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S J Ryan

Publications and source records attributed to S J Ryan.

At least 55 records · Page 3Linked to original sources
PubMed1997

MHC class II positive retinal pigment epithelial (RPE) cells can function as antigen-presenting cells for microbial superantigen.

Retinal pigment epithelial (RPE) cells induced to express MHC class II (HLA-DR) by incubation with interferon gamma (IFN-gamma) were investigated for their ability to present a microbial superantigen to T lymphocytes. Superantigens bind to MHC class II antigens and appear to play a role in a number of infectious and autoimmune diseases through stimulation of large numbers of T cells. Primary cultures of human RPE cells treated with IFN-gamma for three days to induce HLA-DR expression bound staphylococcal enterotoxin E (SEE) via HLA-DR and presented SEE to T cells as measured by proliferation of purified peripheral blood T cells and IL-2 synthesis by the Jurkat T cell line. Untreated RPE cells were essentially ineffective as superantigen presenting cells. These results suggest that MHC class II expressing RPE cells could contribute to immune and inflammatory activity in the eye by presenting superantigens to T lymphocytes.

Antigen Presentation↗
PubMed1997

cis-Hydroxyproline inhibits proliferation, collagen synthesis, attachment, and migration of cultured bovine retinal pigment epithelial cells.

PURPOSE: Proliferative vitreoretinopathy (PVR) is characterized by the proliferation and migration of retinal pigment epithelial (RPE) and other cells into the vitreous cavity. The PVR membrane formation also is associated with collagen production by RPE. The authors examined the effect of a proline analog, cis-hydroxyproline (CHP), on proliferation, collagen synthesis, attachment, and migration of bovine RPE in vitro. METHODS: The effect of CHP on cell proliferation was determined as a function of dosage and days in culture by counting the cell numbers on days 3, 6, and 9. Collagen synthesis was determined by trichloroacetic acid precipitation of the radiolabeled samples before and after bacterial collagenase digestion. The attachment assay involved type I collagen or fibronectin substrates or both (2.5 micrograms/well). For migration experiments, RPE cells were removed from a defined area of a confluent culture, and migration was quantitated by counting the number of cells migrating into the denuded area over 30 hours. RESULTS: The addition of CHP inhibited RPE proliferation in both a dose- and a time-dependent manner; collagen synthesis, attachment, and migration also were inhibited by CHP in a dose-dependent manner. When the culture plates were coated with collagen, < 100 micrograms/ml of CHP had no effect on cell attachment. Higher doses of CHP resulted in mild inhibition of attachment on collagen-coated plates. Simultaneous addition of L-proline to the cultures resulted in blockade of these inhibitory effects on proliferation, collagen synthesis, attachment, and migration. CONCLUSIONS: The results show that RPE functions critical to the development of PVR are inhibited by CHP, suggesting the possibility that this drug may have potential clinical application.

Animals↗
PubMed1997

Arthrographic effect induced by therapeutic ultrasound in magnetic resonance imaging of the wrist: a preliminary investigation.

OBJECTIVE: To evaluate the potential arthrographic effect of therapeutic ultrasound applied before magnetic resonance imaging (MRI) of the wrist. SUBJECTS AND METHODS: MRI of the wrist was performed in 6 asymptomatic volunteers before and after ultrasound therapy of the carpus. For each patient, ultrasound therapy was performed by a trained physiotherapist for 10 minutes, with doses titrated to the maximum tolerated without pain. The amount of fluid within the wrist joints before and after therapy was assessed subjectively by 2 reviewers, as well as objectively by digital analysis. RESULTS: Subjective appraisal of the images indicated that after ultrasound therapy there was an increase in joint fluid within the distal radioulnar joint in 4 volunteers, the midcarpal joint in 4 and the radiocarpal joint in 2. Computerized digital analysis of joint fluid confirmed an average volumetric increase in wrist joint fluid of 52.8% in 3 of the volunteers. The discomfort of the therapy was graded as 1/10 by 5 of the subjects and 4/10 by a single subject. CONCLUSIONS: Therapeutic ultrasound may be a useful adjuvant tool in the noninvasive induction of joint fluid before MRI of the wrist.

