Mitochondrial and microtubule defects in Exfoliation Glaucoma

Area of Science:

• Ophthalmology
• Cell Biology
• Genetics

Background:

• Exfoliation Syndrome (XFS) involves fibrillar material deposition in eye tissues, a risk factor for Exfoliation Glaucoma (XFG).
• XFG shares neurodegenerative disease features, including protein aggregation and oxidative stress.
• XFG patients exhibit mitochondrial dysfunction, evidenced by reduced membrane potential and DNA deletions.

Purpose of the Study:

• To investigate mitochondrial bioenergetics and function in Tenon Capsule Fibroblasts (TFs) from XFG patients.
• To explore the potential therapeutic effects of mitophagy and mitochondrial biogenesis inducers on XFG TFs.

Main Methods:

• Cultured Tenon Capsule Fibroblasts (TFs) from non-glaucoma (NG) and XFG patients.
• Assessed mitochondrial bioenergetics, reactive oxygen species (ROS) levels, mitochondrial morphology, and mitophagy flux.
• Treated XFG TFs with Urolithin A (UA) and Nicotinamide Ribose (NR).

Main Results:

• XFG TFs displayed impaired mitochondrial bioenergetics, increased ROS, smaller mitochondria with dysmorphic cristae, and reduced mitophagy.
• Mitochondrial dysfunction correlated with hyperdynamic microtubules and increased HDAC6 activity.
• UA and NR treatments improved mitochondrial bioenergetics and decreased ROS in XFG TFs.

Conclusions:

• XFG TFs exhibit significant mitochondrial abnormalities and dysfunction.
• Targeting mitophagy pathways with inducers like Urolithin A shows therapeutic potential for XFG.