Axonal Transport as an In Vivo Biomarker for Retinal Neuropathy

Lucia G. Le Roux, Xudong Qiu, Megan C. Jacobsen, Mark D. Pagel, Seth T. Gammon, David R. Piwnica-Worms, Dawid Schellingerhout

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

We illuminate a possible explanatory pathophysiologic mechanism for retinal cellular neuropathy by means of a novel diagnostic method using ophthalmoscopic imaging and a molecular imaging agent targeted to fast axonal transport. The retinal neuropathies are a group of diseases with damage to retinal neural elements. Retinopathies lead to blindness but are typically diagnosed late, when substantial neuronal loss and vision loss have already occurred. We devised a fluorescent imaging agent based on the non-toxic C fragment of tetanus toxin (TTc), which is taken up and transported in neurons using the highly conserved fast axonal transport mechanism. TTc serves as an imaging biomarker for normal axonal transport and demonstrates impairment of axonal transport early in the course of an N-methyl-D-aspartic acid (NMDA)-induced excitotoxic retinopathy model in rats. Transport-related imaging findings were dramatically different between normal and retinopathic eyes prior to presumed neuronal cell death. This proof-of-concept study provides justification for future clinical translation.

Original languageEnglish (US)
JournalCells
Volume9
Issue number5
DOIs
StatePublished - May 22 2020

Keywords

  • axonal transport
  • clinical translation
  • glaucoma
  • macular degeneration
  • neural biomarker
  • ophthalmoscopy
  • retinal neuropathy

ASJC Scopus subject areas

  • Medicine(all)

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