RGC and Vision Loss From Traumatic Optic Neuropathy Induced by Repetitive Closed Head Trauma Is Dependent on Timing and Force of Impact.

Autor: Khan RS; Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA., Ross AG; Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA., Aravand P; Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA., Dine K; Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA., Selzer EB; Thomas Jefferson University School of Medicine, Philadelphia, PA, USA., Shindler KS; Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Jazyk: angličtina
Zdroj: Translational vision science & technology [Transl Vis Sci Technol] 2021 Jan 06; Vol. 10 (1), pp. 8. Date of Electronic Publication: 2021 Jan 06 (Print Publication: 2021).
DOI: 10.1167/tvst.10.1.8
Abstrakt: Purpose: Traumatic optic neuropathy (TON) is often caused by blunt head trauma and has no currently effective treatment. Common animal models of TON induced by surgical crush injury are plagued by variability and do not mimic typical mechanisms of TON injury. Traumatic head impact models have recently shown evidence of TON, but the degree of head impact necessary to consistently induce TON is not well characterized, and it is examined here.
Methods: Traumatic skull impacts to C57BL/6J mice were induced using an electromagnetic controlled impact device. One impact performed at two depths (mild and severe), as well as three and five repetitive impacts with an interconcussion interval of 48 hours, were tested. Optokinetic responses (OKRs) and retinal ganglion cell (RGC) loss were measured.
Results: Five repetitive mild impacts significantly decreased OKR scores and RGC numbers compared with control mice 10 weeks after initial impact, with maximal pathology observed by 6 weeks and partial but significant loss present by 3 weeks. One severe impact induced similar TON. Three mild impacts also induced early OKR and RGC loss, but one mild impact did not. Equivalent degrees of TON were induced bilaterally, and a significant correlation was observed between OKR scores and RGC numbers.
Conclusions: Repetitive, mild closed head trauma in mice induces progressive RGC and vision loss that worsens with increasing impacts.
Translational Relevance: Results detail a reproducible model of TON that provides a reliable platform for studying potential treatments over a 3- to 6-week time course.
Competing Interests: Disclosure: R.S. Khan, None; A.G. Ross, None; P. Aravand, None; K. Dine, None; E.B. Selzer, None; K.S. Shindler, None
(Copyright 2021 The Authors.)
Databáze: MEDLINE