HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (38) Citing Articles via Google Scholar Google Scholar Articles by Lawrence, J. M. Articles by Lund, R. D. Search for Related Content PubMed PubMed Citation Articles by Lawrence, J. M. Articles by Lund, R. D.

Transplantation of Schwann Cell Line Clones Secreting GDNF or BDNF into the Retinas of Dystrophic Royal College of Surgeons Rats

¹From the Department of Pathology, Institute of Ophthalmology, London, United Kingdom; the ²Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom; the ³Department of Psychology, University of Sheffield, Sheffield, United Kingdom; and the ⁴Moran Eye Center, University of Utah, Salt Lake City, Utah.

PURPOSE. To assess the capacity of a retrovirus-engineered Schwann cell line (SCTM41), transfected with either a glial cell line–derived neurotrophic factor (GDNF) construct or a brain-derived neurotrophic factor (BDNF) construct, to sustain visual function in the dystrophic Royal College of Surgeons (RCS) rat.

METHODS. Cell suspensions were injected into the subretinal space of the right eye of 3-week-old dystrophic RCS rats through a transscleral approach. The left eye remained as an unoperated control. Sham-surgery animals received injections of carrier medium plus DNase to the right eye. All animals were placed on oral cyclosporine. At 8, 12, 16, and 20 weeks of age, animals were placed in a head-tracking apparatus and screened for their ability to track square-wave gratings at various spatial frequencies (0.125, 0.25, and 0.5 cyc/deg). At the end of the experiment, the animals were perfused and processed for histologic assessment of photoreceptor survival.

RESULTS. Animals with SCTM41-GDNF–secreting cells, on average, head tracked longer than animals with SCTM41-BDNF–secreting cells, and both performed better than those injected with the parent SCTM41 line. All tracked longer than sham-surgery or nonsurgical dystrophic eyes. Each cell type demonstrated preservation of photoreceptors up to at least 4 months of age, over and above the sham-surgery control.

CONCLUSIONS. Engineered Schwann cells sustain retinal structure and function in the dystrophic RCS rat. Cells overexpressing GDNF or BDNF had a greater effect on photoreceptor survival than the parent line or sham surgery. This study demonstrates that ex vivo gene therapy and subsequent cell transplantation can be effective in preserving photoreceptors from the cell death that normally accompanies retinal degeneration.

This article has been cited by other articles:

				J. M. Lawrence, S. Singhal, B. Bhatia, D. J. Keegan, T. A. Reh, P. J. Luthert, P. T. Khaw, and G. A. Limb MIO-M1 Cells and Similar Muller Glial Cell Lines Derived from Adult Human Retina Exhibit Neural Stem Cell Characteristics Stem Cells, August 1, 2007; 25(8): 2033 - 2043. [Abstract] [Full Text] [PDF]

				R. B. Wilson, K. Kunchithapautham, and B. Rohrer Paradoxical Role of BDNF: BDNF+/- Retinas Are Protected against Light Damage-Mediated Stress Invest. Ophthalmol. Vis. Sci., June 1, 2007; 48(6): 2877 - 2886. [Abstract] [Full Text] [PDF]

				T. J. McGill, R. D. Lund, R. M. Douglas, S. Wang, B. Lu, B. D. Silver, M. R. Secretan, J. N. Arthur, and G. T. Prusky Syngeneic Schwann Cell Transplantation Preserves Vision in RCS Rat without Immunosuppression Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1906 - 1912. [Abstract] [Full Text] [PDF]

				D. M. Hallman, E. Boerwinkle, V. H. Gonzalez, B. E. K. Klein, R. Klein, and C. L. Hanis A Genome-Wide Linkage Scan for Diabetic Retinopathy Susceptibility Genes in Mexican Americans With Type 2 Diabetes From Starr County, Texas Diabetes, April 1, 2007; 56(4): 1167 - 1173. [Abstract] [Full Text] [PDF]

				R. D. Lund, S. Wang, B. Lu, S. Girman, T. Holmes, Y. Sauve, D. J. Messina, I. R. Harris, A. J. Kihm, A. M. Harmon, et al. Cells Isolated from Umbilical Cord Tissue Rescue Photoreceptors and Visual Functions in a Rodent Model of Retinal Disease Stem Cells, March 1, 2007; 25(3): 602 - 611. [Abstract] [Full Text] [PDF]

				K. Canola, B. Angenieux, M. Tekaya, A. Quiambao, M. I. Naash, F. L. Munier, D. F. Schorderet, and Y. Arsenijevic Retinal Stem Cells Transplanted into Models of Late Stages of Retinitis Pigmentosa Preferentially Adopt a Glial or a Retinal Ganglion Cell Fate Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 446 - 454. [Abstract] [Full Text] [PDF]

				M. Pu, L. Xu, and H. Zhang Visual response properties of retinal ganglion cells in the royal college of surgeons dystrophic rat. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3579 - 3585. [Abstract] [Full Text] [PDF]

				Y. Yoshioka, T. Abe, R. Wakusawa, T. Moriya, S. Mochizuki, Y. Saigo, T. Saito, H. Murata, Y. Tokita, T. Iseya, et al. Recombinant AAV-Transduced Iris Pigment Epithelial Cell Transplantation May Transfer Vector to Native RPE but Suppress Systemic Dissemination Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 745 - 752. [Abstract] [Full Text] [PDF]

				S. Wang, B. Lu, P. Wood, and R. D. Lund Grafting of ARPE-19 and Schwann Cells to the Subretinal Space in RCS Rats Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2552 - 2560. [Abstract] [Full Text] [PDF]

				M. Hojo, T. Abe, E. Sugano, Y. Yoshioka, Y. Saigo, H. Tomita, R. Wakusawa, and M. Tamai Photoreceptor Protection by Iris Pigment Epithelial Transplantation Transduced with AAV-Mediated Brain-Derived Neurotrophic Factor Gene Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3721 - 3726. [Abstract] [Full Text] [PDF]