Biomedical subjects

S J Ryan

Publications and source records attributed to S J Ryan.

At least 73 records · Page 4Linked to original sources

PubMed1995

Migration of retinal pigment epithelium cells in vitro is regulated by protein kinase C.

The migration of retinal pigment epithelial (RPE) cells is an important step in various pathologic conditions, including subretinal neovascularization (SRN) and proliferative vitreoretinopathy (PVR). Therefore, elucidation of the mechanism of RPE migration may be useful in devising effective treatment for these disorders. Since protein kinase C (PKC) has been shown to regulate the migration of other cell types, we studied the effects of PKC agonists and antagonists on RPE migration. We used an in vitro wound healing model in which a small area of a confluent monolayer of bovine RPE cells was denuded with a razor blade. The cultures were subsequently incubated with agents known to stimulate [phorbol 12-myristate 13-acetate (PMA)] or inhibit (calphostin C, staurosporine) PKC. After 20 hr, migration was measured as the number of cells that had entered the denuded area. We also measured the translocation of PKC from the cytosol to the membrane in order to determine the activation or inhibition of PKC by PMA and calphostin C in the cells. The phorbol ester PMA stimulated migration by 41%, and calphostin C and staurosporine inhibited migration by 38% and 31%, respectively, in a medium supplemented with 10% serum. To determine the requirement for serum in this modulation, we also measured the effects of PMA and calphostin C on RPE migration in serum-free medium. Under these conditions, basal migration was greatly decreased, but PMA stimulated migration by 177% and calphostin C inhibited migration by 93%. Since PKC modulation is known to induce the proliferation of cells, we also tested the effects of these agents on growth-inhibited migration by pretreating the cells with the antiproliferative drug mitomycin C. We found that modulation of PKC under these conditions equally affected growth-inhibited and growth-dependent migration. Therefore, based on the increase in RPE migration induced by a PKC agonist, and the decrease in migration caused by PKC antagonists, it is suggested that PKC-mediated signal transduction plays a crucial role in RPE cell migration. This knowledge may be useful in devising effective treatments for SRN and PVR.

Alkaloids↗

PubMed1995

Inhibition of experimental proliferative vitreoretinopathy by retroviral vector-mediated transfer of suicide gene. Can proliferative vitreoretinopathy be a target of gene therapy?

PURPOSE: To determine the potential of somatic gene transfer as a treatment for proliferative vitreoretinopathy (PVR), experimental PVR was induced in rabbits by intraocular injection of fibroblasts bearing the herpes simplex virus thymidine kinase (HStk) gene. These transduced cells should be susceptible to cytotoxicity by exposure to ganciclovir (GCV). MATERIALS AND METHODS: Rabbit fibroblasts were transduced with retroviral vectors bearing an HStk gene. Proliferative vitreoretinopathy was induced by injection of 5 x 10(4) normal or HStk gene-transduced fibroblasts (HStk fibroblasts) into rabbit eyes. Ganciclovir (100 micrograms per eye) or saline was injected into the vitreous on days 0 and 4. Experimental animals were divided into three groups: group A received HStk fibroblasts with GCV; group B, normal fibroblasts with GCV; group C, HStk fibroblasts with saline. Proliferative vitreoretinopathy also was induced in several other groups of eyes, some receiving GCV and different proportions of HStk fibroblasts to normal fibroblasts, others receiving only normal fibroblasts and GCV. The eyes were examined by indirect ophthalmoscopy on days 4, 7, 14, and 28, and PVR was classified into six stages (0-5). RESULTS: Proliferative vitreoretinopathy was induced and progressed over time in each group. On day 28, PVR was most severe in animals in group B (average stage, 4.6) and group C (average stage, 4.4). Proliferative vitreoretinopathy was inhibited in group A (average stage, 1.0). The groups that received mixed injection of HStk fibroblasts and normal fibroblasts had intermediate PVR. Results of histologic study showed no apparent toxic or pathologic reaction in the retinochoroidal tissue of group A animals. CONCLUSIONS: Severity of experimental PVR clearly was reduced by transfer of the HStk gene and administration of GCV. This inhibitory effect also was produced by a combination of 10% HStk fibroblasts and 90% normal fibroblasts, indicating a significant bystander effect. These data suggest the potential of somatic gene therapy for the treatment of PVR.

