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Biomedical subjects

S J Ryan

Publications and source records attributed to S J Ryan.

At least 163 records · Page 9Linked to original sources
PubMed1985

Intraocular cannula for continuous, chronic drug delivery. Histopathologic observations and function.

An indwelling cannula for drug delivery was implanted in rabbit eyes. Rabbits were followed up for as long as 1 1/2 years after surgery. They showed almost no adverse effects as a result of the implantation, and cannula patency was demonstrated by the injection of fluorescein sodium through the cannula at various times following surgery. Histopathologic studies using light and electron microscopy were performed at various times to determine the effect of cannula implantation on the eye. Cellular proliferation along the cannula after 1 1/2 years was limited to the region immediately adjacent to the wound and rarely extended to the surrounding retina or ciliary body. The proliferative tissue at the wound site originated mainly from the episclera; the retina and the choroid at the posterior fundus remained intact. Photoreceptor cell metabolism was studied by light microscopic autoradiography following intraocular injection of tritiated leucine to assess photoreceptor outer-segment renewal. Autoradiography showed normal receptor uptake of leucine. A broad band of radioactive labeling of the outer segments resulted from continuous, chronic drug delivery, while a narrow band of labeling resulted from a single intravitreous injection. These data indicate that the cannula system continuously delivered tritiated leucine into the vitreous cavity. We believe that the implanted intraocular cannula, which allows continuous drug delivery on a relatively long-term basis, will be a valuable technique for research and possibly clinical studies.

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PubMed1985

Experimental vitrectomy. A lens-sparing technique in the rabbit eye.

We describe a technique for experimental vitrectomy in the rabbit eye, in which the lens remains intact and the postoperative intraocular inflammatory response is minimized. In comparison with combined vitrectomy and lensectomy, our technique allows the fundus to remain visible for follow-up from the very first postoperative day; traction retinal detachment does not develop as a late complication. We also describe a simple method for gross identification and estimation of the amount of residual vitreous gel on the retinal surface.

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PubMed1985

Experimental vitreous syneresis.

Perfluoropropane gas was injected into the vitreous body of a primate eye. Clinical and morphologic studies revealed that the gas bubble created a large cavity within the vitreous. The cavity that subsequently filled with viscous liquid was completely enveloped by vitreous gel, thus simulating the clinical condition known as vitreous syneresis. The shell of residual vitreous, which was much thicker inferiorly and behind the lens than superiorly, seemed to be an intact and continuous layer. In spite of the extensive syneresis, posterior vitreous detachment failed to develop. Our findings suggest that a vitreous cavity, voluminous as it may be, is not sufficient to cause posterior vitreous detachment in the primate eye.

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PubMed1985

Intraocular cannula for chronic drug delivery. Method and clinical observation.

An intraocular cannula system for chronic drug delivery was designed and tested in rabbits. The cannula was inserted through the pars plana and the tip positioned in the vitreous cavity (distal tip) in a site close to the retinal area of interest. The cannula was stabilized by a silicone plate that was sutured to the sclera. The proximal end of the cannula was attached to a larger diameter silicone tubing which served as a connector to the reservoir for chronic drug delivery. Rabbit eyes with implanted cannulas were followed clinically and electrophysiologically for up to one and a half years. They showed almost no adverse effects as a result of the implantation and cannula patency was demonstrated by the injection of sodium fluorescein through the cannula at various times following surgery. We believe that the implanted intraocular cannula, which allows chronic drug delivery, will be a valuable asset for research and possibly clinical studies.

Animals↗
PubMed1985

Fibronectin of the chorioretinal interface in the monkey: immunohistochemical and immunoelectron microscopic studies.

The distribution of fibronectin in the chorioretinal interface of the monkey eye was studied by indirect immunofluorescent and immunoelectron microscopic techniques. Immunofluorescent staining revealed fibronectin in Bruch's membrane and the choriocapillaris. Immunoelectron microscopic techniques revealed fibronectin associated with basement membranes, collagen fibers and elastic fibers in Bruch's membrane; the stromal side of the basement membrane of the choriocapillaris also showed staining. This study thus demonstrates that fibronectin is an integral component of Bruch's membrane in the monkey eye.

