Survival of allogeneic porcine retinal pigment epithelial sheets after subretinal transplantation.

PURPOSE To examine morphology after transplantation of organized primary porcine RPE sheets into the porcine subretinal space. METHODS Primary RPE sheets were harvested from freshly enucleated female porcine eyes and embedded in a thin slice of 50% gelatin and 300 mM sucrose before subretinal transplantation into male pigs by using vitrectomy techniques. Thirty-eight animals that underwent surgery were observed for up to 3 months without immune suppression. RESULTS Four days after surgery, the subretinal space contained a multilayer of heavily pigmented RPE that was predominantly Barr body positive. One month after transplantation, there was marked shortening of the outer segments with an intact external limiting membrane. The transplant bed contained a pigmented monolayer in some regions, whereas in other regions the graft was folded into multilayers with degenerated inner layers of transplanted cells despite synthesis of basement membrane. The choroidal vessels and choriocapillaris remained patent in the transplant bed. Barr body positive cells were still present 3 months after surgery. There was no infiltration of the graft site with inflammatory cells. CONCLUSIONS Allogeneic RPE grafts survive in the subretinal space up to 3 months after surgery, and the choriocapillaris remains patent in the transplant bed, although there are many heavily pigmented cells within the transplant bed that are Barr body negative by 3 months. Further work is needed to produce uniform repopulation of a sizable portion of Bruch's membrane with a monolayer of transplanted RPE.

[1]  E. Chihara,et al.  Synthesis of glycosaminoglycans by chick retinal pigment epithelium in vitro , 2005, Graefe's Archive for Clinical and Experimental Ophthalmology.

[2]  P. Wiedemann,et al.  Iris pigment epithelium transplantation , 1997, Graefe's Archive for Clinical and Experimental Ophthalmology.

[3]  P. Gouras,et al.  Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization , 1994, Graefe's Archive for Clinical and Experimental Ophthalmology.

[4]  R. Machemer,et al.  Retinal separation, retinotomy, and macular relocation II. A surgical approach for age-related macular degeneration? , 1993, Graefe's Archive for Clinical and Experimental Ophthalmology.

[5]  R. Machemer,et al.  Retinal separation, retinotomy, and macular relocation I. Experimental studies in the rabbit eye , 1993, Graefe's Archive for Clinical and Experimental Ophthalmology.

[6]  H. Kaplan,et al.  Triple immune suppression increases short-term survival of porcine fetal retinal pigment epithelium xenografts. , 2003, Investigative ophthalmology & visual science.

[7]  Kathleen A. Hansen,et al.  Adeno-associated virus encoding green fluorescent protein as a label for retinal pigment epithelium. , 2003, Investigative ophthalmology & visual science.

[8]  H. Kaplan,et al.  Identification of transplanted retinal pigment epithelium with a novel chromosomal marker , 2003, Current eye research.

[9]  A. Bird,et al.  Retinal pigment epithelium translocation after choroidal neovascular membrane removal in age-related macular degeneration. , 2002, Ophthalmology.

[10]  S. Kochanek,et al.  Long-term transgene expression in the RPE after gene transfer with a high-capacity adenoviral vector. , 2002, Investigative ophthalmology & visual science.

[11]  R. Hilgers,et al.  Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization resulting from age-related macular degeneration: a pilot study. , 2002, American journal of ophthalmology.

[12]  C. Andressen,et al.  Subretinally Transplanted Embryonic Stem Cells Rescue Photoreceptor Cells from Degeneration in the RCS Rats , 2001, Cell transplantation.

[13]  W. Green,et al.  Retinal pigment epithelial cell transplantation after subfoveal membranectomy in age-related macular degeneration: clinicopathologic correlation. , 2001, American journal of ophthalmology.

[14]  C. Hamel,et al.  Retinal dystrophies caused by mutations inRPE65: assessment of visual functions , 2001, The British journal of ophthalmology.

[15]  E. W. Harris,et al.  Leber's Congenital Amaurosis and RPE65 , 2001, International ophthalmology clinics.

[16]  P Esser,et al.  Transplantation of autologous iris pigment epithelium after removal of choroidal neovascular membranes. , 2000, Archives of ophthalmology.

[17]  P. Gouras,et al.  Local immunosuppression prolongs survival of RPE xenografts labeled by retroviral gene transfer. , 2000, Investigative ophthalmology & visual science.

[18]  H. Tomita,et al.  Auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration: short-term results. , 2000, The Tohoku journal of experimental medicine.

[19]  S. Seregard,et al.  Cyclosporine treatment of RPE allografts in the rabbit subretinal space. , 2000, Acta ophthalmologica Scandinavica.

[20]  J. T. Ernest,et al.  Cellular response in rabbit eyes after human fetal RPE cell transplantation , 1999, Graefe's Archive for Clinical and Experimental Ophthalmology.

[21]  H. Kaplan,et al.  Fate of human retinal pigment epithelial cells seeded onto layers of human Bruch's membrane. , 1999, Investigative ophthalmology & visual science.

[22]  M. Humayun,et al.  Allogenic fetal retinal pigment epithelial cell transplant in a patient with geographic atrophy. , 1999, Retina.

[23]  R. Lund,et al.  Visual Field Loss in RCS Rats and the Effect of RPE Cell Transplantation , 1998, Experimental Neurology.

[24]  D. Bok,et al.  Transplantation of retinal pigment epithelial cells and immune response in the subretinal space. , 1998, Investigative ophthalmology & visual science.

