Integration of Feline Neural Precursor Cells After Subretinal Transplantation Into Abyssinian Cats Affected With Hereditary Retinal Degeneration

Abstract

Purpose:: The purpose was to determine whether neural progenitor cells survive subretinal transplantation, show evidence of integration, and exert positive effects on the feline host degenerative retina.

Methods:: 45-day old feline fetal brains were obtained, neural precursors cultured and labeled by EGFP through transfection with the lentiviral vector FUGW. The recipients were six 2-5 year-old Abyssinian cats affected with hereditary rod cone degeneration. Aseptic vitreo-retinal surgery was performed as previously described, and 75 microliters of pre-labeled donor cells (750,000) were injected subretinally into one eye. The fellow eye was not treated. Post-op. examination included ophthalmoscopy, bilateral full-field electroretinography (ERG) and immunohistochemistry for Vimentin and GFAP. Histological sections were evaluated using fluorescence and confocal microscopy. Five cats were euthanized at 2 (n=2) and 4 weeks (n=3) post-op. and one was used for long-term follow-up.

Results:: No adverse effects were noted. ERGs showed up to 20% reduced ERG b-wave amplitudes 4 weeks post-op., but long-term amplitudes increased in the transplanted eye 10 months post-op. compared to the untreated eye. Morphology has not yet been evaluated, but in the others showed GFP+ cells with resemblance to RPE, Mueller, and bipolar cells.

Conclusions:: Feline neural progenitor cells survive up to 4 weeks subretinally, migrate in the dystrophic feline retina and develop into cells with features characteristic of the local microenvironment. ERG responses were reduced post-op. but one animal studied long-term shows evidence suggestive of functional benefit.

Keywords: transplantation • retinal degenerations: hereditary • differentiation