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M.J. Seiler, B.T. Sagdullaev, G. Woch, R.B. Aramant; Tracing With Pseudorabies Virus Shows Synaptic Connectivity of Retinal Transplants With Degenerated Host Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):490.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To demonstrate synaptic connections between fetal retinal transplants and host retinas with photoreceptor degeneration (RCS and transgenic s334ter rats). Methods: Sheets of E19 rat retina with or without retinal pigment epithelium (RPE) were transplanted to the subretinal space. The position of the transplant in the retina was determined by funduscopy. Several months after transplantation, 33 transplanted rats and 20 normal controls were injected into the superior colliculus with the attenuated pseudorabies virus strains BaBlu (expressing E. coli ß-galactosidase) or Bartha. The injection sites were estimated to correspond topographically to the transplant area in the retina. After survival times of 1-3 days, the virus was detected in the retina by X-gal histochemistry, immunohistochemistry, and electron microscopy. Results: In normal controls, the virus was first seen in retinal ganglion cells and Müller glia. With survival times of 2-3 days, the virus was found in all retinal layers. With longer survival times, the virus-labeled area increased laterally. In 21 of 33 transplanted rats, the virus was found in the host retina overlaying the transplant, whereas this target was missed in 12 experiments. In 17 of these 21 experiments, virus-labeled cells were found in the transplants. One rat contained no virus labeled cells in the retina because of optic nerve damage. In the electron microscope, virus-infected cells were characterized by a punctate pattern of chromatin in the nucleus. In normal and in transplanted retina, enveloped virus was found only in neuronal cells. Infected glial cells contained only non-enveloped virus. Conclusions: This study provides anatomical evidence that fetal retinal transplants form synaptic connections with degenerated host retinas. Strategies are currently being developed to improve this connectivity. Supported by NIH grant EY08519; the Foundation Fighting Blindness; The Kentucky Lions Eye Foundation; an unrestricted grant from the Research to Prevent Blindness; and anonymous sponsor.
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