Cortical gradient compression links cognition and transcriptomic signatures in primary angle-closure glaucoma.

Area of Science:

• Neuroscience
• Ophthalmology
• Genetics

Background:

• The cerebral cortex has hierarchical functional gradients integrating sensory and cognitive processes.
• It remains unclear if primary angle-closure glaucoma (PACG) disrupts these gradients and causes cognitive impairment.

Purpose of the Study:

• To investigate cortical functional gradient alterations in PACG patients.
• To explore the association between these alterations and cognitive decline.

Main Methods:

• Resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyze brain activity.
• Transcriptomic analyses identified associated molecular pathways.

Main Results:

• PACG patients showed compressed and reorganized cortical gradients, especially in visual and default mode networks.
• These cortical changes correlated with poorer visual performance and cognitive decline.
• Genes linked to gradient disruption were enriched in synaptic signaling, neurodevelopment, and astrocyte pathways.

Conclusions:

• Primary angle-closure glaucoma leads to cortical hierarchical remodeling.
• This remodeling and its molecular underpinnings offer insights into the neural basis of cognitive impairment in PACG.