Transsynaptic virus tracing from host brain to subretinal transplants

Area of Science:

• Neuroscience
• Ophthalmology
• Regenerative Medicine

Background:

• Retinal degeneration leads to vision loss.
• Establishing functional connections between retinal transplants and host retinas is crucial for vision restoration.
• Trans-synaptic tracing offers a method to assess neural connectivity.

Purpose of the Study:

• To establish and verify synaptic connections between retinal transplants and degenerated host retinas.
• To evaluate the utility of trans-synaptic pseudorabies virus (PRV) tracing in assessing retinal circuitry.
• To demonstrate the spread and utility of PRV in retinal tissue.

Main Methods:

• Transplantation of E19 rat retina sheets into Royal College of Surgeons (RCS) and transgenic s334ter-5 rats with retinal degeneration.
• Injection of PRV-BaBlu or PRV-Bartha into the superior colliculus (SC) of host rats.
• Histochemical, immunohistochemical, and electron microscopic analysis of retinas to detect viral spread and infected cells.

Main Results:

• PRV-labeled cells were identified in 16 out of 19 retinal transplants, indicating successful retrograde labeling.
• Virus spread within the retina followed a pattern similar to other central nervous system (CNS) tissues.
• Electron microscopy confirmed the presence of enveloped virus in neurons and nonenveloped virus in glial cells.

Conclusions:

• Neurons within retinal transplants form synaptic connections with the degenerated host retina.
• Trans-synaptic PRV tracing is an effective method for mapping neural circuitry in retinal transplants.
• This technique provides evidence for successful integration and functional connectivity of retinal grafts.