Sustained stress response after oxidative stress in trabecular meshwork cells

Area of Science:

• Ocular biology
• Cellular stress response
• Glaucoma pathogenesis

Background:

• Glaucoma is associated with sustained stress responses in the trabecular meshwork (TM).
• Chronic oxidative stress is implicated as a potential trigger for these responses.

Purpose of the Study:

• To investigate how chronic oxidative stress induces a sustained stress response in TM cells.
• To identify the mechanisms linking oxidative stress to inflammatory markers in TM.

Main Methods:

• Porcine TM cells were exposed to hydrogen peroxide (H2O2) to simulate chronic oxidative stress.
• Analyzed intracellular reactive oxygen species (iROS) generation, mitochondrial potential, NF-kappaB activation, and inflammatory marker expression (IL-1alpha, IL-6, IL-8, ELAM-1).
• Utilized specific inhibitors to identify the sources of iROS and the role of NF-kappaB.

Main Results:

• H2O2-induced chronic oxidative stress led to sustained mitochondrial iROS production in TM cells.
• Inhibition of mitochondrial iROS significantly reduced NF-kappaB activation and inflammatory marker induction.
• NF-kappaB inhibition partially reduced the induction of IL-1alpha, IL-8, and ELAM-1, but not IL-6.

Conclusions:

• Chronic oxidative stress in TM cells stimulates mitochondrial iROS production.
• Mitochondrial iROS and subsequent NF-kappaB activation contribute to the expression of inflammatory mediators in TM.
• These findings suggest a mechanism by which oxidative stress may drive glaucoma pathogenesis through inflammation and tissue damage.