TrkB Activators for the Treatment of Traumatic Vision Loss
Abstract
Pressure waves due to explosions can damage the neurons of the eye and visual centers in the brain, leading to functional loss of vision. There are currently few treatments for such injuries that can be deployed rapidly in the field to mitigate such damage. Our research team is developing small molecule activators of TrkB, the cognate receptor for brain-derived neurotrophic factor (BDNF), which can be administered systemically and cross the blood brain/retina barrier (BBB). In the initial year of this grant, we have developed procedures for damaging the optic nerve and initiated experiments to establish assays for measuring retinal ganglion cell (RGC) loss after optic nerve damage. We developed a novel, rapid assay for ganglion cell death using microplate fluorescence measurements. The time course of retinal ganglion cell loss after optic nerve damage was established, demonstrating that most cell loss occurs during the first six days after trauma. We have developed a new synthesis for HIOC, one of our lead TrkB activators. Drug tests have been initiated, but thus far we have not observed consistent protection from optic nerve crush. We are altering test parameters (dose, timing, administration route) to further assess the utility of the drugs for improving retinal ganglion cell survival after optic nerve crush. We have begun construction of a blast cannon and will begin testing soon.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA606287
Entities
People
- Betty Diamond
- P. M. Iuvone
Organizations
- Emory University