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Biomedical subjects

T E Ogden

Publications and source records attributed to T E Ogden.

At least 19 recordsLinked to original sources
PubMed1997

Anterior segment prosthesis development: retinal function following anterior segment removal.

Replacement of the entire anterior segment of the eye is a very ambitious and complex endeavor and it is not known whether the retina remains functional when the anterior structures have been removed. We used routine histo-pathologic evaluation and electroretinographic measurements to determine the structural and functional status of rabbit retinas following surgical removal of the internal anterior structures (iris, ciliary body, and lens) and replacement of the vitreous with silicone oil. In some cases, we were able to record both a scotopic and a photopic electroretinographic response as long as 15 weeks after complete removal of the internal anterior segment structures. Although many hurdles remain and more efficacious surgical techniques and biomaterials need to be developed, our results suggest that, in the rabbit, the retina may continue to function in the absence of critical anterior segment structures.

Animals↗
PubMed1994

Transforming growth factor-beta regulates human retinal pigment epithelial cell phagocytosis by influencing a protein kinase C-dependent pathway.

BACKGROUND: Transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of many ocular diseases, including proliferative vitreoretinopathy. We examined the effect of TGF-beta on the phagocytosis of rod outer segments by retinal pigment epithelium (RPE), which is a major function of RPE, and investigated the dependence of this effect on the protein kinase C (PKC) pathway. METHODS: Phagocytotic uptake of fluoresceinated bovine rod outer segments was determined by flow cytometry. RPE cells were treated with TGF-beta 1 or TGF-beta 2 and their effects on phagocytosis were examined. The effects of various PKC inhibitors (calphostin C, staurosporine, and extended exposure to phorbol 12-myristate 13-acetate, PMA) and a stimulator (brief exposure to PMA) on RPE phagocytosis was evaluated. RESULTS: Both TGF-beta 1 and TGF-beta 2 up-regulated RPE phagocytosis and PMA abolished the up-regulating effect of TGF-beta. In contrast, PKC inhibition by staurosporine and calphostin C resulted in increased phagocytosis. A combination of TGF-beta and PKC inhibitor treatment did not produced any additive effect on phagocytosis. CONCLUSION: We concluded that TGF-beta up-regulates human RPE phagocytosis, but that this effect is counteracted by PKC activation. It is possible that this TGF-beta-induced effect is due, in part, to a negative modulation of the PKC-dependent pathway.

Alkaloids↗
PubMed1994

Dexamethasone induced proliferation of cultured retinal pigment epithelial cells.

Dexamethasone (DEX) is a glucocorticoid that is widely used after vitreoretinal surgery and may have mitogenic properties. This study was initiated to determine if human cultured retinal pigment epithelium (RPE) cells express glucocorticoid receptor and proliferate in response to DEX stimulation. Glucocorticoid receptor mRNA was detected in RPE cells by means of reverse transcriptase polymerase chain reaction. To determine the effect of DEX on RPE cell proliferation in vitro, we cultured human RPE cells with various concentrations for DEX for 5 days and determined the effects on cell number and incorporation of tritiated thymidine. DEX treatment with a DEX dose of 1 microgram/ml in the presence or absence of serum resulted in a maximal 2-3 times increase in cell number. Autoradiography after thymidine incorporation revealed a greater than 2-fold increase in incorporating cells at this same dose. These results indicate that DEX causes cultured human RPE cells to proliferate and suggest that it may have a growth factor-like action.

Cell Count↗
PubMed1994

Effect of leukopenia on experimental post-traumatic retinal detachment.