Adult↗
PubMed1996

Retrovirus-mediated suicide gene transduction in the vitreous cavity of the eye: feasibility in prevention of proliferative vitreoretinopathy.

In proliferative vitreoretinopathy (PVR), retinal pigment epithelial cells, fibroblasts, or other proliferating cells form contractile membranes in the vitreous cavity of the eye, resulting in traction retinal detachment. Retroviral vector-mediated transfer is a suitable method to transduce the herpes simplex virus thymidine kinase (HSV-tk) gene into proliferating cells in PVR, allowing for the selective killing of these cells. To determine the potential of gene transduction in the environment of the vitreous cavity, we evaluated the effect of vitreous humor on retroviral vector-mediated gene transduction of rabbit dermal fibroblasts in vitro and studied in vivo transduction in rabbit experimental PVR with retroviral vector G1BgSvNa. In addition, we studied the bystander effect in vitro and in vivo in a rabbit model of PVR, with low percentages of HSV-tk-positive cells. Finally, we evaluated the efficacy of intravitreal administration of HSV-tk retroviral vector G1TkSvNa followed by ganciclovir (GCV) in the prevention of experimental PVR. Vitreous humor reduced gene transfer efficiency in vitro in a dose-dependent manner. LacZ expression was found in cells of preretinal or intravitreal membranes of animals of both in vivo and in vitro transduction groups; however, in vivo transduction resulted in a decreased number of transduced cells, with a relative transduction efficiency of approximately 2%. Transduction of HSV-tk was associated with a powerful bystander effect both in vitro and in vivo with significant effects even when HSV-tk-positive cells represented only 1% of the population. In vivo transduction with G1TkSvNa followed by GCV significantly inhibited the development of PVR (p < 0.05). These results suggest that retroviral vector-mediated transfer of HSV-tk into the proliferating cells in PVR may be feasible and may provide a novel therapeutic strategy for this disease.

Animals↗
PubMed1996

Soluble tumor necrosis factor receptors are present in human vitreous and shed by retinal pigment epithelial cells.

Tumor necrosis factor-alpha (TNF) has been implicated in the pathogenesis of several retinal diseases. Soluble forms of the TNF receptors, p55 (55 kDa) and p75 (75 kDa), have recently been identified in biological fluids and may regulate TNF activity. The potential biological significance of these receptors for the human retina was examined by determining their presence in human vitreous and their release from eye cup explants in which the retina has been removed leaving an intact retinal pigment epithelium (HRPE). Normal human vitreous and conditioned medium from eye-cup HRPE explants demonstrated the presence of soluble p55 and p75. Soluble p55 was significantly more abundant than p75 in all vitreous samples (P < 0.03). Conditioned medium from eye-cup HRPE explants contained significantly more soluble p55 than p75 (P < 0.00002). Enzyme-linked immunosorbent assay showed the presence of soluble p55, and not p75, in conditioned medium from primary cultured HRPE cells. Activation of the protein kinase C pathway in these cells with the phorbol ester PMA significantly increased the release of soluble p55 (P < or = 0.001); whereas, pharmacological inhibition of protein kinase C with calphostin-C significantly decreased the shedding of p55 (P < or = 0.001). The results indicate that primary cultured HRPE cells shed p55 and regulate this shedding in part through the protein kinase C pathway. The presence of soluble TNF receptors within normal human vitreous and within conditioned medium from the eye-cup HRPE explant model suggests that these soluble receptors may have a biological function in the eye.

Aged↗
PubMed1996

Vitreous body affects activation and maturation of monocytes into macrophages.