[25]  H. Weier,et al.  Optimization of non-isotopic in situ hybridization: detection of the Y chromosome in paraformaldehyde-fixed, wax-embedded cat retina. , 1998, Experimental eye research.

[26]  M. Zarbin,et al.  In vitro transplantation of fetal human retinal pigment epithelial cells onto human cadaver Bruch's membrane. , 1998, Experimental eye research.

[27]  J. Crabb,et al.  Mutation of the gene encoding cellular retinaldehyde–binding protein in autosomal recessive retinitis pigmentosa , 1997, Nature Genetics.

[28]  H. Kaplan,et al.  Harvest and storage of adult human retinal pigment epithelial sheets. , 1997, Current eye research.

[29]  M. Zarbin,et al.  Decreased choriocapillaris perfusion following surgical excision of choroidal neovascular membranes in age-related macular degeneration , 1997, The British journal of ophthalmology.

[30]  M. Zarbin,et al.  Clinicopathologic correlation of localized retinal pigment epithelium debridement. , 1997, Investigative ophthalmology & visual science.

[31]  H. Kaplan,et al.  Retinal Pigment Epithelial Transplantation in the Management of Subfoveal Choroidal Neovascularization , 1997 .

[32]  H. Kaplan,et al.  Retinal pigment epithelial debridement as a model for the pathogenesis and treatment of macular degeneration. , 1996, American journal of ophthalmology.

[33]  H. Kaplan,et al.  Postoperative abnormalities of the choriocapillaris in exudative age-related macular degeneration. , 1996, The British journal of ophthalmology.

[34]  Richard P. Haugland,et al.  Handbook of fluorescent probes and research chemicals , 1996 .

[35]  H. Kaplan,et al.  Débridement of the pig retinal pigment epithelium in vivo , 1995 .

[36]  M. Silverman,et al.  Retinal pigment epithelial repopulation in monkeys after submacular surgery. , 1995, Archives of ophthalmology.

[37]  H. Kaplan,et al.  Choriocapillaris atrophy after submacular surgery in presumed ocular histoplasmosis syndrome. , 1995, Archives of ophthalmology.

[38]  P. Gouras,et al.  Patch transplants of human fetal retinal pigment epithelium in rabbit and monkey retina. , 1995, Investigative ophthalmology & visual science.

[39]  J. Streilein,et al.  Immunologic consequences of intraocular implantation of retinal pigment epithelial allografts. , 1994, Experimental eye research.

[40]  P. Gouras,et al.  Retinal pigment epithelial transplants and retinal function in RCS rats. , 1993, Investigative ophthalmology & visual science.

[41]  M. Uyama,et al.  [Changes in the intermediate stage of retinal degeneration after intravitreal injection of ornithine]. , 1993, Nippon Ganka Gakkai zasshi.

[42]  D. Anderson,et al.  Recovery of photoreceptor outer segment length and analysis of membrane assembly rates in regenerating primate photoreceptor outer segments. , 1993, Investigative Ophthalmology and Visual Science.

[43]  G. Peyman,et al.  A technique for retinal pigment epithelium transplantation for age-related macular degeneration secondary to extensive subfoveal scarring. , 1991, Ophthalmic surgery.

[44]  B. Pfeffer,et al.  Chapter 10 Improved methodology for cell culture of human and monkey retinal pigment epithelium , 1991 .

[45]  H. Sheedlo,et al.  Photoreceptor Cell Rescue at Early and Late RPE-Cell Transplantation Periods During Retinal Disease in RCS Dystrophic Rats , 1991, Journal of neural transplantation & plasticity.

[46]  D. Anderson,et al.  Retinal reattachment of the primate macula. Photoreceptor recovery after short-term detachment. , 1989, Investigative ophthalmology & visual science.

[47]  M. Boulton,et al.  Transplantation of retinal pigment epithelium using a pars plana approach , 1989, Eye.

[48]  Linxi Li,et al.  Transplantation of retinal pigment epithelial cells to immature and adult rat hosts: short- and long-term survival characteristics. , 1988, Experimental eye research.

[49]  C. Toris,et al.  Functional recovery of retinal pigment epithelial damage in experimental retinal detachment. , 1987, Investigative ophthalmology & visual science.

[50]  P. Gouras,et al.  Transplantation of cultured rabbit retinal epithelium to rabbit retina using a closed-eye method. , 1987, Investigative ophthalmology & visual science.

[51]  J. Aubin,et al.  Localization of laminin, type IV collagen, fibronectin, and heparan sulfate proteoglycan in chick retinal pigment epithelium basement membrane during embryonic development. , 1985, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[52]  P. Gouras,et al.  Transplantation of cultured human retinal epithelium to Bruch's membrane of the owl monkey's eye. , 1985, Current eye research.

[53]  V. Reppucci,et al.  RPE destruction causes choriocapillary atrophy. , 1984, Investigative ophthalmology & visual science.

[54]  P. Henkind,et al.  The relationship between retinal pigment epithelium and the choriocapillaris. , 1983, Transactions of the ophthalmological societies of the United Kingdom.

[55]  R. E. Kalina,et al.  Clinical-ultrastructural study of thioridazine retinopathy. , 1982, Ophthalmology.

[56]  M. Kaiser-Kupfer,et al.  Experimental model of gyrate atrophy in animals. , 1981, Ophthalmology.

[57]  J. G. Garner,et al.  Staining sex chromatin; Biebrich scarlet and fast green FCF as a mixture versus their use in sequence. , 1966, Stain technology.