| 1. |
- Ghosh, Fredrik, et al.
(författare)
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Selective Removal of Photoreceptor Cells In Vivo Using the Biodegradable Elastomer Poly(Glycerol Sebacate)
- 2009
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Ingår i: Tissue Engineering. Part A. - 1937-335X. ; 17:13-14, s. 1675-1682
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Tidskriftsartikel (refereegranskat)abstract
- Retinal transplantation experiments have advanced considerably during recent years, but remaining diseased photoreceptor cells in the host retina physically obstruct the development of graft-host neuronal contacts which are required for vision. We here report selective removal of photoreceptors using the biodegradable elastomer poly(glycerol sebacate) (PGS). A 1x3 mm PGS membrane was implanted in the subretinal space of normal rabbit eyes, and morphologic specimens were examined with hematoxylin and eosin staining and a panel of immunohistochemical markers. Seven days postoperatively, a patent separation of the neuroretina and retinal pigment epithelium was found as well as loss of several rows of photoreceptors in combination with massive TUNEL staining for apoptosis in the outer nuclear layer. After 28 days, the neuroretina was reattached, the PGS membrane had degraded, and photoreceptors were absent in the implantation area. Activated Müller cells were found in the entire retina in 7-day specimens, and in the implantation area after 28 days. AII amacrine and rod bipolar cell morphology was not affected, except for disrupted dendritic branching which was present in rod bipolar cells in 28-day specimens. We conclude that retinal detachment induced by the biodegradable PGS membrane creates a permissive environment in which graft-host neuronal connections may be facilitated in future retinal transplantation experiments.
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| 2. |
- Pritchard, Christopher D., et al.
(författare)
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The use of surface modified poly(glycerol-co-sebacic acid) in retinal transplantation
- 2010
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 31:8, s. 2153-2162
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Tidskriftsartikel (refereegranskat)abstract
- Retinal transplantation experiments have advanced considerably during recent years, but remaining diseased photoreceptor cells in the host retina and inner retinal cells in the transplant physically obstruct the development of graft-host neuronal contacts which are required for vision. Recently, we developed methods for the isolation of donor photoreceptor layers in vitro, and the selective removal of host photoreceptors in vivo using biodegradable elastomeric membranes composed of poly(glycerol-co-sebacic acid) (PGS). Here, we report the surface modification of PGS membranes to promote the attachment of photoreceptor layers, allowing the resulting composite to be handled surgically as a single entity. PGS membranes were chemically modified with peptides containing an arginine-glycine-aspartic acid (RGD) extracellular matrix ligand sequence. PGS membranes were also coated with electrospun nanofiber meshes, containing laminin and poly(epsilon-caprolactone) (PCL). Following in vitro co-culture of biomaterial membranes with isolated embryonic retinal tissue, composites were tested for surgical handling and examined with hematoxylin and eosin staining and immunohistochemical markers. Electrospun nanofibers composed of laminin and PCL promoted sufficient cell adhesion for simultaneous transplantation of isolated photoreceptor layers and PGS membranes. Composites developed large populations of recoverin and rhodopsin labeled photoreceptors. Furthermore, ganglion cells, rod bipolar cells and All amacrine cells were absent in co-cultured retinas as observed by neurofilament, PKC and parvalbumin labeling respectively. These results facilitate retinal transplantation experiments in which a composite graft composed of a biodegradable membrane adhered to an immature retina dominated by photoreceptor cells may be delivered in a single surgery, with the possibility of improving graft-host neuronal connections. (C) 2009 Elsevier Ltd. All rights reserved.
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