BACKGROUND: Macrophages play an important role in several ocular diseases. Because macrophages localized in ocular tissues may be derived from blood monocytes, the effect of vitreous [containing transforming growth factor-beta 2 (TGF-beta 2) and hyaluronic acid] on blood monocytes, maturating in the tissue to macrophages, was determined. METHODS: Human monocytes were cultured with and without vitreous in RPMI 1640 medium containing human AB serum. As a parameter of activation the release of interleukin-6 was measured by the B9 bioassay; as an indication of maturation, the content of acid phosphatase and the increase in cell size were assessed. RESULTS: Monocytes in vitreous-containing medium grew more slowly than did control monocytes. Monocytes cultured in 10% vitreous released 51% less, and in 20% vitreous 73% less, interleukin-6 than control monocytes. Vitreous at 20% significantly (P = 0.0075) reduced the amount of acid phosphatase by 80% over a 4-day culture period. This reduction was partially eliminated with neutralizing antibodies to TGF-beta (P = 0.0014). Furthermore, human recombinant TGF-beta 2 increased the activity of acid phosphatase in monocytes at 1.25 ng/ml and reduced it (P < 0.0001) at higher concentrations (5-10 ng/ml). Hyaluronic acid showed an effect additive to that of TGF-beta in further diminishing the amount of acid phosphatase (P = 0.026). CONCLUSION: Vitreous exerts a regulatory effect on monocyte activation and maturation by its content of TGF-beta and possibly hyaluronic acid and may, thus, modify the inflammatory or immune response in the eye.

Acid Phosphatase↗
PubMed1996

Vitamin E succinate inhibits proliferation and migration of retinal pigment epithelial cells in vitro: therapeutic implication for proliferative vitreoretinopathy.

BACKGROUND: Retinal pigment epithelial (RPE) cells play an important role in proliferative vitreoretinopathy (PVR). Vitamin E succinate is an ester form of a potent biological antioxidant, vitamin E, and has unique effects on various cells. We examined the effect of vitamin E succinate on proliferation and migration of cultured bovine RPE cells, since these are critical steps in the development of PVR. METHODS: Bovine RPE cells were cultured in minimal essential medium (MEM) containing 10% fetal calf serum (MEM-10). Cells were incubated with MEM-10 containing 25 microM vitamin E, vitamin E succinate, butylated hydroxytoluene (BHT) or d-mannitol. Cell proliferation was assessed by counting cell numbers on days 2, 4 and 6. 3H-Thymidine uptake was also examined in RPE cells incubated with various forms of vitamin E-- vitamin E, vitamin E succinate, Trolox, gamma-tocopherol, vitamin E acetate, vitamin E phosphate, vitamin E nicotinate--or antioxidants-- BHT or d-mannitol (25 microM each). RPE cell migration was studied as follows: A small area (5 x 15 mm) of confluent cultured RPE cells was denuded using a straight razor blade and incubation was continued for 20 h with MEM-10 containing vitamin E, vitamin E succinate, gamma-tocopherol or BHT. The number of cells that migrated into the denuded area from the wound edge in each microscopic field (x20) was counted and expressed as a percentage of control (MEM-10 alone). RESULTS: The antioxidants, vitamin E and BHT, stimulated RPE cell proliferation and 3H-thymidine incorporation compared with the control, while vitamin E succinate significantly inhibited both proliferation and 3H-thymidine uptake (IC50, 23 microM). Other forms of vitamin E or d-mannitol had no effect. Neither vitamin E nor BHT had a significant effect on RPE cell migration (108.2% and 112.6% of control, respectively), but vitamin E succinate inhibited migration (58.3%). Cell viability, assessed by the trypan blue dye exclusion test, was not impaired by a 3-day incubation with 50 microM of vitamin E succinate. CONCLUSIONS: An ester form of a physiological antioxidant, vitamin E succinate, inhibits RPE cell proliferation and migration without causing cellular toxicity. These findings suggest its therapeutic potential for the pharmacological treatment of PVR.