Macrophages are invariably present in the intraocular membranes of patients with traumatic proliferative vitreoretinopathy (PVR). There are two sources from which these macrophages could be recruited: adjacent tissues and the systemic circulation. In the study described herein, the role of circulating white blood cells and monocytes in experimental, traumatic PVR was studied. The circulating white blood cells of 20 rabbits were depleted by intravenous injection of strontium-89. Posterior perforating eye injury with subsequent intravitreal injection of autologous whole blood or autologous activated macrophages was then performed on these leukopenic animals. The experiments demonstrated that severe bone marrow depression reduced significantly the incidence of retinal detachments in eyes receiving whole blood, and reduced the severity of retinal detachments in eyes injected with activated macrophages. An association between the degree of leukopenia, monocytopenia, and protection from retinal detachment was demonstrated. These results support the hypothesis that macrophage infiltration is an important component of intraocular cellular proliferation, but does not exclude the role of other types of white blood cells in the pathogenesis of PVR.

Animals↗
PubMed1993

Transplantation of cultured human retinal pigment epithelium into rabbit subretina.

Transplantation of normal retinal pigment epithelium (RPE) into a diseased eye holds promise for treatment of several blinding disorders. Previous 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.

Adult↗
PubMed1993

Allotransplantation of rabbit retinal pigment epithelial cells double-labelled with 5-bromodeoxyuridine (BrdU) and natural pigment.

To facilitate identification of transplanted retinal pigment epithelial (RPE) cells, we sought to double-label the cells with 5-bromodeoxyuridine (BrdU) and with natural pigment. The BrdU is not lost during cell division but does require immunohistochemical methods for visualization; the pigment, on the other hand, allows immediate, obvious identification, but is gradually lost with cell division. Together they provide a convenient, long-term double label. Herein we report the successful allotransplantation of double-labelled RPE cells onto Bruch's membrane of albino rabbits. The labelled cells were localized by anti-BrdU antibody and the avidin biotin-alkaline phosphatase complex (ABC-AP) method, and by visible inclusions of pigment. Using this double-label method, allotransplanted RPE cells could be readily and reliably identified on the recipient Bruch's membrane eight months after transplantation. The cells had distinct basal and apical morphology, and were in close contact with the photoreceptor outer segments of the host. This successful allotransplantation raises the possibility that the subretinal space of the rabbit might enjoy some degree of immunologic privilege.

Animals↗
PubMed1992

Retinal pigment epithelium implantation in the rabbit: technique and morphology.

Dysfunction of the retinal pigment epithelium (RPE) is a major component of many degenerative disorders of the retina. We have developed a modified pars plana technique for subretinal implantation of homologous, cultured, carbon-loaded RPE cells in the rabbit. The natural history and morphologic behavior of the implanted RPE cells for up to 6 weeks after transplantation were observed in successful procedures.

Animals↗
PubMed1992

In vitro stimulation of retinal pigment epithelium proliferation by taurine.

Taurine is an amino acid that is essential for retinal integrity and function. Although it has been suggested that the ratio of melatonin to taurine in the interphotoreceptor matrix may regulate the phagocytosis of outer segments by retinal pigment epithelial (RPE) cells, the effect of taurine on the RPE has not been studied. Using cultured RPE cells, we found that in vitro taurine specifically stimulated proliferation of human and rabbit RPE, but had only minimal effect on cultured scleral fibroblasts. The RPE proliferation was due to more cells entering into S-phase and thus an increase in DNA synthesis, was not dependent upon cell density, and was most pronounced in the presence of a low concentration of fetal bovine serum.

Animals↗
PubMed1992

Cultures of human retinal pigment epithelium. Modulation of extracellular matrix.

The extracellular matrix of retinal pigment epithelial (RPE) cells is an important component of the fibroelastic membranes formed in proliferative vitreoretinopathy (PVR). These membranes consist of cells intermingled with fibrillar proteins, such as elastin and collagen. Because RPE cells may be exposed to vitreous and serum-derived factors in conditions that lead to PVR, the effects of vitreous and serum on the deposition of fibrillar proteins by RPE cells were studied using radioactive labeling and indirect immunofluorescence techniques. The RPE cells, modulated by combined vitreous and serum into a fibrocytic-like appearance, deposited less fibroelastic proteins per cell. However, as a result of simultaneous cell proliferation, the total deposition of fibroelastic proteins per culture was increased. Indirect immunofluorescence studies suggest that it is type I collagen that is altered in the matrix of these modulated cell cultures. This information is important in pathologic conditions characterized by intraocular cell proliferation and fibroelastic membrane formation; these phenomena are seen in many vitreoproliferative disorders.

