A novel platform for minimally invasive delivery of cellular therapy as a thin layer across the subretina for treatment of retinal degeneration

Ygal Rotenstreich; Adi Tzameret; Sapir E. Kalish; Michael Belkin; Amilia Meir; Avraham J. Treves; Arnon Nagler; Ifat Sher

doi:10.1117/12.2078972

20 March 2015 A novel platform for minimally invasive delivery of cellular therapy as a thin layer across the subretina for treatment of retinal degeneration

Ygal Rotenstreich, Adi Tzameret, Sapir E. Kalish, Michael Belkin, Amilia Meir, Avraham J. Treves, Arnon Nagler, Ifat Sher

Author Affiliations +

Proceedings Volume 9307, Ophthalmic Technologies XXV; 93071X (2015) https://doi.org/10.1117/12.2078972
Event: SPIE BiOS, 2015, San Francisco, California, United States

Abstract

Incurable retinal degenerations affect millions worldwide. Stem cell transplantation rescued visual functions in animal models of retinal degeneration. In those studies cells were transplanted in subretinal "blebs", limited number of cells could be injected and photoreceptor rescue was restricted to areas in proximity to the injection sites. We developed a minimally-invasive surgical platform for drug and cell delivery in a thin layer across the subretina and extravascular spaces of the choroid. The novel system is comprised of a syringe with a blunt-tipped needle and an adjustable separator. Human bone marrow mesenchymal stem cells (hBM-MSCs) were transplanted in eyes of RCS rats and NZW rabbits through a longitudinal triangular scleral incision. No immunosuppressants were used. Retinal function was determined by electroretinogram analysis and retinal structure was determined by histological analysis and OCT. Transplanted cells were identified as a thin layer across the subretina and extravascular spaces of the choroid. In RCS rats, cell transplantation delayed photoreceptor degeneration across the entire retina and significantly enhanced retinal functions. No retinal detachment or choroidal hemorrhages were observed in rabbits following transplantation. This novel platform opens a new avenue for drug and cell delivery, placing the transplanted cells in close proximity to the damaged RPE and retina as a thin layer, across the subretina and thereby slowing down cell death and photoreceptor degeneration, without retinal detachment or choroidal hemorrhage. This new transplantation system may increase the therapeutic effect of other cell-based therapies and therapeutic agents. This study is expected to directly lead to phase I/II clinical trials for autologous hBM-MSCs transplantation in retinal degeneration patients.

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Ygal Rotenstreich, Adi Tzameret, Sapir E. Kalish, Michael Belkin, Amilia Meir, Avraham J. Treves, Arnon Nagler, and Ifat Sher "A novel platform for minimally invasive delivery of cellular therapy as a thin layer across the subretina for treatment of retinal degeneration", Proc. SPIE 9307, Ophthalmic Technologies XXV, 93071X (20 March 2015); https://doi.org/10.1117/12.2078972

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