Ascorbic acid modulation of iron homeostasis and lysosomal function in trabecular meshwork cells

Area of Science:

• Ophthalmology
• Cell Biology
• Biochemistry

Background:

• Trabecular meshwork (TM) cells are crucial for maintaining intraocular pressure.
• Oxidative stress is implicated in the pathogenesis of glaucoma.
• Ascorbic acid (vitamin C) is a potent antioxidant with potential roles in ocular health.

Purpose of the Study:

• To investigate the antioxidant properties of ascorbic acid (AA) on TM cells.
• To elucidate the biological functions of AA in TM cells under oxidative stress.
• To determine the effect of AA on cellular processes like autophagy and lysosomal function.

Main Methods:

• Primary porcine TM cells were cultured and treated with varying concentrations of AA.
• Cell viability was assessed against hydrogen peroxide-induced cytotoxicity.
• Intracellular reactive oxygen species (iROS), redox-active iron, ferritin, and cathepsin levels were quantified.
• Autophagy and lysosomal proteolysis were evaluated using specific assays.

Main Results:

• Ascorbic acid exhibited a concentration-dependent dual effect on TM cells, acting as either an antioxidant or pro-oxidant.
• Pro-oxidant effects were linked to increased intracellular iron, ferritin, and iROS.
• Antioxidant effects correlated with reduced ferritin and basal iROS.
• AA supplementation induced autophagy and enhanced lysosomal proteolysis via cathepsin activation.

Conclusions:

• Decreased ascorbic acid levels in aging individuals may impair lysosomal degradation in TM cells, contributing to glaucoma.
• Restoring physiological vitamin C levels could enhance protein degradation in TM cells and improve tissue function.
• Understanding AA's role is vital for developing therapeutic strategies for glaucoma.