Animals↗

PubMed1995

Cranial arteriopathy in familial Vogt-Koyanagi-Harada syndrome.

A 59-year-old woman with Vogt-Koyanagi-Harada (VKH) syndrome presented with transient ischemic attacks. Magnetic resonance angiography showed multiple areas of stenosis affecting the intracranial portions of both internal carotid arteries. Conventional angiography confirmed these abnormalities and also demonstrated tapering stenosis of the extracranial segment of the left internal carotid artery. This patient and her similarly affected daughter represent the first reported association between cranial arteriopathy and intergenerational passage of VKH syndrome.

Carotid Artery, Internal↗

PubMed1995

Inhibition of experimental proliferative vitreoretinopathy in rabbits by suramin.

Proliferative vitreoretinopathy (PVR) is the most common cause for failure of retinal reattachment surgery. In a search for better pharmacologic treatment of PVR, we investigated the effect of intravenous injections of suramin on an experimental rabbit model of PVR. PVR was induced in rabbits by intravitreal injection of autologous fibroblasts. The experimental group (7 eyes) received intravenous injections of suramin (100 mg/kg body weight) every 3 days for 15 days, beginning 3 days before fibroblast injection. The control group (5 eyes) was treated similarly but received intravenous saline solution in place of suramin. A third group (4 eyes) received suramin according to the protocol above but did not receive intravitreal fibroblasts. The animals were examined by indirect ophthalmoscopy every 3 days and were sacrificed 14 days after the injection of fibroblasts. The serum levels of suramin were evaluated by high-performance liquid chromatography. The PVR was classified as stages I-V, based upon clinical findings. PVR developed in both experimental and control animals but was less severe in those treated with suramin. On day 14, the average stage of PVR in the control group was 3.8; in the suramin-treated group, however, the average stage was 2.4, which was significantly less than in the control group (p < 0.02). None of the rabbits in the third group showed pathologic changes. Serum levels of suramin were maintained at an average of 280.2 micrograms/ml and no apparent toxicity was found in the retina by histologic study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

In vitro studies of human choroidal endothelial cells.

Vascular endothelial cells play an important role in progression or healing of various retinal or choroidal diseases and they have a broad organ specificity. We have grown and studied human choroidal endothelial cells (CECs) cultured in a collagen gel, where they form tube-like structures. CECs were differentially isolated from choroidal tissues and cultured to near homogeneity. The cells were embedded in a type I collagen gel in 24-well culture dishes and incubated with M199 medium containing 10% fetal calf serum. Gels were observed using phase contrast microscopy and were evaluated histologically by light and electron microscopy. The CECs were strongly positive for factor VIII-related antigen and actively ingested diI-acetylated LDL, indicating their endothelial nature. Ultrastructural analysis of the tube-like structures revealed a central lumen surrounded by cells joined apically by junctions and showing prominent pinocytotic activity, fenestrations and basement membrane formation; these features are typical of CECs in vivo. This preparation should be a useful tool to study the development of physiology and pathology of choroidal endothelium.

Carbocyanines↗

PubMed1995

Thrombin induced cytoskeletal change in cultured bovine corneal endothelial cells mediated via protein kinase C pathway.

We studied the participation of the protein kinase C pathway in thrombin-induced cytoskeletal alterations in confluent cultured bovine corneal endothelial (BCE) cells. Cultured BCE cells were exposed to alpha-thrombin (0.1-10 U/ml for 15-60 min) and the distribution of F-actin and vinculin plaques was examined using immunofluorescent staining and electron microscopy. Phorbol 12-myristate 13-acetate (PMA, 10 nM for 15 min), the broad spectrum protein kinase inhibitors staurosporine (10 nM) and H-7 (10 nM), and highly specific PKC inhibitor calphostin C (10 nM) were used to evaluate the role of PKC/phosphorylation in this phenomenon. HA-1004 (10 nM) was used as a negative control for these inhibitors. In a parallel experiment, PKC activity of cytosol and membrane of BCE cells was also evaluated. In control samples, F-actin was distributed mainly at the periphery of cells, where it formed dense peripheral bundles; vinculin plaques were also present at the cell boundary. Exposure of BCE cells to thrombin changed the distribution of F-actin and vinculin into a diffuse pattern; a similar alteration was also induced by incubation with PMA. These phenomena were blocked by incubation with H-7, staurosporine and calphostin C. Both cytosolic and membrane PKC activity was increased after 5 to 30 min exposure of alpha-thrombin and returned to the control level after 1 h. alpha-Thrombin induces alteration in the cytoskeleton of BCE cells, and this message is transduced at least in part by PKC dependent pathways. PKC/phosphorylation may thus play an important role in physiological processes that involve alterations of the cytoskeleton.

