondrial Performance in Human Trabecular Meshwork Cells

Area of Science:

• Ophthalmology
• Cell Biology
• Metabolic Research

Background:

• Mitochondrial damage is implicated in normal aging and open-angle glaucoma.
• Human trabecular meshwork (HTM) cells are crucial for maintaining ocular pressure.
• Glaucoma research often utilizes in vitro models with dexamethasone (Dex) and TGF-β2.

Purpose of the Study:

• To quantify mitochondrial function and ATP generation in HTM cells treated with Dex and TGF-β2.
• To investigate the impact of Dex and TGF-β2 on mitochondrial biogenesis and oxidative stress markers.
• To assess the utility of HTM cell models for studying glaucoma-related mitochondrial dysfunction.

Main Methods:

• Primary HTM cells were cultured and treated with Dex or TGF-β2.
• Seahorse XFp Analyzer was used to measure cellular metabolic function, including respiration and ATP production.
• Mitochondrial copy number and key gene expression (biogenesis, oxidative stress) were analyzed.

Main Results:

• Dex treatment significantly decreased total ATP production and ATP derived from oxidative phosphorylation.
• Maximal respiration, ATP-linked oxygen consumption, and non-mitochondrial oxygen consumption were reduced by Dex.
• TGF-β2 treatment did not significantly alter mitochondrial function.
• No significant changes were observed in mitochondrial genome levels or related mRNA transcripts.

Conclusions:

• Dexamethasone significantly impairs mitochondrial performance and ATP generation in HTM cells, supporting its use in in vitro glaucoma models.
• These findings align with existing research on Dex effects and in vivo evidence of mitochondrial damage in glaucoma.
• Further investigation into Dex-induced mitochondrial dysfunction in glaucoma is warranted.