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M.J. Seiler, B.B. Thomas, Z. Chen, R. Wu, S.R. Sadda, R.B. Aramant; Retinal Transplants Restore Visual Responses – Transsynaptic Tracing From Visually Responsive Site in the Superior Colliculus (SC) Labels Transplant Neurons . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4164.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To demonstrate that visual responses in the SC are due to synaptic connections between fetal retinal transplants and degenerating host retinas. Methods: Sheets of E19 rat retina expressing human alkaline phosphatase (hPAP) were transplanted to the subretinal space of 3–4 week old transgenic S334ter–3 rats with fast retinal degeneration. Several months after transplantation, visual responses were recorded from the SC of transplanted rats. Then, the attenuated pseudorabies virus strains PRV–152 (expressing GFP) or BaBlu (expressing E. coli ß–galactosidase) were injected into the visually responsive site in the SC. These viruses are specifically transferred between neurons at synapses. After survival times of 1–2 days, the virus was detected in the retina by immunohistochemistry, in combination with different retinal cell markers, such as PKC, recoverin, calbindin, CaMK–II, and glutamine synthetase. Results: Transplant rats selected for virus tracing had response thresholds of –2.20 to –2.80 log cd/m2 in a small area of the SC corresponding to the retinal transplant placement. Such responses could not be found in non–transplanted transgenic rats (see abstract by Thomas et al.). In all experiments, the injection traced back to ganglion cells overlying the transplant or in close proximity to the transplant. Thirty hours after virus injection, few ganglion cells were labeled in this area. At survival times of 2 days, heavy virus label was found in the host retina, and many cells in the transplant were also labeled. Virus–labeled cells in the transplant were double–labeled for NeuN, Parvalbumin, CaMK–II and glutamine synthetase, indicating that both neurons and glial cells were labeled. Conclusions: This study provides anatomical evidence that synaptic connections between fetal retinal transplants and host retinas are involved in the restoration of visual responses in the SC.
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