Subretinal Neovascularization

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Raja Narayanan - One of the best experts on this subject based on the ideXlab platform.

Stephen J. Ryan - One of the best experts on this subject based on the ideXlab platform.

  • Cellular response in Subretinal Neovascularization induced by bFGF-impregnated microspheres.
    Investigative ophthalmology & visual science, 1999
    Co-Authors: Hideya Kimura, Taiji Sakamoto, Chris Spee, David R. Hinton, Yuichiro Ogura, Yasuhiko Tabata, Yoshito Ikada, Stephen J. Ryan
    Abstract:

    PURPOSE. To determine the sequence of cellular changes associated with a new rabbit model of Subretinal Neovascularization (SRN) induced by Subretinal injection of basic fibroblast growth factor (bFGF)-impregnated microspheres. METHODS. bFGF-impregnated gelatin microspheres, prepared by forming a polyion complex between gelatin and bFGF, were Subretinally implanted into rabbit eyes. The eyes were studied by immunochemistry at 3 days to 8 weeks after implantation. Antibodies to CD4, CD8, cytokeratin, CD31, glial fibrillary acidic protein (GFAP), and RAM11 were used. RESULTS. Cytokeratin-positive retinal pigment epithelial (RPE) cells appeared on day 3 and continued to increase in number in the Subretinal space throughout the growth of the SRN membrane, becoming the predominant cell type. Macrophages (RAM11-positive) appeared early, but most disappeared within 7 days. GFAP-positive Muller cells were evident early in the retina but migrated into the Subretinal space after 7 days; the gliotic adhesion they formed between the retina and the SRN membrane was prominent at 8 weeks. CD31-positive endothelial cells were first evident at 14 days and formed neovascular channels that were still present for up to 8 weeks. CD4-and CD8-positive lymphocytes appeared in the early stages but were few in number. CONCLUSIONS. SRN membranes are primarily composed of RPE cells and vascular endothelial cells. The membrane adheres to the retina by a gliotic band. The cellular components involved in the membrane of this model resemble those found in SRN membranes removed from patients with age-related macular degeneration.

  • Effect of Intravitreal Administration of Indomethacin on Experimental Subretinal Neovascularization in the Subhuman Primate
    Archives of Ophthalmology, 1995
    Co-Authors: Taiji Sakamoto, Danilo Soriano, João Nassaralla, Todd L. Murphy, Arutun Oganesian, Chris Spee, David R. Hinton, Stephen J. Ryan
    Abstract:

    Objective: To examine the effect of indomethacin, a cyclooxygenase (CO) inhibitor, on laser-induced Subretinal Neovascularization (SRN) in the monkey. The CO pathway of arachidonic acid metabolism plays an important role in angiogenesis, and the inhibition of CO is known to inhibit angiogenesis in the cornea and in certain tumors. Materials and Methods: A cannula was implanted into the vitreous cavity of 11 eyes of six monkeys and connected to an osmotic minipump. Indomethacin (25 μg/d) was delivered into the vitreous through the cannula for 14 days (seven eyes). Vehicle alone was injected for 14 days as a control (four eyes). Argon laser photocoagulation was then performed (eight spots at the posterior pole in each eye) to induce SRN. Fundus photographs and fluorescein angiograms were taken periodically to document the evolution of SRN. Light and electron microscopic examination was performed on two eyes of each group 8 weeks after photocoagulation. Results: Subretinal Neovascularization developed from 2 to 4 weeks after photocoagulation. The incidence of SRN, indicated by fluorescein leakage, was significantly lower (P Conclusions: Intravitreal administration of indomethacin inhibits the formation of laser-induced SRN in monkey eyes. This is consistent with the participation of the CO pathway in the process of SRN formation and suggests that this pathway could be a potential target in the treatment of SRN.

