Skip to main content

Advertisement

SpringerLink
Log in

Preservation of photoreceptors in dystrophic RCS rats following allo- and xenotransplantation of IPE cells

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

Abstract

Purpose

To examine whether iris pigment epithelial (IPE) cells transplanted into the subretinal space of Royal College of Surgeons (RCS) rats have the ability to rescue photoreceptors.

Methods

Rat IPE (rIPE) or human IPE (hIPE) cells were transplanted subretinally in 23-day-old RCS rats. Sham injection and transplantation of ARPE-19 cells served as controls. After 12 weeks, eyes were evaluated for photoreceptor survival by morphometric analysis and electron microscopy.

Results

Morphometric analysis showed photoreceptor rescue in all transplanted and sham-injected animals (number of photoreceptors/300 µm retina±sd: rIPE 41.67 ± 28; hIPE 29.50 ± 16; ARPE-19 36.12 ± 21; sham 16.56 ± 6) compared to age-matched, control rats (number of photoreceptors/300 µm retina±sd: 9.71 ± 4). Photoreceptor rescue was prominent in IPE cell-transplanted rats and was significantly greater than sham-injected eyes (p = 0.02 for rIPE and p = 0.04 for hIPE).

Conclusion

Since IPE cells transplanted into the subretinal space have the ability to rescue photoreceptors from degeneration in the RCS rat without any harmful effects, IPE cells may represent an ideal cell to genetically modify and thus carry essential genetic information for the repair of defects in the subretinal space.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Eckardt C, Eckardt U, Conrad HG (1999) Macular rotation with and without counter-rotation of the globe in patients with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 237:313–325, doi:10.1007/s004170050239

    Article  PubMed  CAS  Google Scholar 

  2. Steinhorst UH, Kuster S (1997) Surgical treatment of senile macular degeneration: rotation or transplantation? Klin Monatsbl Augenheilkd 210:aA1–aA2

    PubMed  CAS  Google Scholar 

  3. Terasaki H, Miyake Y, Suzuki T, Niwa T, Piao CH, Suzuki S et al (2002) Change in full-field ERGs after macular translocation surgery with 360 degrees retinotomy. Invest Ophthalmol Vis Sci 43:452–457

    PubMed  Google Scholar 

  4. Aisenbrey S, Lafaut BA, Szurman P, Grisanti S, Luke C, Krott R et al (2002) Macular translocation with 360 degrees retinotomy for exudative age-related macular degeneration. Arch Ophthalmol 120:451–459

    PubMed  Google Scholar 

  5. Aisenbrey S, Bartz-Schmidt U (2003) Macular translocation with 360-degree retinotomy for management of age-related macular degeneration with subfoveal choroidal neovascularization. Am J Ophthalmol 135:748–749, doi:10.1016/S0002-9394(03)00145-4

    Article  PubMed  Google Scholar 

  6. Aisenbrey S, Bartz-Schmidt KU, Walter P, Hilgers RD, Ayertey H, Szurman P et al (2007) Long-term follow-up of macular translocation with 360 degrees retinotomy for exudative age-related macular degeneration. Arch Ophthalmol 125:1367–1372, doi:10.1001/archopht.125.10.1367

    Article  PubMed  Google Scholar 

  7. Abe T, Yoshida M, Kano T, Tamai M (2001) Visual function after removal of subretinal neovascular membranes in patients with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 239:927–936, doi:10.1007/s00417-001-0393-3

    Article  PubMed  CAS  Google Scholar 

  8. Aisenbrey S, Lafaut BA, Szurman P, Hilgers RD, Esser P, Walter P et al (2006) Iris pigment epithelial translocation in the treatment of exudative macular degeneration: a 3-year follow-up. Arch Ophthalmol 124:183–188, doi:10.1001/archopht.124.2.183

    Article  PubMed  Google Scholar 

  9. Algvere PV, Gouras P, Dafgard KE (1999) Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD. Eur J Ophthalmol 9:217–230

    PubMed  CAS  Google Scholar 

  10. Binder S, Krebs I, Hilgers RD, Abri A, Stolba U, Assadoulina A et al (2004) Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial. Invest Ophthalmol Vis Sci 45:4151–4160, doi:10.1167/iovs.04-0118

    Article  PubMed  Google Scholar 

  11. van Meurs JC, ter Averst E, Hofland LJ, van Hagen PM, Mooy CM, Baarsma GS et al (2004) Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes. Br J Ophthalmol 88:110–113, doi:10.1136/bjo.88.1.110