Animals↗
PubMed1996

Retinal pigment epithelial cell proliferation: potentiation by monocytes and serum.

BACKGROUND: The development of proliferative vitreoretinopathy (PVR) results often from a breakdown of the blood-retina barrier and the intraocular accumulation of serum proteins and leukocytes, particularly monocytes, that then come into contact with retinal pigment epithelial (RPE) cells. To examine the effect of these two factors on RPE proliferation, which is characteristic of PVR, we used a coculture system of blood monocytes and human RPE cells. METHODS: RPE cells were incubated with a variable number of monocytes at different serum concentrations and assayed for proliferation by [3H]-thymidine incorporation and cell counting. To assess cell-cell communication. RPE cells were labeled with 2', 7' -bis(carboxyethyl)-5(and 6) carboxyfluorescein acetoxy-methyl ester, and the dye transfer to monocytes was analyzed using an UV microscope. RESULTS: Monocytes (P < 0.0004) and serum (P < 0.0001), each on its own, significantly stimulated RPE cell growth, and these two variables were interrelated (P < 0.0001), showing a potentiating synergism. In serum-free medium, monocytes increased proliferation to just above control levels, whereas the same number of monocytes in 5% serum increased the [3H]-thymidine incorporation 3.8 times. This effect was greatly reduced by prevention of direct cell contact by means of placement of a well insert, which also lessened the monocyte-induced proliferation in both serum-free and serum-containing medium. Furthermore, the transfer of the intracellular dye from RPE cells to cocultured monocytes indicates that RPE cells transferred parts of their cytoplasm to monocytes. CONCLUSION: These observations underline the importance of protein leakage through a damaged blood-ocular barrier and of direct contact of monocytes/macrophages with RPE cells, as well as their reciprocal potentiating effect on RPE cell proliferation. Thus, early stabilization of the blood-ocular barrier, which would preclude or reduce protein leakage and invasion of inflammatory cells into the eye, could be a target for pharmacologic prevention of PVR.

Blood Physiological Phenomena↗
PubMed1996

Anterior proliferative vitreoretinopathy in the silicone study. Silicone Study Report Number 10.

BACKGROUND: As part of the design of the Silicone Study, a new classification of proliferative vitreoretinopathy (PVR) was developed that distinguishes the different types of contraction found in PVR. In contrast to the original Retina Society system that emphasized the post-equatorial retinal pathology (posterior PVR), the Silicone Study classification system included the characteristic types of contraction found in both the equatorial region and the pre-equatorial retina and vitreous base (anterior PVR). METHODS: The authors contrast (1) preoperative and intraoperative findings and (2) vision and anatomic outcomes in the cohort of anterior PVR eyes with the cohort of posterior-only PVR eyes. For the cohort of eyes randomized to perfluoropropane gas (C3F8) or silicone oil, the authors carry out univariate and multivariate analyses to assess the predictive value of baseline and intraoperative parameters on vision and anatomic outcome. RESULTS: Anterior PVR was present in 321 eyes (79%) and was more prevalent in eyes that had undergone an unsuccessful vitrectomy before study entry than in eyes that underwent a primary vitrectomy for PVR (88% versus 73%; P < 0.001). Compared with eyes that had posterior PVR at the preoperative examination, eyes that had anterior PVR tended to (1) be graded (Retina Society classification system) as D-1 or worse (86% versus 49%; P < 0.0001), (2) have worse (< 2/200) visual acuity (93% versus 86%; P = 0.003), (3) have more hypotony (24% versus 11%; P = 0.03), more edema (8% versus 2%; P = 0.04), more aqueous flare (P = 0.02), more macular pucker (69% versus 52%; P = 0.005), and more intravitreal contraction (21% versus 6%; P = 0.002). When compared with eyes that had anterior PVR, eyes with posterior PVR had a better outcome at the 6-month postoperative examination: complete attachment of the retina (76% versus 62%; P = 0.04), visual acuity of 5/200 or better (64% versus 45%; P = 0.006), and normal intraocular pressure (86% versus 71%; P = 0.04). For eyes with anterior PVR, significant predictors of poor (< 5/200) visual acuity were a preoperative PVR grade D-1 or worse and the use of C3F8 gas as the intraocular tamponade. CONCLUSION: The Silicone Study classification of anterior PVR permits greater specificity in characterizing PVR and is prognostic of anatomic and vision outcome. Eyes with anterior PVR and clinically significant posterior PVR changes had a better visual prognosis if silicone oil was used. With the current understanding of the pathoanatomy of anterior PVR and the recent development of new surgical techniques, the incidence of anterior PVR in eyes that previously underwent vitrectomy may decline, and the prognosis in eyes with anterior PVR may improve.

