Movatterモバイル変換

[0]ホーム
URL:

Skip to main content

Advertisement

Springer Nature Link
Log in

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

  • Laboratory Investigation
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

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.

This is a preview of subscription content,log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
¥17,985 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Japan)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Arai S, Thomas BB, Seiler MJ, Aramant RB, Qiu G, Mui C, de Juan E, Sadda SR (2004) Restoration of visual responses following transplantation of intact retinal sheets in rd mice. Exp Eye Res 79:331–341

    Article PubMed CAS  Google Scholar 

  2. Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Dryja TP (1991) Ocular findings in patients with autosomal dominant retinitis pigmentosa and rhodopsin, proline-347-leucine. Am J Ophthalmol 15:614–623

    Google Scholar 

  3. Brundin P, Karlsson J, Emgard M, Schierle GS, Hansson O, Petersen A, Castilho RF (2000) Improving the survival of grafted dopaminergic neurons: a review over current approaches. Cell Transplant 9:179–195

    PubMed CAS  Google Scholar 

  4. Cideciyan AV, Jacobson SG, Aleman TS, Gu D, Pearce-Kelling SE, Sumaroka A, Acland GM, Aguirre GD (2005) In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa. Proc Natl Acad Sci USA 102:5233–5238

    Article PubMed CAS  Google Scholar 

  5. Cook B, Lewis GP, Fisher SK, Adler R (1995) Apoptotic photoreceptor degeneration in experimental retinal detachment. Invest Ophthalmol Vis Sci 36:990–996

    PubMed CAS  Google Scholar 

  6. Das T, del Cerro M, Jalali S, Rao VS, Gullapalli VK, Little C, Loreto DA, Sharma S, Sreedharan A, del Cerro C, Rao GN (1999) The transplantation of human fetal neuroretinal cells in advanced retinitis pigmentosa patients: results of a long-term safety study. Exp Neurol 157:58–68

    Article PubMed CAS  Google Scholar 

  7. De Schaepdrijver L, Simoens P, Lauwers H, De Geest JP (1989) Retinal vascular patterns in domestic animals. Res Vet Sci 47:34–42

    PubMed  Google Scholar 

  8. Emgard M, Blomgren K, Brundin P (2002) Characterisation of cell damage and death in embryonic mesencephalic tissue: a study on ultrastructure, vital stains and protease activity. Neuroscience 115:1177–1187

    Article PubMed CAS  Google Scholar 

  9. Engelsberg K, Johansson K, Ghosh F (2005) Development of the embryonic porcine neuroretina in vitro. Ophthalmic Res 37:104–111

    Article PubMed  Google Scholar 

  10. Fisher SK, Lewis GP (2003) Müller cell and neuronal remodeling in retinal detachment and reattachment and their potential consequences for visual recovery: a review and reconsideration of recent data. Vision Res 43:887–897

    Article PubMed  Google Scholar 

  11. Ghosh F, Arnér K, Ehinger B (1998) Transplant of full-thickness embryonic rabbit retina using pars plana vitrectomy. Retina 18:136–142

    PubMed CAS  Google Scholar 

  12. Ghosh F, Bruun A, Ehinger B (1999) Graft-host connections in long-term full thickness embryonic rabbit retinal transplants. Invest Ophthalmol Vis Sci 40:126–132

    PubMed CAS  Google Scholar 

  13. Ghosh F, Johansson K, Ehinger B (1999) Long-term full-thickness embryonic rabbit retinal transplants. Invest Ophthalmol Vis Sci 40:133–140

    PubMed CAS  Google Scholar 

  14. Ghosh F, Bruun A, Ehinger B (1999) Immunohistochemical markers in well laminated retinal transplants. Ophthalmic Res 31:5–15

    Article PubMed CAS  Google Scholar 

  15. Ghosh F, Arnér K (2002) Transplantation of full-thickness retina in the normal porcine eye-surgical and morphological aspects. Retina 22:478–486

    Article PubMed  Google Scholar 

  16. Ghosh F, Wong F, Johansson K, Bruun A, Petters RM (2004) Transplantation of full-thickness retina in the rhodopsin transgenic pig. Retina 24:98–109

    Article PubMed  Google Scholar 

  17. Gouras P, Du J, Kjeldbye H, Yamamamoto S, Zack DJ (1994) Long-term photoreceptor transplants in dystrophic and normal mouse retina. Invest Ophthalmol Vis Sci 35:3145–3153

    PubMed CAS  Google Scholar 

  18. Hayreh SS, Kolder HE, Weingeist TA (1980) Central retinal artery occlusion and retinal tolerance time. Ophthalmology 87:75–78

