TDP43 pathology in chronic traumatic encephalopathy retinas

Area of Science:

• Neuroscience
• Ophthalmology
• Neuropathology

Background:

• Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease linked to repetitive head trauma.
• Brain pathology in CTE involves neuronal loss, gliosis, and abnormal tau (p-tau) and TDP43 (p-TDP43) protein accumulation.
• Patients with CTE report visual anomalies, but the underlying ocular pathology remains unclear.

Purpose of the Study:

• To investigate retinal pathology in individuals with confirmed stage IV CTE.
• To compare ocular findings in CTE patients with a control group without CTE or head injury history.
• To identify potential links between retinal changes and visual deficits in CTE.

Main Methods:

• Post-mortem retinal tissues from 8 CTE athletes and 8 controls were analyzed.
• Tissues were stained using hematoxylin and eosin (H&E) and immunohistochemistry for p-tau, p-TDP43, and total TDP43.
• Pupil-optic nerve cross sections were examined for cellular changes and protein deposition.

Main Results:

• No significant general retinal degeneration was observed between CTE and control groups via H&E staining.
• Strong cytoplasmic p-TDP43 and total TDP43 staining was identified in inner nuclear layer interneurons (likely horizontal cells) in 6/8 CTE retinas.
• Only 1/8 control retinas showed similar p-TDP43 pathology; no p-tau pathology was found in either group.

Conclusions:

• Novel retinal phospho-TDP43 pathology, specifically in inner nuclear layer interneurons, is identified in CTE.
• These findings suggest a potential role for retinal p-TDP43 accumulation in the visual disturbances experienced by CTE patients.
• Further research is warranted to elucidate the precise mechanisms linking retinal TDP43 pathology to visual deficits in CTE.