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  • 1
    Electronic Resource
    Electronic Resource
    Retrovirus-mediated gene transfer targeted to retinal photocoagulation sites (1998)
    Springer
    Diabetologia 41 (1998), S. 500-506 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Gene therapy ; diabetic retinopathy ; photocoagulation ; retrovirus ; β-galactosidase.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic retinopathy is a major cause of acquired blindness due to the development of retinal neovascularization and associated traction retinal detachment. It is commonly treated with retinal photocoagulation therapy; however, progression to blindness remains a significant problem. To determine the feasibility of adjunctive anti-angiogenic gene therapy, we evaluated the capability of retroviral vectors, which transfer exogenous genes only into dividing cells, to transfer and express a β-galactosidase gene selectively into photocoagulation sites. Thirty-five rabbits received 30 retinal photocoagulation burns in the right eye followed 2 days later by β-galactosidase (G1nBgSvNa) or control (G1XSvNa) vector injection into the subretinal space. β-galactosidase expression was observed in the photocoagulation sites from 5 days after vector administration (31.7 ± 7.0 %) to 12 weeks (6.7 ± 3.4 %). Immunohistochemical studies of the treated retinas using antibody Ber-MAC3 and anti-cytokeratin antibodies revealed that transduced cells were macrophages and retinal pigment epithelial cells. To determine feasibility in a primate, two monkeys received 10 laser burns in the macula superior to the fovea followed 2 days later by G1nBgSvNa vector. β-galactosidase expression was found in photocoagulation sites and foveal retina was well preserved. We conclude that gene transfer to retinal photocoagulation sites provides stable expression of the transduced gene with relatively high efficiency. This feasibility study suggests the possibility of transferring genes encoding for anti-angiogenic factors into photocoagulation sites to improve the efficacy of laser photocoagulation therapy. [Diabetologia (1998) 41: 500–506]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050938
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of the vitreous on retinal wound-healing (1986)
    Springer
    Graefe's archive for clinical and experimental ophthalmology 224 (1986), S. 576-579 
    Details
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The healing process of experimental retinal wounds in nonvitrectomized and vitrectomized rabbit eyes was compared. Using light, transmission and scanning electron microscopy, a significant difference was observed at the late stages of the healing process. The retinal wounds in the nonvitrectomized eyes healed properly, forming regular and smooth scars, while the scars that developed in the vitrectomized eyes were irregular and hypertrophic. Our observations suggest that the vitreous plays a role in normal healing of retinal wounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02154747
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  • 3
    Electronic Resource
    Electronic Resource
    Reply (1997)
    Springer
    Graefe's archive for clinical and experimental ophthalmology 235 (1997), S. 190-191 
    Details
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00941729
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  • 4
    Electronic Resource
    Electronic Resource
    Posterior vitreous separation and retinal detachment induced by macrophages (1987)
    Springer
    Graefe's archive for clinical and experimental ophthalmology 225 (1987), S. 279-284 
    Details
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Macrophages, which migrate into the vitreous in conditions such as vitreous hemorrhage and penetrating ocular injury, may contribute to the development of intravitreous cellular proliferation and posterior vitreous separation. To investigate this possibility, activated macrophages were harvested from the peritoneal cavity and injected into the vitreous of rabbits. As early as 8 days after macrophage injection, posterior vitreous separation and glial epiretinal membrane formation began to occur. Two weeks after injection, vitreous strands that approached the optic disc and medullary rays were evident; fibroblasts proliferated over the disc or rays and induced retinal detachment. These findings support the hypothesis that macrophages in the vitreous may, in part, mediate cellular proliferation and posterior vitreous separation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02150149
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  • 5
    Electronic Resource
    Electronic Resource
