A New Mouse Model of Inducible, Chronic Retinal Ganglion Cell Dysfunction Not Associated with Cell Death
Year: 2013
Type: article
Abstract: PURPOSE: To develop a mouse model of inducible, chronic retinal ganglion cell (RGC) dysfunction not associated with cell death. METHODS: Eighteen C57BL/6J mice were longitudinally tested with pattern electroretinogram (PERG) and spectral-domain optical coherence tomography (OCT) before and after aspiration of the contralateral superior colliculus (SC), which removed terminals of optic tract axons and the superficial layers of the SC. At the 4-month end points, retinas were harvested for Brn3b immunostaining and BDNF immunoblotting. RESULTS: The PERG lost approximately 60% of its baseline amplitude (P < 0.01) within the first day after lesion, and remained at a reduced level over 4 months. At the end point, the density of Brn3b-positive RGCs was normal, but their nucleus size was reduced by approximately 24% (P < 001). OCT measurements showed thinning of the inner, but not outer, retina by approximately 9% (P < 0.01) starting 10 to 20 days after lesion. Retinal nerve fiber layer thickness was unchanged. At the end point, retinal homogenates showed a substantial overexpression of BDNF protein level. CONCLUSIONS: Mechanical SC lesion in adult mice results in a rapid, chronic loss of RGC electrical responsiveness that is followed by cell shrinkage but not cell death. The SC-lesion mouse represents a new, inducible model that allows investigating stages and mechanisms of RGC dysfunction without the confounding effects of cell death that are common in the existing models of optic neuropathies and optic nerve lesions.
Authors: Xu Yang, Tsung-Han Chou, Marco Ruggeri, Vittorio Porciatti
Institutions: University of Miami, University of Miami Health System
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Eye Institute
Awards: G418665955, G721603795
OpenAlex ID: W2068865626