A connectomics approach to understanding a retinal disease

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Macular telangiectasia type 2 (MacTel) is a late-onset macular degeneration.
• MacTel is associated with Müller glial cell loss and serine deficiency in the retina.
• The disease is typically confined to a central retinal area known as the MacTel zone.

Observation:

• Electron microscopic connectomics were used to analyze retinal tissue from a MacTel patient.
• Specific mitochondrial structural changes were observed across all retinal cell types, both within and outside the MacTel zone.
• An distinct boundary of the MacTel zone was identified, correlating with Müller cell and macular pigment loss.

Findings:

• Mitochondrial structural abnormalities were a key finding in MacTel retinal tissue.
• The study observed a correlation between the MacTel zone boundary, Müller cell loss, and macular pigment reduction.
• All retinal cell types exhibited mitochondrial changes, suggesting a widespread cellular impact.

Implications:

• Müller cells synthesize serine, an amino acid crucial for mitochondrial maintenance.
• A deficiency in serine may lead to the observed mitochondrial structural changes.
• This serine deficiency is proposed as a potential underlying cause for MacTel development and progression.