Cell Count↗
PubMed1991

Synthesis of extracellular matrix by macrophage-modulated retinal pigment epithelium.

In proliferative vitreoretinopathy, macrophages and retinal pigment epithelial cells are associated with microfibrillar matrix proteins in the vitreous cavity, but the contribution of this extracellular matrix to the pathophysiology is not known. We used radiolabeling techniques on cultured human retinal pigment epithelial cells to correlate the secretion of extracellular matrix proteins with macrophage-induced modulation of cell proliferation and morphologic features. Retinal pigment epithelial cells incubated in a macrophage-conditioned medium assumed fibrocytelike morphologic characteristics, grew faster, and exhibited a decreased cellular release of fibrillar and nonfibrillar matrix components. However, due to a simultaneous greater increase in cell numbers in these modulated cultures, the total production of fibrillar and nonfibrillar matrix components by the culture population was increased.

Cell Division↗
PubMed1991

Subretinal endophotocoagulation. A new model of subretinal neovascularization in the rabbit.

The disciform response of age-related macular degeneration and other diseases is determined by the development of subretinal neovascularization (SRN). Experimental animal models of SRN based on disruption of Bruch's membrane have been studied extensively during the past decade. Argon laser photocoagulation-induced SRN in primates is one such model, but this is associated with extensive retinal damage. Because the injured retina could be angiogenic, and is not present in clinical SRN, this model might be more relevant if this factor could be eliminated. The current study was conducted with the primary aim of producing a rabbit model of SRN that minimizes retinal damage. Argon laser endophotocoagulation was applied beneath the retina of albino rabbits to achieve this goal. Although argon photocoagulation does not cause clinically apparent SRN (i.e., associated with leaking and pooling of fluorescein) in the rabbit, all laser lesions produced in the current study contained microscopic SRN. A rabbit SRN model would be highly desirable as a step toward other animal models, perhaps involving nonhuman primates, which might ultimately be clinically more relevant.

Animals↗
PubMed1990

Choroidal endothelial junctions in primates.

Junctional ultrastructure of endothelial cells of the choroid was studied with freeze-fracture electron microscopy. A network of multi-stranded linear aggregates was found on arterial endothelial membrane E faces in association with the apposing arterial membrane P face strands. The complexity of the junctional strands decreased as vessel diameter decreased. The choriocapillaris showed staggered junctional strands exclusively on the membrane P face. Junctions of venules and veins were represented by plasmalemmal folds with sparse intramembrane particles on the P face. Freeze-fracture cytochemistry with the membrane probe, filipin, revealed two dissimilar membrane domains: one, an area of membrane fluidity at the junctional strands; and the other, identified by the incorporation of cholesterol into the membrane lipid bilayer, a stable membrane domain. The latter was present throughout endothelial membranes, but was especially prominent on the rims of fenestrations of the choriocapillaris.

Animals↗
PubMed1989

Experimental subretinal neovascularization in the rabbit.

Subretinal neovascularization (SRN) in the rabbit was induced by subretinal injection of vitreous without rupture of Bruch's membrane. Eight of 26 eyes developed SRN. The incidence of SRN rose from 33% to 57% in a period of 4-40 weeks. Because of the absence of any fluorescein angiographic indication of SRN, these occult new vessels were identified by light and transmission electron microscopy. Histological examination showed that these newly formed vessels are composed of continuous capillaries with the morphologic characteristics of choriocapillaris, including diaphragmed fenestrations, basement membranes, and junctional complexes. The new vessels originated from the choriocapillaris and penetrated through Bruch's membrane into the subretinal space, where they were associated with the degenerated sensory retina and proliferating glial and/or RPE cells. This experiment provides a model of SRN without breaks in Bruch's membrane.