Adult↗
PubMed1996

Magnetic resonance imaging of the brain in Aicardi's syndrome. Report of 20 patients.

Aicardi's syndrome consists of multiple anomalies of the eye, brain, and axial skeleton in females, and is associated with early-onset infantile spasms and severe developmental delay. For the present study, magnetic resonance images of 20 patients with Aicardi's syndrome were obtained and the neuroimaging findings catalogued. These were compared to previously reported results and the findings correlated with current theories of fetal brain development. The results revealed a high frequency of cortical migration defects (94%) and a wide variability in the callosal defect, migrational abnormalities, and other findings in Aicardi's syndrome.

Abnormalities, Multiple↗
PubMed1996

Hypericin inhibits cell growth and induces apoptosis in retinal pigment epithelial cells: possible involvement of protein kinase C.

Proliferative vitreoretinopathy (PVR) is characterized by the proliferation and migration of retinal pigment epithelial (RPE) cells in the vitreous cavity. The drug hypericin, which is already in clinical use as an antidepressant, has shown promise as an antiviral and antineoplastic agent. To investigate the therapeutic potential of hypericin in PVR, we incubated RPE cells in standard medium with various serum concentrations containing 0.5 to 5 microM hypericin. In some experiments we studied the effects of hypericin in conjunction with the RPE growth stimulating cytokine tumor necrosis factor alpha (TNF-alpha). Dose-dependent inhibition of RPE cell proliferation with IC50 values of 0.7 microM and 3.3 microM in 1% and 5% serum respectively, was found. Even in conjunction with TNF-alpha, hypericin inhibited RPE proliferation with an IC50 value of 1.5 microM. The drug inhibited PKC activity in cells treated with a 2.5 microM dose by 72% after 30 min and by 100% after 180 min. Finally, hypericin induced RPE cells to undergo apoptotic cell death, as shown by the presence of DNA laddering. These results suggest that hypericin may have potential as a therapeutic drug for PVR and that its antiproliferative and apoptotic effects on RPE cells in vitro are in part mediated by PKC.

Animals↗
PubMed1996

Induction of intercellular adhesion molecule-1 by tumor necrosis factor-alpha through the 55-kDa receptor is dependent on protein kinase C in human retinal pigment epithelial cells.

