Citation

Dutca L, Stasheff SF, Hedberg-Buenz A, Rudd DS, Batra N, Blodi FR, Yorek MS, Yin T, Shankar M, Herlein J, Naidoo J, Morlock L, Williams N, Kardon RH, Anderson M, Pieper A, Harper MM. Invest. Ophthalmol. Vis. Sci. 2014; 55(12): 8330-8341.

Affiliation

Center for the Prevention and Treatment of Visual Loss, Department of Veterans Affairs, 601 Hwy 6 W, Iowa City, IA, 52242, United States matthew-harper@uiowa.edu.

Copyright

(Copyright © 2014, Association for Research in Vision and Ophthalmology)

DOI

10.1167/iovs.14-15468

PMID

25468886

Abstract

PURPOSE: TBI frequently leads to visual dysfunction. The purpose of this study was to investigate the effect of TBI on RGCs, and to test whether treatment with the novel neuroprotective compound P7C3-S243 could prevent functional deficits in the visual system.

METHODS: Blast-mediated TBI was induced in a blast chamber. RGC physiology was evaluated using a multi-electrode array and pattern electroretinogram (PERG). Analysis of RGC dendritic field and number were evaluated at the end of the study. Visual outcome measures were also evaluated based on treatment of mice with P7C3-S243 or vehicle control.

RESULTS Deficits in PERG after TBI occur in a temporally bimodal fashion, with temporary recovery 4 weeks after injury followed by chronically persistent dysfunction 12 weeks later. This later time point is associated with dendritic abnormalities and death of RGCs. We also demonstrate that ongoing pathologic processes during the temporary recovery latent period (including abnormalities of RGC physiology) lead to future dysfunction of the visual system. We report that modification of PERG to provocative postural tilt testing elicits changes in PERG measurements that correlate with a key in vitro measures of damage: the spontaneous and light-evoked activity of RGCs.

CONCLUSIONS: Provocative PERG testing serves as a non-invasive test in the living organism to identify early damage to the visual system, which may reflect corresponding damage in the brain that is not otherwise detectable by noninvasive means. Treatment with P7C3-S243 immediately after injury and throughout the temporary recovery latent period protects mice from developing chronic visual system dysfunction.

Language: en