    Article  PubMed  Google Scholar 

  12. Lawrence JM, Sauve Y, Keegan DJ, Coffey PJ, Hetherington L, Girman S et al (2000) Schwann cell grafting into the retina of the dystrophic RCS rat limits functional deterioration. Invest Ophthalmol Vis Sci 41:518–528

    PubMed  CAS  Google Scholar 

  13. Lawrence JM, Keegan DJ, Muir EM, Coffey PJ, Rogers JH, Wilby MJ et al (2004) Transplantation of Schwann cell line clones secreting GDNF or BDNF into the retinas of dystrophic Royal College of Surgeons rats. Invest Ophthalmol Vis Sci 45:267–274, doi:10.1167/iovs.03-0093

    Article  PubMed  Google Scholar 

  14. McGill TJ, Lund RD, Douglas RM, Wang S, Lu B, Silver BD et al (2007) Syngeneic Schwann cell transplantation preserves vision in RCS rat without immunosuppression. Invest Ophthalmol Vis Sci 48:1906–1912, doi:10.1167/iovs.06-1117

    Article  PubMed  Google Scholar 

  15. Wang S, Lu B, Wood P, Lund RD (2005) Grafting of ARPE-19 and Schwann cells to the subretinal space in RCS rats. Invest Ophthalmol Vis Sci 46:2552–2560, doi:10.1167/iovs.05-0279

    Article  PubMed  Google Scholar 

  16. Inoue Y, Iriyama A, Ueno S, Takahashi H, Kondo M, Tamaki Y et al (2007) Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration. Exp Eye Res 85:234–241, doi:10.1016/j.exer.2007.04.007

    Article  PubMed  CAS  Google Scholar 

  17. Wang S, Girman S, Lu B, Bischoff N, Holmes T, Shearer R et al (2008) Long-term vision rescue by human neural progenitors in a rat model of photoreceptor degeneration. Invest Ophthalmol Vis Sci 49:3201–3206, doi:10.1167/iovs.08-1831

    Article  PubMed  Google Scholar 

  18. Wang S, Lu B, Girman S, Holmes T, Bischoff N, Lund RD (2008) Morphological and functional rescue in RCS rats after RPE cell line transplantation at a later stage of degeneration. Invest Ophthalmol Vis Sci 49:416–421, doi:10.1167/iovs.07-0992

    Article  PubMed  Google Scholar 

  19. Pinilla I, Cuenca N, Sauve Y, Wang S, Lund RD (2007) Preservation of outer retina and its synaptic connectivity following subretinal injections of human RPE cells in the Royal College of Surgeons rat. Exp Eye Res 85:381–392, doi:10.1016/j.exer.2007.06.002

    Article  PubMed  CAS  Google Scholar 

  20. Gias C, Jones M, Keegan D, Adamson P, Greenwood J, Lund R et al (2007) Preservation of visual cortical function following retinal pigment epithelium transplantation in the RCS rat using optical imaging techniques. Eur J Neurosci 25:1940–1948, doi:10.1111/j.1460-9568.2007.05459.x

    Article  PubMed  Google Scholar 

  21. Lund RD, Wang S, Klimanskaya I, Holmes T, Ramos-Kelsey R, Lu B et al (2006) Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells 8:189–199, doi:10.1089/clo.2006.8.189

    Article  PubMed  CAS  Google Scholar 

  22. Abe T, Yoshida M, Tomita H, Kano T, Sato M, Wada Y et al (2000) Auto iris pigment epithelial cell transplantation in patients with age- related macular degeneration: short-term results. Tohoku J Exp Med 191:7–20, doi:10.1620/tjem.191.7

    Article  PubMed  CAS  Google Scholar 

  23. Lappas A, Weinberger AW, Foerster AM, Kube T, Rezai KA, Kirchhof B (2000) Iris pigment epithelial cell translocation in exudative age-related macular degeneration. A pilot study in patients. Graefes Arch Clin Exp Ophthalmol 238:631–641, doi:10.1007/s004170000149

    Article  PubMed  CAS  Google Scholar 

  24. Lappas A, Foerster AM, Weinberger AW, Coburger S, Schrage NF, Kirchhof B (2004) Translocation of iris pigment epithelium in patients with exudative age-related macular degeneration: long-term results. Graefes Arch Clin Exp Ophthalmol 242:638–647, doi:10.1007/s00417-003-0764-z

