Macular telangiectasia type 2: An update

Area of Science:

• Ophthalmology
• Genetics
• Metabolomics

Background:

• Macular telangiectasia type 2 (MacTel 2) is a complex genetic disorder with unknown causes in most patients.
• Dysregulated serine and lipid metabolism, leading to cytotoxic 1-deoxysphingolipid accumulation, is implicated in MacTel 2 pathogenesis.
• The retinal pigment epithelium's role and the timing of vascular changes in MacTel 2 are increasingly recognized.

Purpose of the Study:

• To review the current understanding of MacTel 2 pathogenesis, focusing on genetic, metabolic, and vascular aspects.
• To discuss the evolving view of MacTel 2 as a disorder with parallel neurodegenerative and vascular changes.
• To highlight potential therapeutic strategies targeting metabolic dysfunction and mitochondrial impairment.

Main Methods:

• Review of genetic and metabolomic studies.
• Analysis of optical coherence tomography angiography findings.
• Correlation of structural (ellipsoid zone loss) and functional (microperimetry) measures.

Main Results:

• Serine deficiency causes 1-deoxysphingolipid accumulation, damaging retinal cells.
• Vascular changes in MacTel 2 may occur earlier and in parallel with neurodegeneration.
• A strong correlation exists between ellipsoid zone loss and retinal sensitivity.

Conclusions:

• MacTel 2 pathogenesis involves complex genetic and metabolic factors, with significant retinal pigment epithelium involvement.
• Therapeutic strategies targeting serine supplementation, 1-deoxysphingolipid reduction, and mitochondrial function are promising.
• Ellipsoid zone loss is a validated surrogate endpoint for clinical trials in MacTel 2.