Transplantation of Schwann Cell Line Clones Secreting GDNF or BDNF into the Retina of the Royal College of Surgeons Rat Prolongs Visual Function

Abstract

Abstract: : Purpose: To examine whether two engineered Schwann cell line clones derived from a parent Schwann cell line, SCTM41 (CD rat), transfected with a glial-derived neurotrophic factor (GDNF) or a brain-derived neurotrophic factor (BDNF) construct enhance rescue from functional deterioration in RCS rats. Both factors are known to have retinal activity. Methods: Cell suspensions were injected into the subretinal space of one eye of 3-week-old RCS rats using a trans-scleral approach. Sham-operated rats received injections of carrier medium plus DNase. All animals were placed on cyclosporin. At 4, 8 and 12 weeks post-transplantation animals were placed in a head-tracking apparatus and screened for their ability to track square wave gratings of varying spatial frequencies (0.125, 0.25 and 0.5 cycles per degree). At the end of the experiment animals were perfused and processed for histological assessment of photoreceptor survival. Electrophysiological recordings were made from the superior colliculus of some animals. Results: Animals with GDNF-SCTM41 secreting cells on average head-tracked for longer periods than animals with BDNF-SCTM41 secreting cells and both performed better than those with the parent SCTM41 line. All performed better than sham-operated or dystrophic animals. Each cell type demonstrated preservation of photoreceptors up to 4 months of age over and above sham-operated controls. Conclusions: Engineered Schwann cells can preserve retinal structure and function in the RCS rat. Cells over-expressing GDNF demonstrated substantially greater functional rescue than the parent line, emphasising the importance of this growth factor.

Keywords: transplantation • growth factors/growth factor receptors • degenerations/dystrophies