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

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Abstract

Background

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 Müller 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.

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Acknowledgements

The authors extend their gratitude to Karin Arnér, Jill Barnes, Bruce Collins, Donna Hardin and Jeff Sommer.

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Authors and Affiliations

  1. Department of Ophthalmology, BMC, Lund University Hospital, 22184, Lund, Sweden

    Fredrik Ghosh & Karl Engelsberg

  2. College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA

    Robert V. English

  3. Department of Animal Science, North Carolina State University, Raleigh, NC, USA

    Robert M. Petters

Authors
  1. Fredrik Ghosh
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  2. Karl Engelsberg
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  3. Robert V. English
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  4. Robert M. Petters
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Corresponding author

Correspondence to Fredrik Ghosh.

Additional information

Supported by The Foundation Fighting Blindness (grant# C-NC02-798-0078), The Faculty of Medicine, University of Lund, The Swedish Research Council, The Princess Margaretas Foundation for Blind Children, The 2nd ONCE International Award for New Technologies for the Blind.

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Ghosh, F., Engelsberg, K., English, R.V. et al. Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa. Graefe's Arch Clin Exp Ophthalmol 245, 835–846 (2007). https://doi.org/10.1007/s00417-006-0437-9

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  • DOI: https://doi.org/10.1007/s00417-006-0437-9

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