June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Chronic Traumatic Encephalopathy is associated with TDP-43 Retinal Pathology
Author Affiliations & Notes
  • Vanessa Goodwill
    Pathology, University of California San Diego, San Diego, California, United States
  • Christina DiLoreto
    Clark County Officer of the Coroner/Medical Examiner, Las Vegas, Nevada, United States
  • Leon Chea
    Pathology, Stanford, Palo Alto, California, United States
  • Christina Sigurdson
    Pathology, University of California San Diego, San Diego, California, United States
  • Victor Alvarez
    Boston University School of Medicine, Boston, Massachusetts, United States
  • Ann McKee
    Boston University School of Medicine, Boston, Massachusetts, United States
  • Jonathan Lin
    Pathology, Stanford, Palo Alto, California, United States
  • Footnotes
    Commercial Relationships   Vanessa Goodwill, None; Christina DiLoreto, None; Leon Chea, None; Christina Sigurdson, None; Victor Alvarez, None; Ann McKee, None; Jonathan Lin, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 5175. doi:
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      Vanessa Goodwill, Christina DiLoreto, Leon Chea, Christina Sigurdson, Victor Alvarez, Ann McKee, Jonathan Lin; Chronic Traumatic Encephalopathy is associated with TDP-43 Retinal Pathology. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5175.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head injury characterized clinically by behavioral problems, mood changes, and memory loss. Although patients with CTE often have associated visual symptoms such as visual blur and diploplia, the ocular pathology, if any, underlying these symptoms is unknown. Brain pathology in CTE is characterized by neuron loss, gliosis, and accumulation of hyperphosphorylated tau, as well as TDP-43 in later stages of the disease. In this study we evaluated the histopathology of eyes collected from 8 patients with autopsy confirmed stage IV CTE, including evaluation for abnormal accumulation of phospho-tau and TDP-43.

Methods : Enucleation specimens from 8 autopsy control patients and 8 patients with CTE were collected. Control patients (ages 62-93) had no known history of traumatic brain injury, and no evidence of CTE on brain autopsy. All CTE patients (ages 61-81) were former athletes in contact sports (football, rugby, or boxing) and had pathologically confirmed stage IV CTE by brain autopsy. Pupil-optic nerve cross sections were prepared and stained with hematoxylin and eosin (H&E), phospho-tau, and phosphorylated TDP-43 (pTDP-43) by immunohistochemistry.

Results : Retinal thickness was comparable between CTE and control eyes by H&E, indicating no overt retinal neurodegeneration in CTE. No phospho-tau pathology was observed in either CTE or normal retinas. pTDP-43 staining was commonly found in CTE eyes (7/8 cases), but rarely seen in control eyes (1/8). The pTDP-43 staining was limited to a discrete subset of inner nuclear layer interneurons of the retina.

Conclusions : Stage IV CTE is associated with a novel retinal neuropathology as identified in this study. Specifically, in the retinas of CTE eyes there is an abnormal cytoplasmic accumulation of pTDP-43 located in a discrete subset of retinal inner nuclear layer interneurons. These interneurons are most consistent with horizontal cells based on morphology and location. These findings may underlie the visual symptoms reported in patients with CTE.

This is a 2020 ARVO Annual Meeting abstract.

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