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PubMed1985

Vitreous stimulates proliferation of fibroblasts and retinal pigment epithelial cells.

In proliferative vitreoretinopathy, retinal pigment epithelial cells and glial cells migrate into the vitreous, proliferate, and assume characteristics of myofibroblasts. The addition of vitreous to the culture media stimulates the proliferation of porcine retinal pigment epithelial cells, bovine and lapine dermal fibroblasts but not the proliferation of bovine aortic endothelial cells and smooth muscle cells. The mitogenic activity is not species-specific, since vitreous from various species stimulates the proliferation of these cells. The mitogenic activity is destroyed by heating at 100 degrees C for 10 min or by trypsin treatment. Since the vitreous, under our assay conditions, was not mitogenic for endothelial cells or smooth muscle cells, the mitogenic activity is probably not derived from leakage into the vitreous of circulating fibroblast, epidermal or platelet-derived growth factor.

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PubMed1985

Effect of adriamycin on experimental proliferative vitreoretinopathy in the rabbit.

The cell injection model of proliferative vitreoretinopathy (PVR) in the rabbit was used to study the therapeutic value of intravitreal adriamycin (doxorubicin). Adriamycin in a dose of 10 nmol per eye, if injected at the same time as the cells, controls PVR. At the cell doses used, PVR is not affected if there is a time interval between cell and drug injection. Because of retinal toxicity, as evidenced by electroretinographic and histopathologic changes, the beneficial effects of adriamycin on membrane formation cannot be exploited at this time.

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PubMed1985

An indwelling cannula system for the primate eye.

An indwelling cannula system was designed as an instrument for chronic drug infusion into the vitreous cavity and tested in the cynomolgus monkey eye with repeated injections or continuous infusion using a pumping device. The cannula was passed through the pars plana and its tip situated in the vitreous cavity close to the macular area. Clinical observations up to 18 months did not reveal any adverse effects due to implantation. Histopathological observations from 1 week to 18 months after surgery revealed tissue proliferation around the cannula was minimal and localized only at the wound site, where proliferative tissue originated from the episclera and ciliary epithelium. Retina and choroid at the posterior pole showed normal morphology. Light microscopic autoradiograms demonstrated the function of this system. Injections of tritiated leucine through the cannula resulted in narrow bands of radioactive labelling of the photoreceptor outer segments corresponding to each injection. In contrast, chronic delivery using the pumping device resulted in a diffuse and wide band of labelling. These results strongly suggest that this system did not adversely affect the eye and that repeated intravitreal injections or chronic drug delivery into the vitreous are feasible using this system. Furthermore, autoradiographic results suggest that the drugs infused into the vitreous cavity spread readily into the retina.

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PubMed1985

Consequences of ornithine decarboxylase inactivation by alpha-difluoromethylornithine and 5-fluorouracil on the growth of rabbit fibroblasts.

The role of ornithine decarboxylase and polyamines in proliferative vitreoretinopathy (PVR) is ill-defined. An increase in the activity of this enzyme concurrent with an increase in polyamine levels may be essential in the process of intraocular cellular proliferation. Therefore, in this study, cultured rabbit fibroblasts were exposed to DL-alpha-difluoromethylornithine (alpha-DFMO), a mechanism-based irreversible inactivator of ornithine decarboxylase, alone and in combination with 5-fluorouracil (5-FU). Concentrations of 0.1mM alpha-DFMO and 0.125mM 5-FU decreased rabbit fibroblast cell number by 60% and 65%, respectively, after three days, while with either 5.0mM alpha-DFMO or 0.25mM 5-FU, cell number is decreased by 95%. The effectiveness of inhibitory concentrations of 5-FU and alpha-DFMO together in reducing cell number is additive.

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PubMed1985

Daunomycin in the treatment of experimental proliferative vitreoretinopathy. Effective doses in vitro and in vivo.