Actins↗

PubMed1995

SV40-immortalized and primary cultured human retinal pigment epithelial cells share similar patterns of cytokine-receptor expression and cytokine responsiveness.

Retinal pigment epithelial (RPE) cells produce and respond to a variety of cytokines; however, molecular and biochemical studies are restricted by the limited access to large numbers of pure cells and the variability associated with different donor sources. Despite success in establishing primary human RPE (HRPE) cell cultures, the inability to sustain consistent proliferation rates and morphology over several passages remains a concern. This problem was approached by using an immortalized line of simian virus (SV)40 transformed fetal HRPE cells (SVRPE). Cytokine production, receptor expression and responsiveness in the SVRPE cell line was analyzed to determine the usefulness of this model for studying HRPE-cytokine interactions. Using reverse transcriptase polymerase chain reaction (RT-PCR), HRPE and SVRPE cells demonstrated an identical pattern of interleukin-1 receptor (IL-1R), IL-2R (alpha sub-unit), IL-6R, interferon (IFN)-gamma R and tumor necrosis factor-alpha (TNF)R p55 expression. No amplification products for TNFR p75 or granulocyte/macrophage colony stimulating factor (GM-CSF)R were demonstrated in either population. IFN-gamma stimulation induced surface human leukocyte antigen (HLA)-DR in both SVRPE and HRPE, while TNF treatment induced surface expression of intercellular adhesion molecule (ICAM)-1 on SVRPE and upregulated ICAM from basal levels on HRPE. Both cell types showed amplification products for interleukin (IL)-1 beta, IL-6 and transforming growth factor (TGF)-beta 1 using RT-PCR. The bioassays demonstrated that both populations of unstimulated cells constitutively secrete very low levels of TGF-beta and no IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1995

Effect of tecogalan sodium on angiogenesis in vitro by choroidal endothelial cells.

PURPOSE: To examine the possible inhibitory effect of tecogalan sodium, derived from bacteria, on three important components of in vitro angiogenesis (endothelial proliferation, migration, and tube formation in a collagen gel) using bovine choroidal endothelial cells (CECs). METHODS: The effects of tecogalan sodium (1, 5, 25, 125, and 250 micrograms/ml) on cultured CECs were examined when basic fibroblast growth factor (bFGF, 10 ng/ml), vascular endothelial growth factor (VEGF, 50 ng/ml), a combination of bFGF (10 ng/ml) and VEGF (50 ng/ml) (bFGF/VEGF) and 10% fetal calf serum (FCS) were used as angiogenic stimulants. For the proliferation assay, CECs were cultured and the cell numbers counted on days 1, 3, and 5. For migration assay, CECs were seeded in the upper half of a Boyden chamber while an angiogenic growth factor was loaded in the lower half. After 6 hours of incubation, cell migration was evaluated by counting the numbers of migrated cells per microscopic field on the lower side of the filter. For the tube-forming assay, CECs were seeded in a type I collagen gel, and the length of the tube-like structures (an indicator of angiogenesis) formed by CECs per microscopic field was quantified by image analysis. The effect of neutralizing antibody for bFGF also was tested in these three assays. RESULTS: All tested angiogenic stimulants induced CEC proliferation. The stimulatory effect of bFGF and bFGF/VEGF was reduced by tecogalan sodium (IC50 for bFGF effect, 26.1 micrograms/ml). However, the effect of VEGF and of 10% FCS was not altered by low doses of tecogalan sodium (< 25 micrograms/ml). Chemotaxis of CECs was stimulated by bFGF alone and by bFGF/VEGF, and this effect was inhibited by tecogalan sodium (IC50 for bFGF, 3.2 micrograms/ml). Stimulation of chemotaxis by VEGF alone and by 10% FCS was not affected by tecogalan sodium in low doses but was inhibited by high doses. Tube formation was stimulated by administration of each of the factors. Stimulation of tube formation by bFGF and by bFGF/VEGF was inhibited by tecogalan sodium (IC50 for bFGF, 18.2 micrograms/ml). High doses of tecogalan sodium (125 and 250 micrograms/ml) also inhibited 10% FCS-induced proliferation, migration, and tube formation. CONCLUSION: bFGF, VEGF, and a combination of bFGF and VEGF stimulated proliferation, migration, and tube formation by CECs in vitro. These stimulatory effects, but especially those of bFGF, were inhibited by tecogalan sodium. If tecogalan sodium can be shown to have a similar effect in vivo, it might have the potential for pharmacologic control of subretinal neovascularization.

