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(Investigative Ophthalmology and Visual Science. 2008;49:416-421.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-0992
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Morphological and Functional Rescue in RCS Rats after RPE Cell Line Transplantation at a Later Stage of Degeneration

Shaomei Wang,1,2 Bin Lu,1,2 Sergej Girman,1,2 Toby Holmes,2,3 Nicolas Bischoff,2 and Raymond D. Lund1,2

1From the Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon; the 3Catherine McCauley Centre, University College Dublin, Dublin, Ireland; and 2Moran Eye Center, University of Utah, Salt Lake City, Utah.

PURPOSE. It is well documented that grafting of cells in the subretinal space of Royal College of Surgeons (RCS) rats limits deterioration of vision and loss of photoreceptors if performed early in postnatal life. What is unclear is whether cells introduced later, when photoreceptor degeneration is already advanced, can still be effective. This possibility was examined in the present study, using the human retinal pigment epithelial cell line, ARPE-19.

METHODS. Dystrophic RCS rats (postnatal day [P] 60) received subretinal injection of ARPE-19 cells (2 x 105/3 µL/eye). Spatial frequency was measured by recording optomotor responses at P100 and P150, and luminance threshold responses were recorded from the superior colliculus at P150. Retinas were stained with cresyl violet, retinal cell–specific markers, and a human nuclear marker. Control animals were injected with medium alone. Animals comparably treated with grafts at P21 were available for comparison. All animals were treated with immunosuppression.

RESULTS. Later grafts preserved both spatial frequency and threshold responses over the control and delayed photoreceptor degeneration. There were two to three layers of rescued photoreceptors even at P150, compared with a scattered single layer in sham and untreated control retinas. Retinal cell marker staining showed an orderly array of the inner retinal lamination. The morphology of the second-order neurons was better preserved around the grafted area than in regions distant from graft. Sham injection had little effect in rescuing the photoreceptors.

CONCLUSIONS. RPE cell line transplants delivered later in the course of degeneration can preserve not only the photoreceptors and inner retinal lamination but also visual function in RCS rats. However, early intervention can achieve better rescue.




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S. Wang, S. Girman, B. Lu, N. Bischoff, T. Holmes, R. Shearer, L. S. Wright, C. N. Svendsen, D. M. Gamm, and R. D. Lund
Long-term Vision Rescue by Human Neural Progenitors in a Rat Model of Photoreceptor Degeneration
Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 3201 - 3206.
[Abstract] [Full Text] [PDF]


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