  • Pericytes of Newly Formed Vessels in Experimental Subretinal Neovascularization
    Archives of ophthalmology (Chicago Ill. : 1960), 1995
    Co-Authors: Tatsuro Ishibashi, Taiji Sakamoto, Hajime Inomata, Stephen J. Ryan
    Abstract:

    Objective: To examine the role of pericytes in the progression of Subretinal Neovascularization in a primate model. Methods: Subretinal Neovascularization was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 3, 7, 14, and 21 days after photocoagulation and were studied with light and electron microscopy. Results: Three days after photocoagulation, newly formed vessels were observed in the choroid and Subretinal space. Although most of these vessels had an immature appearance and consisted only of endothelial cells that formed narrow lumens, mitotic figures of pericytes were occasionally found near the endothelial cells. Seven days after photocoagulation, all of the newly formed vessels possessed pericytes. Fourteen days after photocoagulation, many vessels appeared to be mature. Many sites of pericyte-endothelial cell contact were observed. These contacts were composed of cytoplasmic interdigitation and membrane apposition. By 21 days after photocoagulation, the mature vessels had increased in number, and the endothelial cells had many fenestrations with diaphragms. The pericyte coverage of the endothelial cells was less at this stage than at 14 days after photocoagulation, and sites of pericyte-endothelial cell contacts were observed only rarely. Conclusion: Pericytes are involved in maturation of the endothelial cells that form Subretinal new vessels.

  • A new model of Subretinal Neovascularization in the rabbit.
    Investigative ophthalmology & visual science, 1995
    Co-Authors: Hideya Kimura, Taiji Sakamoto, Chris Spee, David R. Hinton, Yuichiro Ogura, Yasuhiko Tabata, Yoshito Ikada, Stephen J. Ryan
    Abstract:

    Purpose. To establish a new model of Subretinal Neovascularization (SRN) in the rabbit by implanting basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres beneath the retina. Methods. Basic fibroblast growth factor-impregnated gelatin microspheres were prepared by forming a polyion complex between gelatin and bFGF. The microspheres, containing 2.5 μg of bFGF, were injected into the Subretinal space of rabbit eyes (n = 29). Control eyes (n = 10) received bFGF-free gelatin microspheres. Eyes were followed up for 3 days to 8 weeks by ophthalmoscopy, photography, fluorescein angiography, light microscopy, and transmission electron microscopy. Results. Twenty of 24 experimental eyes (83%) showed fluorescein leakage from SRN 2 weeks after implantation of the bFGF-impregnated microspheres. This leakage continued for 2 to 6 more weeks. In striking contrast, control eyes showed no fluorescein leakage. Histologic examination revealed SRN in all the experimental eyes but in none of the control eyes. Conclusions. Subretinal implantation of bFGF-impregnated gelatin microspheres induces reproducible SRN in the rabbit. Invest Ophthalmol Vis Sci. 1995 ;36 :2110-2119.

  • Subretinal Neovascularization in the rat induced by IRBP synthetic peptides.
    Experimental eye research, 1994
    Co-Authors: Taiji Sakamoto, Tatsuro Ishibashi, Hajime Inomata, Hiroki Sanui, Toshihiko Kohno, Ken Ichi Takahira, Leon Kohen, Stephen J. Ryan
    Abstract:

    The present study was undertaken to develop a new animal model of Subretinal Neovascularization that does not involve traumatic manipulation of the eye. Using this model, the mechanism of Subretinal Neovascularization and its penetration through Bruch's membrane, and the various factors that contribute to this process were then examined. Male Lewis rats were immunized with interphotoreceptor retinoid binding protein (IRBP) peptide R-4, and the eyes histologically examined at various times up to 45 days after immunization. On day 12 after immunization, inflammatory cells were identified primarily in the anterior segment of the eye, with scattered cells in the retina and choroid. The inflammation was most prominent on day 14, by which time many eyes showed serous retinal detachment. By day 18 the inflammation had declined in intensity, but branches of the retinal vessels were seen extending into the choroid. Examination on day 30 revealed even fewer inflammatory cells but an accumulation of retinal pigment epithelial cells and mononuclear cells was present in the Subretinal space. Examination on day 45 revealed no appreciable inflammation, but typical new vessels were found in the eyes from five of the 13 rats (38%) examined at that point. Mild inflammation of the retinochoroidal tissue can induce Subretinal new vessels in rats, and this model will be useful for further study of Subretinal new vessel formation.

Jay Chhablani - One of the best experts on this subject based on the ideXlab platform.

Kopal Mithal - One of the best experts on this subject based on the ideXlab platform.

Harsha Rao - One of the best experts on this subject based on the ideXlab platform.

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