    Article  PubMed  Google Scholar 

  25. Thumann G, Aisenbrey S, Schraermeyer U, Lafaut B, Esser P, Walter P et al (2000) Transplantation of autologous iris pigment epithelium after removal of choroidal neovascular membranes. Arch Ophthalmol 118:1350–1355

    PubMed  CAS  Google Scholar 

  26. Schraermeyer U, Kociok N, Heimann K (1999) Rescue effects of IPE transplants in RCS rats: short-term results. Invest Ophthalmol Vis Sci 40:1545–1556

    PubMed  CAS  Google Scholar 

  27. Michon JJ, Li ZL, Shioura N, Anderson RJ, Tso MO (1991) A comparative study of methods of photoreceptor morphometry. Invest Ophthalmol Vis Sci 32:280–284

    PubMed  CAS  Google Scholar 

  28. Lenzi L, Coassin M, Lambiase A, Bonini S, Amendola T, Aloe L (2005) Effect of exogenous administration of nerve growth factor in the retina of rats with inherited retinitis pigmentosa. Vision Res 45:1491–1500, doi:10.1016/j.visres.2004.12.020

    Article  PubMed  CAS  Google Scholar 

  29. Perry J, Du J, Kjeldbye H, Gouras P (1995) The effects of bFGF on RCS rat eyes. Curr Eye Res 14:585–592, doi:10.3109/02713689508998406

    Article  PubMed  CAS  Google Scholar 

  30. Sakai T, Kuno N, Takamatsu F, Kimura E, Kohno H, Okano K et al (2007) Prolonged protective effect of basic fibroblast growth factor-impregnated nanoparticles in Royal College of Surgeons rats. Invest Ophthalmol Vis Sci 48:3381–3387, doi:10.1167/iovs.06-1242

    Article  PubMed  Google Scholar 

  31. Caffe AR, Soderpalm AK, Holmqvist I, van Veen T (2001) A combination of CNTF and BDNF rescues rd photoreceptors but changes rod differentiation in the presence of RPE in retinal explants. Invest Ophthalmol Vis Sci 42:275–282

    PubMed  CAS  Google Scholar 

  32. Whiteley SJ, Klassen H, Coffey PJ, Young MJ (2001) Photoreceptor rescue after low-dose intravitreal IL-1beta injection in the RCS rat. Exp Eye Res 73:557–568, doi:10.1006/exer.2001.1066

    Article  PubMed  CAS  Google Scholar 

  33. Carwile ME, Culbert RB, Sturdivant RL, Kraft TW (1998) Rod outer segment maintenance is enhanced in the presence of bFGF, CNTF and GDNF. Exp Eye Res 66:791–805, doi:10.1006/exer.1998.0488

    Article  PubMed  CAS  Google Scholar 

  34. McGee Sanftner LH, Abel H, Hauswirth WW, Flannery JG (2001) Glial cell line derived neurotrophic factor delays photoreceptor degeneration in a transgenic rat model of retinitis pigmentosa. Mol Ther 4:622–629, doi:10.1006/mthe.2001.0498

    Article  PubMed  CAS  Google Scholar 

  35. Kent TL, Glybina IV, Abrams GW, Iezzi R (2008) Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat. Invest Ophthalmol Vis Sci 49:372–379, doi:10.1167/iovs.07-0952

    Article  PubMed  Google Scholar 

  36. Li LX, Turner JE (1988) Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation. Exp Eye Res 47:911–917, doi:10.1016/0014-4835(88)90073-5

    Article  PubMed  CAS  Google Scholar 

  37. Lopez R, Gouras P, Kjeldbye H, Sullivan B, Reppucci V, Brittis M et al (1989) Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat. Invest Ophthalmol Vis Sci 30:586–588

    PubMed  CAS  Google Scholar 

  38. Sheedlo HJ, Gaur V, Li LX, Seaton AD, Turner JE (1991) Transplantation to the diseased and damaged retina. Trends Neurosci 14:347–350, doi:10.1016/0166-2236(91)90160-V

    Article  PubMed  CAS  Google Scholar 

  39. Sheedlo HJ, Li L, Gaur VP, Young RW, Seaton AD, Stovall SV et al (1992) Photoreceptor rescue in the dystrophic retina by transplantation of retinal pigment epithelium. Int Rev Cytol 138:1–49, doi:10.1016/S0074-7696(08)61586-7

