Retinal ganglion cell damage induced by spontaneous autoimmune optic neuritis in MOG-specific TCR transgenic mice

Guan, Yangtai; Shindler, Kenneth S.; Tabuena, Philomela; Rostami, A.M.

doi:10.1016/j.jneuroim.2006.05.019

« Previous Next »Journal of Neuroimmunology
Volume 178, Issue 1 , Pages 40-48, September 2006

Retinal ganglion cell damage induced by spontaneous autoimmune optic neuritis in MOG-specific TCR transgenic mice

Yangtai Guan
- Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA
- Department of Neurology, Shanghai Changhai Hospital, Second Military Medical University, 174 Changhai Road, Shanghai 200433, P.R. China
- Corresponding author. Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA. Tel.: +1 215 955 2583; fax: +1 215 503 5848.
Kenneth S. Shindler
- Department of Ophthalmology, University of Pennsylvania, Scheie Eye Institute, 51 N. 39th Street, Philadelphia, PA 19104, USA
- Tel.: +1 215 662 8042; fax: +1 215 243 4694.
Philomela Tabuena
- Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA
A.M. Rostami
- Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA

Received 3 February 2006; received in revised form 16 May 2006; accepted 17 May 2006. published online 10 July 2006.

Abstract

Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are marked by inflammatory demyelinating lesions throughout the central nervous system, including optic nerve. Neuronal loss also occurs in EAE, including retinal ganglion cell (RGC) loss in eyes with optic neuritis, but the finding of RGC loss in relation to optic nerve inflammation differs in different EAE settings. Recently, Myelin oligodendrocyte glycoprotein (MOG)-specific TCR transgenic mice were found to develop spontaneous isolated optic neuritis in the absence of EAE. In the current study, the relationship of inflammation to retinal ganglion cell (RGC) loss during isolated optic neuritis is examined. RGCs of MOG-specific TCR transgenic mice were labeled with Flourogold and then treated with pertussis toxin (PT) or observed untreated. At various time points, RGCs were counted, retinas were TUNEL labeled, and optic nerves were examined for inflammatory cell infiltrates. 29% of untreated MOG-specific TCR transgenic mice developed periocular inflammation by 4 months of age, and 32% of optic nerves of TCR transgenic mice had histological lesions in the optic nerve. Incidence of histological optic neuritis was 20% at day 8 following injection of PT and increased to 48% by day 12, and 68% by day 16. In contrast, no RGC loss or TUNEL staining was detected in eyes with optic neuritis until day 12 in the mice injected with PT. A 28% reduction in RGC numbers at day 12 increased to 39% by day 16, and RGC loss of eyes with severe or massive inflammation was significantly higher than that of eyes with mild or moderate inflammation. No RGC loss occurred in TCR transgenic mouse eyes without optic neuritis. The fact that inflammation precedes RGC loss suggests that neuronal loss during optic neuritis occurs secondary to the inflammatory process in isolated optic neuritis.

Keywords: Multiple sclerosis, Experimental autoimmune encephalomyelitis, Optic nerve, Optic euritis, Retinal ganglion cell, Myelin oligodendrocyte glycoprotein