PURPOSE: To determine second messenger signaling pathways associated with tumor necrosis factor-alpha (TNF)-mediated induction of intercellular adhesion molecule (ICAM)-1 expression on human retinal pigment epithelial (HRPE) cells, a cell type known to express only the 55-kDa TNF receptor (TNFR p55). METHODS: SV 40-immortalized HRPE (SVRPE) cells were exposed to TNF with and without pretreatment with the protein kinase C (PKC) inhibitor calphostin C or the protein kinase A (PKA) inhibitor H8. SV40-immortalized HRPE cells also were treated with the PKC activator phorbol 12-myristate 13-acetate (PMA) or with the PKA activators forskolin plus 3-isobutyl-1-methyl-xanthine or dibutyryl cyclic adenosine monophosphate (cAMP) alone. Membrane fractions from untreated and treated SVRPE cells were assayed for PKC activity, and whole cell lysates were assayed for cAMP accumulation and PKA activity. Flow cytometry was performed on SVRPE cells using a monoclonal antibody specific to ICAM-1. RESULTS: Activation of TNFR p55 on SVRPE cells with TNF resulted in a rapid increase of PKC activity at 1 minute, with a subsequent downregulation to baseline. There was no increase in intracellular cAMP accumulation or PKA activity within the first 10 minutes; however, both increased within 30 minutes and returned to baseline within 1 hour. SV40-immortalized HRPE cells treated with TNF for 1 hour showed maximal induction of ICAM-1 expression at 18 hours. ICAM-1 induction by TNF treatment was inhibited by calphostin C pretreatment and not by H8 pretreatment. Protein kinase C activation with PMA for 3 hours was sufficient to induce ICAM-1 on SVRPE cells at 18 hours, whereas treatment with the PKA activators forskolin or dibutyryl cAMP did not induce ICAM-1 expression. CONCLUSIONS: Tumor necrosis factor sequentially activates the PKC and PKA pathways in SVRPE cells by way of the TNFR p55. The PKC pathway in necessary for TNF-mediated ICAM-1 upregulation, and specific activation of the PKC pathway with PMA is sufficient to induce ICAM-1 on these cells. SV40-immortalized HRPE cells may serve as a model in which to study further the functional signaling pathways associated with TNFR p55.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Effect of intravitreal administration of indomethacin on experimental subretinal neovascularization in the subhuman primate.

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 micrograms/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 < .05) in the group treated with indomethacin (14.3%, eight of 56 lesions) than in the control group (37.5%, 12 of 32 lesions). After 8 weeks, no fluorescein leakage was found in either the control or indomethacin-treated groups. Scar formation was found on histologic examination in both groups. No histologic evidence of indomethacin toxicity was seen in the adjacent retina. 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.

Animals↗
PubMed1995

Pericytes of newly formed vessels in experimental subretinal neovascularization.

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.

Animals↗
PubMed1995

Vessel formation by choroidal endothelial cells in vitro is modulated by retinal pigment epithelial cells.

OBJECTIVE: To elucidate the mechanism of bovine choroidal endothelial (BCE) cell angiogenesis and, in particular, the role of retinal pigment epithelial (RPE) cells by use of an in vitro coculture assay system. METHODS: The BCE cells were isolated from choroidal tissues and cultured. They were embedded in type I collagen gel and incubated. The gel-embedded BCE cells were then covered with a monolayer of RPE cells, pericytes, choroidal fibroblasts, or additional BCE cells on culture day 0 or day 14. The BCE cells in culture formed a meshwork of tubelike structures. The length of the tubelike structures (micrometers per field) was quantified by image analysis, as an indicator of angiogenesis. The effect of RPE cells on normal and growth-arrested BCE cell tube formation was evaluated in this assay system. The mechanism of RPE-induced angiogenesis was studied by parallel experiments with the use of neutralizing antibodies against specific growth factors (basic fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor beta). RESULTS: Ultrastructural analysis revealed that the tubelike structures had features typical of choroidal endothelial cells. Cocultures initiated on day 0 revealed that BCE cell angiogenesis was promoted by overlying RPE cells and, to a lesser extent, by pericytes, choroidal fibroblasts, and additional BCE cells when compared with BCE cells without covering cells. In cocultures initiated after BCE tube formation (day 14), there was inhibition of BCE angiogenesis by overlying RPE cells when compared with cultures without overlay or with an overlay of BCE cells. The RPE cells stimulated tube formation of growth-arrested BCE cells less effectively than did normal BCE cells. Neutralizing antibody for basic fibroblast growth factor and vascular endothelial growth factor, but not transforming growth factor beta, inhibited control and RPE-induced tube formation by BCE cells. CONCLUSIONS: Overlying RPE cells stimulate the formation of tubelike structures by choroidal endothelial cells more effectively than do fibroblasts or pericytes but inhibit BCE tube formation in older cultures. The effect involves endothelial proliferation and differentiation. The stimulatory effect of overlying RPE cells can be inhibited by neutralizing antibodies to vascular endothelial growth factor and basic fibroblast growth factor, which suggests that these growth factors play an important role in this phenomenon.

