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Elliott Sohn, Kristan Sorenson Worthington, Chunhua Jiao, Emily E. Kaalberg, Stephen R Russell, Katherine N. Gibson-Corley, Robert F Mullins, Edwin M Stone, Budd Tucker; Compatibility of a biodegradable retinal cell graft for the treatment of retinal degenerative blindness. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4585.
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© ARVO (1962-2015); The Authors (2016-present)
Photoreceptor cell replacement has demonstrated potential for restoring vision in retinal degenerations, but only a small fraction of transplanted cells survive and integrate into the host retina. Polymeric support scaffolds have been shown to enhance the efficacy of cell survival and integration post-transplantation. The purpose of this study was to test retinal biocompatibility of a hydrogel-based biodegradable polymer scaffold, poly (caprolactone) (PCL).
Methacrylate-functionalized PCL scaffolds were polymerized with Irgacure 651 using two-photon polymerization. Four month old Yucatan mini pigs had vitrectomy and hyaloid induction. A subretinal bleb was raised with BSS, followed by placement of PCL scaffold in the subretinal space, then fluid-air exchange. Contralateral pig eyes underwent control surgery. Animals were sacrificed 1 month (n=5 eyes) or 3 months (n=5 eyes) after surgery at which time ophthalmoscopy and spectral-domain OCT (SD-OCT) were performed. Pathological analyses were performed on paraffin sections of control and treated eyes. Immunostaining with CD45, CD34, CD31 antibodies was done on sections from polymer transplantation sites.
All 10 treated eyes had complete, spontaneous retinal reattachment with implants identifiable in the subretinal space on ophthalmoscopy and SD-OCT. On SD-OCT the surface of the polymer was hyper-reflective while the body was hypo-reflective compared to the retina. No eyes had evidence of intraocular inflammation. Hematoxylin-eosin stained sections through a subset of injected eyes demonstrated subretinal location of the implanted polymer. Retinal integrity, including intact photoreceptor outer segments, was relatively well maintained. No aberrant CD45, CD34, CD31 positive cells were detected in the subretinal space around the polymer transplantation sites.
PCL polymers, which support maintenance of human iPSC-derived retinal cells, can be successfully delivered to the subretinal space and are well-tolerated by the host retina. These scaffolds may be ideal for retinal transplantation.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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