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Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa.

Ghosh, Fredrik LU ; Engelsberg, Karl LU ; English, Robert and Petters, Robert (2007) In Graefe's Archive for Clinical and Experimental Ophthalmology 245(6). p.835-846
Abstract
The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Muller cells were found in five of six eyes. Neuronal connections between... (More)
The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Muller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Conclusions Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
immune privilege, retinal degeneration, photoreceptor morphology, vitreoretinal surgery
in
Graefe's Archive for Clinical and Experimental Ophthalmology
volume
245
issue
6
pages
835 - 846
publisher
Springer
external identifiers
  • wos:000246594000010
  • scopus:34249296671
ISSN
1435-702X
DOI
10.1007/s00417-006-0437-9
language
English
LU publication?
yes
id
86987cdc-6e7a-42f1-9da8-980185b34956 (old id 163560)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17072635&dopt=Abstract
date added to LUP
2007-07-13 14:11:44
date last changed
2017-01-01 06:39:02
@article{86987cdc-6e7a-42f1-9da8-980185b34956,
  abstract     = {The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Muller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Conclusions Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration.},
  author       = {Ghosh, Fredrik and Engelsberg, Karl and English, Robert and Petters, Robert},
  issn         = {1435-702X},
  keyword      = {immune privilege,retinal degeneration,photoreceptor morphology,vitreoretinal surgery},
  language     = {eng},
  number       = {6},
  pages        = {835--846},
  publisher    = {Springer},
  series       = {Graefe's Archive for Clinical and Experimental Ophthalmology},
  title        = {Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa.},
  url          = {http://dx.doi.org/10.1007/s00417-006-0437-9},
  volume       = {245},
  year         = {2007},
}