Animals↗

PubMed1995

[Long-term follow-up of allotransplantation of retinal pigment epithelial cells in rabbit with special reference to morphological studies].

Dysfunction as well as pathological changes of retinal pigment epithelium (RPE) has been implicated as the causes of some retinal diseases, including age-related macular degeneration, hereditary macular degeneration and retinitis pigmentosa, etc. Transplantation of normal healthy RPE cells with an attempt to treat the retinal diseases is one of the current interests in ophthalmic research. We have developed a modified pars plana technique including vitrectomy for subretinal transplantation of homologous, cultured, natural pigment labelled RPE cells in the non-pigmented rabbit. Our results, with follow-up from one week to one year, revealed that the transplanted RPE cells not only survived and attached to Bruch's membrane of the host eyes, but also had a distinct basal and apical morphology as seen in close contact with host photoreceptors, and formed junctional complexes with neighboring RPE cells. Close contact between the microvilli of the grafted RPE cells and the photoreceptor outer segments of the host was also observed. The normal periodical sheddings of the host outer segments were phagocytosed by the transplanted RPE cells, as demonstrated in our results. Furthermore, there was practically no, if any, sign of rejection found. All the results have demonstrated that the transplantation of RPE cells in rabbits was successful and these observations provide a reliable experimental evidence for the clinical research of allotransplantation of RPE cells.

Animals↗

PubMed1995

A new model of subretinal neovascularization in the rabbit.

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 micrograms 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.

Animals↗

PubMed1994

The effects of silicone oil removal. Silicone Study Report 6.

OBJECTIVE: To evaluate the advisability of removing silicone oil from eyes after surgery for severe (with a classification of at least C-3) proliferative vitreoretinopathy. DESIGN: Subgroup analysis of the Silicone Study, a randomized, multicentered, surgical trial. SETTING: Community- and university-based clinics. PATIENTS: Two hundred twenty-two eyes with severe proliferative vitreoretinopathy followed up in the Silicone Study. INTERVENTIONS: Vitrectomy for proliferative vitreoretinopathy with silicone oil as the intraocular tamponade. OUTCOME MEASURES: Changes in visual acuity, recurrent retinal detachment, and incidence of complications. RESULTS: Ninety-nine (45%) of 222 eyes had surgery for silicone oil removal (oil-removed eyes). Compared with the eyes that did not undergo silicone oil removal (oil-retained eyes) evaluated at a comparable time after oil injection, oil-removed eyes at the examination prior to oil removal were more likely to be attached (85% vs 40%; P < .0001), have a visual acuity of 5/200 or greater (63% vs 35%; P < .0001), and not be hypotonous (5% vs 22%; P < .001). There was no association between the length of oil retention and incidence of recurrent retinal detachment after oil removal. Eyes with attached retinas at the time of oil removal generally improved in visual acuity at the last follow-up examination (P < .0001), which was not evident in eyes with detached retinas at the time of oil removal. In a matched-pair cohort analysis comparing both sets of eyes, there was an increased risk for recurrent retinal detachment at the last follow-up examination in the oil-removed eyes (odds ratio [OR], 2.1; P = .09). However, overall visual acuity improved for oil-removed eyes in 19 (29%) of 66 pairs and for oil-retained eyes in one (2%) of 66 pairs (OR, 19.0; P < .0001). Although nonsignificant, incidence rates of keratopathy (OR, 0.5) and hypotony (OR, 0.5) were lower in oil-removed eyes. CONCLUSION: Removal of silicone oil in anatomically successful eyes significantly increases the likelihood of improved visual acuity with a slight increase in the likelihood of recurrent retinal redetachment. There was a trend for a reduction in the incidence of complications in the oil-removed eyes.