    Control of experimental massive periretinal proliferation by daunomycin: dose-response relation (1983)
    Springer
    Graefe's archive for clinical and experimental ophthalmology 220 (1983), S. 233-235 
    Details
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A condition similar to massive periretinal proliferation in man can be produced in rabbits by injecting homologous fibroblasts into the vitreous. We have studied the effect of daunomycin, a cytotoxic drug, in this model to determine a dose which would not be toxic to the retina but would be effective in preventing proliferation of the injected fibroblasts and eventual retinal detachment. The results of this study demonstrate that daunomycin at a dose of 9 nmol per eye reduces the incidence of retinal detachment by over 50%. Doses higher than 30 nmol per eye are toxic to the retina.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02308080
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  • 6
    Electronic Resource
    Electronic Resource
    Unexpected traction retinal detachment: a complication of an animal model of pars plana vitrectomy (1984)
    Springer
    Graefe's archive for clinical and experimental ophthalmology 221 (1984), S. 182-185 
    Details
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated a rabbit model of the vitrectomized eye. In 16% of eyes the surgical procedure leads to the development of traction detachment of the vascularized portion of the retina (medullary ray). The traction originates in the vitreous base and is probably transmitted to the posterior retina via a sheet of detached vitreous cortex. In time course and morphology this differs from the experimental traction detachment seen after the injection of cells. Provided this complication is recognized, the vitrectomized rabbit eye is a useful and economic model for experimental studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02134262
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  • 7
    Electronic Resource
    Electronic Resource
    Daunomycin in the treatment of experimental proliferative vitreoretinopathy: retinal toxicity of intravitreal daunomycin in the rabbit (1984)
    Springer
    Graefe's archive for clinical and experimental ophthalmology 221 (1984), S. 210-213 
    Details
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The retinal toxicity of daunomycin, a drug that effectively suppresses experimental proliferative vitreoretinopathy (PVR), was studied in the rabbit by clinical examination, electroretinography (ERG), light microscopy, and electron microscopy. Although no toxicity was observed at the therapeutically effective dose of 10 nmol per eye, the safety margin is too small to recommend this drug for therapy of proliferative vitreoretinopathy in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02134142
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  • 8
    Electronic Resource
    Electronic Resource
    Transplantation of cultured human retinal pigment epithelium into rabbit subretina (1993)
    Springer
    Graefe's archive for clinical and experimental ophthalmology 231 (1993), S. 737-742 
    Details
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transplantation of normal retinal pigment epithelium (RPE) into a diseased eye holds promise for treatment of several blinding disorders. Previuos studies have involved immunosuppression and implantation of freshly isolated cells. We report here the successful transplantation of cultured human RPE cells into rabbits that were not immunosuppressed. A modified pars plana transvitreal technique was used for RPE transplantation. The cultured RPE cells, loaded with carbon as a marker, were transplanted into the denuded Bruch's membrane of albino rabbits. The animals were followed for from 1 week to 3 months. On histologic examination at 2 months, no infiltrating lymphocytes were found in the vitreous cavity or choroid, even though Bruch's membrane was damaged. At about 3 months there were some macrophages in the subretina of transplanted eyes, indicating that an immunoreaction does occur eventually. Electron microscopy of the transplanted RPE showed apical-basal polarity and gap junctions. Restored function was attested to by the presence of phagosomes and phagocytosed outer segments in the transplanted cells. Our findings suggest that there is a weak, delayed immunoreaction to human RPE cells transplanted beneath the retina of the rabbit; however, functional recovery of the transplanted cells occurs before this immune response develops.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00919290
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  • 9
    Electronic Resource
    Electronic Resource
    Ability of retroviral transduction to modify the angiogenic characteristics of RPE cells (1998)