Animals↗
PubMed1995

The incidence of corneal abnormalities in the Silicone Study. Silicone Study Report 7.

OBJECTIVE: To determine factors that were prognostic of corneal abnormalities in eyes following surgery for severe proliferative vitreoretinopathy. DESIGN: Subgroup analysis of the Silicone Study. SETTINGS: Community and university-based ophthalmology clinics. MATERIALS: Eyes with attached maculae at the 24-month follow-up examination that did not have a pre-existing corneal abnormality. INTERVENTIONS: Vitrectomy surgery with long-acting gas or silicone oil. OUTCOME MEASURES: Epithelial and/or stromal edema, corneal opacity and/or previous corneal transplant. RESULTS: The incidence of corneal abnormalities at 24 months was 27% and did not differ significantly between treatment groups. Prognostic factors were preoperative aphakia or pseudophakia (P = .003), preoperative iris neovascularization (P = .006), reoperation (P = .001), the absence of a fluid/gas exchange (P = .03), corneal touch by silicone oil (P = .02), and the presence of aqueous cells (P = .009) or aqueous flare (P = .08). In a multivariate analysis, independent prognostic factors were iris neovascularization (relative risk [RR] = 13.1), aphakia or pseudophakia (RR = 3.0), postoperative aqueous flare (RR = 5.4), and reoperations (RR = 3.4). Corneal abnormalities were correlated with poor visual acuity and hypotony (P < .001). CONCLUSIONS: To our knowledge, this is the first study to document that the incidence rates of corneal abnormalities are equivalent between oil and gas. The incidence of corneal abnormalities in gas-filled eyes was higher than expected, and remained high in oil-filled eyes, despite the use of an inferior iridectomy. Successful surgical repair of the retinal detachment with a single operation, and prevention and early management of corneal touch by silicone oil should help to prevent corneal abnormalities. If rubeosis iridis or severe aqueous flare is present, preoperative treatment with intense topical and possibly periocular steroids might reduce inflammation, which might mediate corneal damage.

Adult↗
PubMed1995

beta-Galactosidase transgene expression in transplanted rabbit retinal pigment epithelial cells in vivo.

BACKGROUND: Intraocular transplantation of genetically modified cells that release a particular substance could have a major impact on the treatment of various ocular diseases. We studied the expression of the reporter gene beta-galactosidase (lacZ) in transplanted retinal pigment epithelial (RPE) cells in vivo. METHODS: RPE cells from pigmented rabbits were transduced with the beta-galactosidase gene in a retroviral vector. Cells were then assayed for gene expression and transplanted subretinally into the eyes of New Zealand White rabbits. RPE cells that were transduced with a similar vector without the beta-galactosidase gene were used as controls. Rabbits were killed on days 1, 7, and 21 and the eyes processed for transmission electron microscopy RESULTS: Neomycin-resistant rabbit RPE cells that showed beta-galactosidase activity were generated within 2-5 weeks. After transplantation, viable RPE cells that expressed the transgene and that phagocytosed rod outer segments were observed on days 1, 7, and 21 CONCLUSIONS: The results show that generation of genetically modified RPE cells is feasible and that the transplanted cells remain viable and continue to express the transgene in the subretinal space of the host animal for at least 21 days. Transplantation of such genetically modified RPE cells could provide a new tool for studying retinal diseases and, potentially, for correcting metabolic abnormalities in retinal degenerations and dystrophies.

3T3 Cells↗