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Ratnesh K Singh, Laurence Occelli, Simon M Petersen-Jones, Francois Binette, Oscar Cuzzani, Igor O Nasonkin; Transplantation of laboratory-grown human retinal tissue in the subretinal space of the cat eye. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2986.
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© ARVO (1962-2015); The Authors (2016-present)
Allogeneic human fetal retinal tissue has been used in the past in a few clinical studies to restore vision in patients with severe retinal degenerative diseases. In vitro generated human retinal tissue has been shown to have both a molecular signature and development dynamics that are very similar to human fetal retina. In this study, we investigate the survival of human pluripotent stem cell derived retinal tissue in the subretinal space of a large animal model (cat). Such laboratory grown human retina could represent an alternative to human fetal allograft that would be more commercially feasible and ethically acceptable.
Human embryonic stem cell (HESC) derived retinal tissue was introduced into the subretinal space of wild-type cats following a pars plana vitrectomy (n=3 eyes). Oral prednisone at an anti-inflammatory dose was given for the duration of the study. The eyes were examined by fundoscopy and spectral domain optical coherence tomography (OCT) imaging for adverse effects due to the presence of the subretinal grafts. Five weeks following grafting the cats were euthanized and immunohistochemistry of retinal sections performed using human specific antibodies (HNu, Ku80) and a microglia/macrophage marker (IBA-1).
We successfully delivered hESC derived retinal tissue into the subretinal space of the cat eye. There was no gross host retinal inflammation detectable on fundus examination and OCT imaging. OCT showed the presence of grafts in the subretinal space (Fig 1). Immunostaining of retinal cryo-sections with HNu and Ku80 antibodies revealed the presence of the grafts of human tissue in the cat subretinal space (Fig 1). The majority of cells in the graft had cytoplasmic staining instead of nuclear staining. Immunostaining with IBA-1 showed a significant presence of activated microglia within the graft, indicative of host rejection.
We show that hESC derived retinal tissue can be successfully transplanted into the cat subretinal space without inducing a severe host inflammatory response. Nevertheless, as expected with such large xenograph transplantation and its associated surgical trauma, there was evidence of a rejection process. Further refinement of the transplantation technique coupled with improved immunosuppression strategy is required for stable grafting of tissue patches into the subretinal space.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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