    PubMed CAS  Google Scholar 

  19. Jackson TL, Hillenkamp J, Williamson TH, Clarke KW, Almubarak AI, Marshall J (2003) An experimental model of rhegmatogenous retinal detachment: surgical results and glial cell response. Invest Ophthalmol Vis Sci 44:4026–4034

    Article PubMed  Google Scholar 

  20. Jones BW, Watt CB, Frederick JM, Baehr W, Chen CK, Levine EM, Milam AH, Lavail MM, Marc RE (2003) Retinal remodeling triggered by photoreceptor degenerations. J Comp Neurol 464:1–16

    Article PubMed  Google Scholar 

  21. Kwan AS, Wang S, Lund RD (1999) Photoreceptor layer reconstruction in a rodent model of retinal degeneration. Exp Neurol 159:21–33

    Article PubMed CAS  Google Scholar 

  22. Li ZY, Wong F, Chang JH, Possin DE, Hao Y, Petters RM, Milam AH (1998) Rhodopsin transgenic pigs as a model for human retinitis pigmentosa. Invest Ophthalmol Vis Sci 39:808–819

    PubMed CAS  Google Scholar 

  23. Lund RD, Kwan AS, Keegan DJ, Sauve Y, Coffey PJ, Lawrence JM (2001) Cell transplantation as a treatment for retinal disease. Prog Retin Eye Res 20:415–449

    Article PubMed CAS  Google Scholar 

  24. Mohand-Said S, Hicks D, Dreyfus H, Sahel JA (2000) Selective transplantation of rods delays cone loss in a retinitis pigmentosa model. Arch Ophthalmol 118:807–811

    PubMed CAS  Google Scholar 

  25. Petters RM, Alexander CA, Wells KD, Collins EB, Sommer JR, Blanton MR, Rojas G, Hao Y, Flowers WL, Banin E, Cideciyan AV, Jacobson SG, Wong F (1997) Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa. Nat Biotechnol 15:965–970

    Article PubMed CAS  Google Scholar 

  26. Radner W, Sadda SR, Humayun MS, Suzuki S, Melia M, Weiland J, de Juan E Jr (2001) Light-driven retinal ganglion cell responses in blind rd mice after neural retinal transplantation. Invest Ophthalmol Vis Sci 42:1057–1065

    PubMed CAS  Google Scholar 

  27. Radtke ND, Aramant RB, Seiler MJ, Petry HM, Pidwell D (2004) Vision change after sheet transplant of fetal retina with retinal pigment epithelium to a patient with retinitis pigmentosa. Arch Ophthalmol 122:1159–1165

    Article PubMed  Google Scholar 

  28. Seiler MJ, Sagdullaev BT, Woch G, Thomas BB, Aramant RB (2005) Transsynaptic virus tracing from host brain to subretinal transplants. Eur J Neurosci 21:161–172

    Article PubMed  Google Scholar 

  29. Sharma RK, Bergstrom A, Zucker CL, Adolph AR, Ehinger B (2000) Survival of long-term retinal cell transplants. Acta Ophthalmol 78:396–402

    Article CAS  Google Scholar 

  30. Turner JE, Blair JR (1986) Newborn rat retinal cells transplanted into a retinal lesion site in adult host eyes. Brain Res 391:91–104

    PubMed CAS  Google Scholar 

  31. Wassélius J, Ghosh F (2001) Adult rabbit retinal transplants. Invest Ophthalmol Vis Sci 42:2632–2638

    PubMed  Google Scholar 

  32. Woch G, Aramant RB, Seiler MJ, Sagdullaev BT, McCall MA (2001) Retinal transplants restore visually evoked responses in rats with photoreceptor degeneration. Invest Ophthalmol Vis Sci 42:1669–1676

    PubMed CAS  Google Scholar 

  33. Yoshida A, Ishiguro S, Tamai M (1993) Expression of glial fibrillary acidic protein in rabbit Muller cells after lensectomy-vitrectomy. Invest Ophthalmol Vis Sci 34:3154–3160

    PubMed CAS  Google Scholar 

Download references

Acknowledgements

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

Author information

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

    You can also search for this author inPubMed Google Scholar

  2. Karl Engelsberg

    You can also search for this author inPubMed Google Scholar

  3. Robert V. English

    You can also search for this author inPubMed Google Scholar

  4. Robert M. Petters

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toFredrik 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.

Rights and permissions

About this article

Cite this article

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 Ophthalmol245, 835–846 (2007). https://doi.org/10.1007/s00417-006-0437-9

Download citation

Keywords

Access this article

Subscribe and save

Springer+ Basic
¥17,985 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Japan)

Instant access to the full article PDF.

Advertisement

[8]ページ先頭
©2009-2025 Movatter.jp