Adult↗

PubMed1994

Subretinal neovascularization in the rat induced by IRBP synthetic peptides.

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.

Amino Acid Sequence↗

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

Magnetic resonance imaging in ochronosis, a rare cause of back pain.

A 34-year-old man had progressive, poorly controlled low back pain for 3 years before testing confirmed a diagnosis of ochronosis. This is the first case description of the magnetic resonance imaging (MRI) appearance of spinal ochronosis, which should be considered when advanced degenerative change is seen on spinal MRI in young individuals.

Adult↗

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

Collagen gel contraction induced by retinal pigment epithelial cells and choroidal fibroblasts involves the protein kinase C pathway.

Contraction of intraocular fibrous membranes is an important feature in the pathogenesis of retinal detachment in proliferative vitreoretinopathy (PVR). Collagen gel contraction is a useful in vitro model of membrane contraction in PVR. We studied the role of protein kinase C (PKC) in collagen gel contraction induced by bovine choroidal fibroblasts and retinal pigment epithelial (RPE) cells. Collagen gels embedded with the cells were formed in culture dishes and gel contraction was evaluated. The PKC stimulator, phorbol 12-myristate 13-acetate (PMA), and the protein phosphatase 1 and 2A inhibitor, okadaic acid (OA), were used to evaluate the role of the PKC-mediated phosphorylation system in this gel contraction. Fifteen min incubation with PMA stimulated gel contraction, but 180 min incubation had no effect. Choroidal fibroblast- but not RPE cell-induced gel contraction was stimulated by OA. These effects were inhibited by the broad spectrum protein kinase inhibitor staurosporine and the specific PKC antagonist calphostin C. Transforming growth factor-beta (TGF-beta)1 and TGF-beta 2, which are known to be present in eyes with PVR, were evaluated to determine their effect on gel contraction. Both TGF-beta 1 and 2 had a stimulatory effect on contraction of gels seeded with choroidal fibroblasts and RPE cells, but staurosporine and calphostin C inhibited this TGF-beta-induced gel contraction. These results indicate that activation of PKC/protein phosphorylation is an important factor in gel contraction caused by choroidal fibroblasts and RPE cells, and that TGF-beta-induced gel contraction is mediated at least in part via the PKC pathway.

Animals↗

PubMed1994

Cytokine effect on fibronectin release by retinal pigment epithelial cells.

Because fibronectin (FN) is known to be present in membranes in proliferative vitreoretinopathy, we sought to identify cytokines that regulate the release of FN by retinal pigment epithelial cells (RPE). Levels of FN in the supernatant of cultured human RPE cells were quantified with an ELISA, after which the cells were stimulated with human recombinant cytokines, interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interferon gamma (IFN-gamma), transforming growth factor beta 1 and 2 (TGF-beta), and phorbol myristate acetate (PMA). Protein kinase C (PKC) was blocked by 2 nM calphostin C or 1 mM staurosporine. RPE cells released FN into the supernatant constitutively. TGF-beta 1 and TGF-beta 2 upregulated the FN release in a dose- and time-dependent manner. The other cytokines tested were without effect. In combination, IFN-gamma and IL-1 beta reduced the effect of TGF-beta. PMA, which is a PKC activator, also increased the release of FN in a dose-dependent manner. Blocking of PKC with specific inhibitors abolished the effects of TGF-beta and PMA. The results show that TGF-beta is a potent stimulator of FN release by RPE cells, and exerts its effects via signal transduction involving PKC. Its effect is reduced by IFN-gamma.

Cells, Cultured↗

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↗