Current address: Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO, USA.
Transsynaptic virus tracing from host brain to subretinal transplants
Article first published online: 10 JAN 2005
European Journal of Neuroscience
Volume 21, Issue 1, pages 161–172, January 2005
How to Cite
Seiler, M. J., Sagdullaev, B. T., Woch, G., Thomas, B. B. and Aramant, R. B. (2005), Transsynaptic virus tracing from host brain to subretinal transplants. European Journal of Neuroscience, 21: 161–172. doi: 10.1111/j.1460-9568.2004.03851.x
- Issue published online: 10 JAN 2005
- Article first published online: 10 JAN 2005
- Received 4 August 2004, revised 6 October 2004, accepted 26 October 2004
- electron microscopy;
- photoreceptor dystrophy;
- retinal degeneration;
- retinal transplantation;
- virus infection
The aim of this study was to establish synapses between a transplant and a degenerated retina. To tackle this difficult task, a little-known but well-established CNS method was chosen: trans-synaptic pseudorabies virus (PRV) tracing. Sheets of E19 rat retina with or without retinal pigment epithelium (RPE) were transplanted to the subretinal space in 33 Royal College of Surgeons (RCS) and transgenic s334ter-5 rats with retinal degeneration. Several months later, PRV-BaBlu (expressing E. coliβ-galactosidase) or PRV-Bartha was injected into an area of the exposed superior colliculus (SC), topographically corresponding to the transplant placement in the retina. Twenty normal rats served as controls. After survival times of 1–5 days, retinas were examined for virus by X-gal histochemistry, immunohistochemistry and electron microscopy. In normal controls, virus was first seen in retinal ganglion cells and Müller glia after 1–1.5 days, and had spread to all retinal layers after 2–3 days. Virus-labeled cells were found in 16 of 19 transplants where the virus injection had retrogradely labeled the topographically correct transplant area of the host retina. Electron microscopically, enveloped and nonenveloped virus could clearly be detected in infected cells. Enveloped virus was found only in neurons. Infected glial cells contained only nonenveloped virus. Neurons in retinal transplants are labeled after PRV injection into the host brain, indicating synaptic connectivity between transplants and degenerated host retinas. This study provides evidence that PRV spreads in the retina as in other parts of the CNS and is useful to outline transplant–host circuitry.