Axonal Transport as an In Vivo Biomarker for Retinal Neuropathy.

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

doi:10.3390/cells9051298

Lucia G Le Roux, Xudong Qiu + Show 5 more

Open Access

https://doi.org/10.3390/cells9051298

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Journal: Cells	Publication Date: May 22, 2020
Citations: 4	License type: CC BY 4.0

Affiliation: The University of Texas MD Anderson Cancer Center

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.

Highlights

The leading causes of vision loss for individuals 40 years and older across all ethnicities are retinopathies
Imaging was done with a confocal scanning laser ophthalmoscope (CSLO), designed for clinical retinal ophthalmic imaging (Figure 2A)
The TTc-488 signal localized to the retinal ganglion cells (RGCs) presenting as individual foci of fluorescence and to the retinal axons (RAs), which were visible in a linear radial pattern

Summary

Introduction

The leading causes of vision loss for individuals 40 years and older across all ethnicities are retinopathies. The retinopathies are a family of diseases that share the common hallmark feature of loss of the neural elements of the retina, for which there are currently no restorative treatments [4]. The retinal ganglion cells (RGCs) and their associated retinal axons (RAs) are well known neuronal targets of retinopathies in general, these cells being the final common pathway for information to leave the retina and travel to the brain proper through the optic nerve, which is comprised of RGC axons. In particular, is known to have RGC damage as its principal feature, and the measurement of this damage has been the focus of much research. RGC damage is currently measured clinically by using visual field testing or automated perimetry, or by measuring retinal nerve fiber layer (RNFL)

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