Abstract
Purpose :
Current treatments for traumatic optic neuropathy (TON) are largely ineffective and have adverse side effects. Development of more effective treatments is hindered by a lack of understanding of the molecular mechanisms underlying TON, as well as the lack of a relevant animal model. To address these limitations, we have developed a realistic rat model [Asemota et al., ARVO 2014], in which we are investigating the pathophysiological and molecular responses to torsional indirect TON (TITON). Earlier work from our group, using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS), suggested that the pattern of protein expression was modified in the optic nerve of TITON rats, compared to controls [Glickman et al., ARVO 2014]. In the current work, we tested the hypothesis that the induction of torsional indirect TON (TITON) alters the expression of specific proteins in the eyes and optic nerves of the rat model.
Methods :
The eyes from the previous TITON study, which induced torsional indirect TON using a robot, were used to test our hypothesis. The subjects were adult female Sprague-Dawley rats whose eyes were dissected seven days after injury. They were then sectioned and prepared through a series of washes and sublimation to be tested using MALDI IMS imaging. The mass spectra produced by MALDI from control (n=2) and TITON optic nerves (n=2) were analyzed for differences in protein expression and localization.
Results :
Preliminary mass spectra show a decrease in the intensity of protein peaks of the traumatized eyes compared to the control eyes. This suggests that TON down-regulates protein expression for at least seven days post injury. It is also suggested that changes are seen mostly in the retina and choroid of the eyes. Further testing is likely to confirm these findings and we are also optimistic that we will begin to see changes in the optic nerve as well.
Conclusions :
Our results are consistent with the hypothesis that TON produces a qualitative change in the protein expression in the rat optic nerve following TITON. Further analysis is underway to identify specific proteins whose expression is related to trauma. Identification will ultimately lead to improved understanding of the molecular mechanisms governing TON, and possibly to the development of more effective trauma therapies.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.