Animals↗
PubMed1989

Functional role of spines in the retinal horizontal cell network.

Compartmental models derived from serial electron-microscopic reconstructions of horizontal cell processes entering cone pedicles and rod spherules are used to show that these processes have the morphological and electrical characteristics of dendritic spines. Properties of these spines are incorporated into a distributed model of the horizontal cell network. Expressions relating the magnitude of conductance changes applied at the spine heads to hyperpolarization of cells within the network are derived. Model analyses show that spine properties play a critical role in determining network responses. Specifically, increasing spine stem resistance increases the network input resistance and space constant, hyperpolarizes the resting potential, decreases response to full-field light stimuli, and increases response to small light spots. Increasing spine-stem resistance also decouples potential at the spine head from potential at the cell body. This result suggests that the location of feedback neurotransmitter release sites (e.g., at the spine heads versus the cell body) may have a profound influence on properties of horizontal cell inhibition of cone response. Because of these important functional consequences, structurally realistic models of the horizontal cell network must incorporate spine properties.

Animals↗
PubMed1989

Morphologic observations of retinal pigment epithelial proliferation and neovascularization in the rabbit.

Neovascularization and proliferation of the retinal pigment epithelium (RPE) was induced in the rabbit by subretinal injection of vitreous without rupture of Bruch's membrane. New vessels developed between the layer of RPE and photoreceptor outer segments, but were enveloped in proliferating RPE. For this reason they were occult; no fluorescein leakage was visible by angiography. The vessels were identified only by histologic examinations. Endothelial cell budding was the initial stage of vessel development, first seen two weeks after injection. The new vessels grew from the choriocapillaris, penetrated Bruch's membrane, and spread into the subretinal space, despite the absence of subretinal fluid. Fenestrations with diaphragms were found in the endothelial walls during the earliest stages of vessel formation, and were also present in the fully matured vessels. Intermediate junctional complexes were frequently observed among the endothelial cells. During maturation of these plexi, junctions changed from open to putative tight junctions. The mature vessels were ultimately completely enveloped by collagen and RPE cells. Our results show that all new vessels in this animal model have the morphologic characteristics of choriocapillaris. We assume that they leak fluorescein, as does the choriocapillaris, but that the dye has no opportunity to pool in the subretinal space and thus cannot be seen during angiography.

Animals↗
PubMed1989

The internal horizontal cell of the frog: spatial summation.

The receptive field properties of internal horizontal cells (IHCs) were studied in the frog Rana pipiens. The space constant of each cell was determined by the use of stimulus spots of various sizes or by moving a light slit across the retina, varied from 100-500 microns by the former and 100-720 microns by the latter method. A similar range of values has been reported for Xenopus although its IHCs are much larger than the IHCs of Rana. Apparently, coupling among the IHCs is more efficient in the latter than in the former retina. The large range in values suggests substantial variation in coupling efficiency among cells of the same retina.

Animals↗
PubMed1988

Cellular proliferation induced by subretinal injection of vitreous in the rabbit.

A new experimental model of subretinal cellular proliferation, based on injection of autologous vitreous into the subretinal space of rabbits, was studied by light and electron microscopy. As early as five days after injection, proliferation of retinal pigment epithelial (RPE) and retinal glial cells was observed in the subretinal space. These morphologically distinct proliferating cells were sometimes joined by junctional complexes. Morphologically, the proliferating RPE cells resembled either RPE cells or fibroblasts. Some proliferating RPE cells also retained their epithelial characteristics (ie, basement membranes and cell junctions), while others were partially dedifferentiated and showed some embryonic features. New formation of melanin could be identified within the proliferated RPE cells, which could account, in part, for the hyperpigmentation at the site of the bleb caused by the injection of vitreous. The results demonstrated that injection of autologous vitreous into the subretinal space can lead to subretinal proliferation of retinal glial and RPE cells in the rabbit.

Animals↗