    Article  PubMed  CAS  Google Scholar 

  40. Klassen H, Whiteley SJ, Young MJ, Lund RD (2001) Graft location affects functional rescue following RPE cell transplantation in the RCS rat. Exp Neurol 169:114–121, doi:10.1006/exnr.2000.7617

    Article  PubMed  CAS  Google Scholar 

  41. Sauve Y, Klassen H, Whiteley SJ, Lund RD (1998) Visual field loss in RCS rats and the effect of RPE cell transplantation. Exp Neurol 152:243–250, doi:10.1006/exnr.1998.6849

    Article  PubMed  CAS  Google Scholar 

  42. Kociok N, Heppekausen H, Schraermeyer U, Esser P, Thumann G, Grisanti S et al (1998) The mRNA expression of cytokines and their receptors in cultured iris pigment epithelial cells: a comparison with retinal pigment epithelial cells. Exp Eye Res 67:237–250, doi:10.1006/exer.1998.0517

    Article  PubMed  CAS  Google Scholar 

  43. Thumann G, Kociok N, Bartz-Schmidt KU, Esser P, Schraermeyer U, Heimann K (1999) Detection of mRNA for proteins involved in retinol metabolism in iris pigment epithelium. Graefes Arch Clin Exp Ophthalmol 237:1046–1051, doi:10.1007/s004170050343

    Article  PubMed  CAS  Google Scholar 

  44. Schraermeyer U, Enzmann V, Kohen L, Addicks K, Wiedemann P, Heimann K (1997) Porcine iris pigment epithelial cells can take up retinal outer segments. Exp Eye Res 65:277–287, doi:10.1006/exer.1997.0339

    Article  PubMed  CAS  Google Scholar 

  45. Rezai KA, Lappas A, Farrokh-Siar L, Kohen L, Wiedemann P, Heimann K (1997) Iris pigment epithelial cells of Long–Evans rats demonstrate phagocytic activity. Exp Eye Res 65:23–29, doi:10.1006/exer.1997.0307

    Article  PubMed  CAS  Google Scholar 

  46. Thumann G, Bartz-Schmidt KU, Heimann K, Schraermeyer U (1998) Phagocytosis of rod outer segments by human iris pigment epithelial cells in vitro. Graefes Arch Clin Exp Ophthalmol 236:753–757, doi:10.1007/s004170050154

    Article  PubMed  CAS  Google Scholar 

  47. Crafoord S, Geng L, Seregard S, Algvere PV (2002) Photoreceptor survival in transplantation of autologous iris pigment epithelial cells to the subretinal space. Acta Ophthalmol Scand 80:387–394, doi:10.1034/j.1600-0420.2002.800408.x

    Article  PubMed  Google Scholar 

  48. Thumann G, Bartz-Schmidt KU, El Bakri H, Schraermeyer U, Spee C, Cui JZ et al (1999) Transplantation of autologous iris pigment epithelium to the subretinal space in rabbits. Transplantation 68:195–201, doi:10.1097/00007890-199907270-00006

    Article  PubMed  CAS  Google Scholar 

  49. Sauve Y, Pinilla I, Lund RD (2006) Partial preservation of rod and cone ERG function following subretinal injection of ARPE-19 cells in RCS rats. Vision Res 46:1459–1472, doi:10.1016/j.visres.2005.11.009

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Interdisciplinary Centre for Clinical Research “BIOMAT” within the Faculty of Medicine at the RWTH University of Aachen.

Author information

Authors and Affiliations

  1. IZKF “Biomat”, RWTH University of Aachen, Pauwelsstraße 30, 52074, Aachen, Germany

    Gabriele Thumann, Anna Katharina Salz & Sandra Johnen

  2. Department of Ophthalmology, RWTH University of Aachen, Pauwelsstraße 30, 52074, Aachen, Germany

    Gabriele Thumann & Peter Walter

Authors
  1. Gabriele Thumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Katharina Salz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Walter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sandra Johnen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriele Thumann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thumann, G., Salz, A.K., Walter, P. et al. Preservation of photoreceptors in dystrophic RCS rats following allo- and xenotransplantation of IPE cells. Graefes Arch Clin Exp Ophthalmol 247, 363–369 (2009). https://doi.org/10.1007/s00417-008-0998-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-008-0998-x

Keywords

Search

Navigation