    Springer
    Graefe's archive for clinical and experimental ophthalmology 236 (1998), S. 220-229 
    Details
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract • Background: Retinal pigment epithelial (RPE) cells play an important role in the modulation of ocular angiogenesis. Transduction of RPE cells with retroviral vectors bearing modulating genes can result in long-term transgene expression and may alter the angiogenic characteristics of RPE cells. This study was designed to determine whether changes in angiogenic characteristics of RPE cells result from transduction with retroviral vectors bearing modulating genes, using in vitro angiogenic assays, including analysis of endothelial proliferation and wound healing. • Methods: Human RPE cells were transduced with retroviral vectors bearing either a urokinase-type plasminogen activator (u-PA) or a tissue-type plasminogen activator (t-PA) cDNA. Ten weeks after gene transfer, RPE cells transduced with the u-PA (u-PA-RPE cells) or the t-PA cDNA (t-PA-RPE cells), or untransduced (control) RPE cells, were cocultured with human umbilical vein endothelial cells (HUVECs) by contacting and non-contacting coculture methods. The effects of these cells on proliferation and in vitro “wound healing” of HUVECs were evaluated. • Results: Over 18 weeks, u-PA-RPE cells released large amounts of biologically active u-PA (total amount, 50.2 ± 9.7 ng/106 cells/24 h), while t-PA-RPE cells released large amounts of functional t-PA (15.4 ± 3.2 ng/106 cells/24 h). Control RPE cells did not release any detectable t-PA or u-PA. In the proliferation assay, u-PA-RPE cells stimulated HUVEC proliferation in contacting cell cultures, but not in non-contacting cell cultures. In contrast, t-PA-RPE cells, normal RPE cells or exogenous u-PA had no effect on HUVEC proliferation. In the wound healing assay, u-PA-RPE cells in contacting coculture and exogenous u-PA stimulated wound healing of HUVECs, while non-contacting u-PA-RPE cells, t-PA-RPE cells and normal RPE cells had no effect on HUVEC wound healing. RPE cells transduced with u-PA secreted large amounts of u-PA for as long as 18 weeks, and these cells stimulate HUVEC proliferation and in vitro wound healing. As a result, the angiogenic characteristics of RPE cells can undergo long-term changes. • Conclusions: These results suggest that genetically modified RPE cells can be used to modulate ocular angiogenesis and may have potential for gene therapy of ocular diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004170050068
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  • 10
    Electronic Resource
    Electronic Resource
    Natural history of choroidal neovascularization induced by vascular endothelial growth factor in the primate (2000)
    Springer
    Graefe's archive for clinical and experimental ophthalmology 238 (2000), S. 326-333 
    Details
    ISSN: 1435-702X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Background: A new model of choroidal neovascularization (CNV) has been developed in the primate by implanting vascular endothelial growth factor (VEGF)-impregnated microspheres in the subretinal space. Methods: CNV was induced in Macaca mulatta monkeys by implanting VEGF-impregnated gelatin microspheres in the subretinal space. Progression of CNV was followed for 24 weeks after surgery using fluorescein angiography. Eyes were enucleated at various time points, and lesions were evaluated for evidence of CNV by light microscopy and by immunohistochemical staining. Results: CNV developed in 12 (92%) of 13 eyes. Fluorescein leakage was first observed in the 2nd postoperative week and was apparent for the following 12 weeks. CD31 staining for endothelial cells was first observed at day 7 and was evident for the following 8 weeks. Glial fibrillary acidic protein staining revealed a glial adhesion between the proliferative membrane and the retina at 6 weeks after implantation. Smooth muscle actin-positive cells were found a + 2 weeks and remained prominent for at least the next 6 weeks. Cytokeratin-positive retinal pigment epithelial (RPE) cells, first identified in the proliferative membrane at day 3, predominated throughout the growth of the membrane. Macrophages (RAM-II positive) were present at day 3 but were no longer observed after day 7. Conclusion: In monkeys, subretinal implantation of VEGF-impregnated gelatin microspheres leads to the development of CNV. Early, disciform and reparative stages of CNV were observed, similar to those seen in humans. This model will be useful for studying the pathogenesis of CNV and for evaluating potential treatment strategies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004170050360
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