Schwann Cell Therapy Sustains Long–Term Visual Function in the Royal College of Surgeons Rat

Abstract

Abstract: : Purpose:To determine how effective Schwann cell grafts are in sustaining vision over time in the Royal College of Surgeons (RCS) rat. Methods:Human Schwann cells (hSc) were delivered into the sub–retinal space of 10 dystrophic RCS rats at 23 days of age: 5 further rats received sub–retinal media injections as sham controls. Both groups received treatments in the right eye followed by immunosupression with cyclosporine. Rats were followed serially using the OptoMotor head tracking apparatus to determine visual acuity until 7 months of age, electroretinograms and tectal thresholding were then performed and finally the eyes were processed for anatomical examination. Results:The visual acuity early after application of Schwann cells was 0.427 c/d with congenic RCS giving 0.6 c/d and dystrophic RCS 0.35 c/d: shams were not significantly different from dystrophics. By 4 months of age the hSc treated animals tracked at 0.41 c/d with the best at 0.564 c/d: shams were 0.3 c/d and dystrophics 0.22 c/d. At 7 months of age the hSc group performed at 0.265 c/d with the best animal at 0.453 c/d: dystrophic and sham animals dropped below 0.1 c/d (considered blind) at around 150 days for dystrophics and after 175 days for shams. Flicker ERG responses were obtained in hSc injected eyes at 7 months of age (2 out of 4), reaching in the best case, 5.6 µV at 3Hz and fusing at 15 Hz, while untreated and sham injected eyes were already unresponsive by 6 months of age. Tectal threshold responses recorded at 7 months also gave good results showing values of 1.3 log units over background in the best hSc animal. These tests indicate sustained high order functional vision. Anatomical studies at 7 months, showed photoreceptor rescue in the same animal with both rods and cones still present. Conclusions:Schwann cell therapy has shown significant long–term improvement in visual function with photoreceptor rescue up to at least six months after application. Sham treatments showed a minor short–lived improvement over dystrophic RCS.

Keywords: retinal degenerations: cell biology • transplantation • photoreceptors: visual performance