In previous studies the authors have shown that daunomycin, an anthracycline antibiotic, when injected into the vitreous effectively controls experimental proliferative vitreoretinopathy. Here we show that by administering daunomycin intravitreally it is possible to achieve in vivo concentrations that prevent fibroblast proliferation in vitro. The authors have also determined that the half-life of daunomycin in the vitreous is 131 min, indicating that a critical concentration is maintained in the eye for longer than 4 hr after a single injection. Using 3H-daunomycin, the authors have found that the drug is eliminated across the retina; no significant binding of the drug to vitreous components occurs. These studies demonstrate that it is possible to define the kinetics of drugs injected into the vitreous; and a knowledge of the distribution of any drug in ocular tissues is necessary to effectively determine whether such drug is of therapeutic value.

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PubMed1984

Surgical removal of vitreous. Its effect on intraocular fibroblast proliferation in the rabbit.

The effect of surgical removal of vitreous on intraocular fibroblast proliferation was studied in an animal model. Forty-eight young adult pigmented rabbits were vitrectomized; four groups of eight animals subsequently received intravitreal injection of tissue-cultured rabbit dermal fibroblasts in doses of 50,000, 100,000, 250,000, and 750,000 cells. As controls, eight vitrectomized rabbits received intravitreal culture medium alone, and the remaining eight vitrectomized rabbits were left uninjected. An additional 40 normal rabbits received the same injections of the same four doses and served as nonvitrectomized controls. All animals were observed for 28 days after injection. The results were dose related and showed that vitrectomy aggravated intraocular fibroblast proliferation in that traction retinal detachment occurred earlier and was more severe in the vitrectomized than in the nonvitrectomized controls.

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PubMed1984

Intravitreal expanding gas bubble. A morphologic study in the rabbit eye.

The morphologic changes induced by an expanding bubble of perfluoropropane (C3F8) gas in the vitreous body have been studied in the rabbit eye by dissecting microscopy and scanning and transmission electron microscopy. Initial expansion of the gas displaces water from the vitreous; the remaining vitreous forms a compressed layer on the retinal surface. Subsequent absorption and contraction of the gas bubble is associated with gradual detachment of the compressed vitreous from the retina. Eventually, vitreous detachment is complete, except for residual attachments posteriorly to the medullary rays and anteriorly to the ciliary processes. The plane of vitreous separation is predominantly at the anatomic vitreoretinal junction, although scattered islands of outer cortical vitreous are found on the surface of the retina.

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PubMed1984

Daunomycin in the treatment of experimental proliferative vitreoretinopathy: retinal toxicity of intravitreal daunomycin in the rabbit.

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.

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PubMed1984

Unexpected traction retinal detachment: a complication of an animal model of pars plana vitrectomy.

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.

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PubMed1984

Proliferative vitreoretinopathy: the rabbit cell injection model for screening of antiproliferative drugs.

Injection into the rabbit vitreous of cultured cells results in a condition that mimics some of the features of proliferative vitreoretinopathy (PVR) in man. Because of its simplicity and reproducibility, this model is especially useful for screening drugs that may control or inhibit intraocular cell proliferation. The cell injection model of PVR is reviewed, and some modifications are described.

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PubMed1984

Experimental model of proliferative vitreoretinopathy (PVR) in the vitrectomised eye: effect of silicone oil.

Silicone oil alone or as an adjunct to vitrectomy is widely used for the treatment of retinal detachment complicated by proliferative vitreoretinopathy (PVR). It appears to reduce the tendency for recurrent traction detachment, but the mechanism of this action is obscure. We have studied the effects of silicone oil in an experimental animal model. Twenty five thousand homologous fibroblasts were injected into the aphakic vitrectomised rabbit eye, and traction detachment of the vascularised retina (medullary rays) regularly resulted. Intraocular silicone oil did not influence the development of this experimental detachment.

Animals↗
PubMed1984

Morphologic evaluation of vitreous collagen after penetrating ocular injury.

Condensation and contraction of the vitreous have been implicated in the development of vitreoretinal traction and traction retinal detachment after penetrating ocular injury. In this study, using the inorganic dye ruthenium-red, we studied ultrastructural changes in vitreous in the rabbit eye after standard penetrating injury and intravitreal blood injection. In normal rabbit vitreous the collagen fibrils have a regular arrangement. In contrast, after a penetrating injury the collagen fibrils appear focally condensed. While it appears unlikely that such a network could alone produce tractional or directional forces, these alterations along the collagen fibrils could provide a scaffold along which contractile cells migrate into the vitreous.

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