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Biomedical subjects

I Grierson

Publications and source records attributed to I Grierson.

At least 19 recordsLinked to original sources
PubMed1992

Local production of fibronectin by ectopic human retinal cells.

The distribution of fibronectin mRNA and fibronectin in adult human retina and epiretinal membranes was investigated by in situ hybridisation and immunohistochemical techniques. The cells in normal adult retina contained little or no fibronectin mRNA and the retina only showed fibronectin immunoreactivity in retinal vessels. The cells in detached neuroretina did not contain fibronectin message but the vitreoretinal interface of the detached retina exhibited variable fibronectin immunoreactivity. Retinal glia, retinal pigment epithelium and fibroblast-like cells in membranes at the vitreoretinal juncture (epiretinal membranes) showed variable labelling with the fibronectin mRNA probe and all the membranes immunostained for fibronectin. No difference could be detected between membrane cell types in the intensity of labelling with the mRNA probe or for fibronectin immunoreactivity. The results indicate that cells in situ in attached and detached adult human retina do not produce fibronectin. Although fibronectin at the vitreoretinal juncture in retinal detachment is probably partly derived from plasma fibronectin resulting from breakdown of the blood-retinal barrier, ectopic retinal cells produce fibronectin and contribute to the glycoprotein epiretinal membranes.

Adolescent↗
PubMed1992

Intraoperative and post operative treatment with 5-fluorouracil and mitomycin-c: long term effects in vivo on subconjunctival and scleral fibroblasts.

Rabbits undergoing full thickness glaucoma filtering surgery were exposed to one of 4 treatments. Group 1 received intraoperative distilled water, group 2 received intraoperative mitomycin-c 0.2 mg/ml for 5 minutes, group 3 received 5 post operative injections of 5-Fluorouracil (5-FU) 5 mg in 0.1 ml, and group 4 received intraoperative 5-FU 50 mg/ml followed by 5 post operative injections of 5-FU. 30 days after the operation tissue biopsies were taken from the subconjunctival and scleral tissue at the treated area and 90 and 180 degrees from the treated area. The biopsies were then placed in tissue culture media and the outgrowths quantitated. The fibroblast outgrowths from all areas did not differ significantly from each other except for the outgrowths from the areas directly treated with mitomycin 0.2 mg/ml which were significantly smaller. In addition then cells were morphologically abnormal although there were foci of normal cells which appeared to be growing from localised areas in the tissue biopsies. The outgrowths from the areas 90 and 180 degrees from the treated area were normal. Intraoperative treatments with mitomycin-c result in long term inhibition of fibroblast proliferation limited to the treated area, when compared with intraoperative and postoperative treatment with 5-FU. Failure of filtration surgery in eyes treated with intraoperative mitomycin may in part be due to unaffected cells reproliferating.

Animals↗
PubMed1992

Proliferative vitreoretinopathy. Lymphocytes in epiretinal membranes.

BACKGROUND: To investigate the potential contribution of inflammatory and immune-mediated processes contributing to the pathogenesis of proliferative vitreoretinopathy (PVR), an immunohistochemical study was undertaken to characterize the infiltrating inflammatory cells in epiretinal membranes surgically removed from the eyes of patients with PVR. METHODS: Twenty-one epiretinal membranes obtained surgically from eyes with PVR complicating rhegmatogenous retinal detachment were studied immunohistochemically using the ABC technique and a panel of monoclonal and polyclonal antibodies. RESULTS: T lymphocytes were found in 18 of the 21 specimens and generally constituted a small percentage of the total cell number. CD4+ T cells were found in 14 of the 18 membranes containing T cells. Three of six frozen membranes contained T cells that were positive for the interleukin-2 receptor. In 5 of 16 membranes studied, cells positive for the macrophage/monocyte marker were found. No B lymphocytes or neutrophils were identified, and there were no deposits of complement or immunoglobulins. Positive staining for the class II MHC antigen HLA-DR was found in 7 of the 21 membranes, a result that was more consistent in frozen than in fixed tissues. CONCLUSION: The study suggests that T lymphocytes are present in PVR epiretinal membranes and may be activated. These cells have the potential to play a role in the pathobiology of PVR.

Cell Membrane↗
PubMed1992

Thrombospondin as a component of the extracellular matrix of epiretinal membranes: comparisons with cellular fibronectin.

We compared the distribution of the adhesive extracellular matrix glycoproteins thrombospondin and cellular fibronectin in epiretinal membranes. A total of nine membranes were investigated with immunohistochemical techniques. Thrombospondin and cellular fibronectin immunoreactivity were observed in seven of the specimens and immunostaining for the two glycoproteins was co-localised in four of the membranes. The findings indicate that thrombospondin contributes to the extracellular glycoprotein content of epiretinal membranes and is frequently co-distributed with cellular fibronectin in the tissue. As a consequence, thrombospondin may play a role in the assembly of the extracellular matrix of epiretinal membranes.

Diabetic Retinopathy↗
PubMed1992

The chemoattractant activity of the vitreous to human scleral fibroblasts following retinal detachment and proliferative vitreoretinopathy.

The results are presented of a migration assay of scleral fibroblasts to 25% diluted vitreous samples from 27 patients with complex retinal detachments divided into three groups: group 1, no proliferative vitreoretinopathy (PVR); group 2, early PVR; and group 3, advanced PVR. There was a statistically significantly greater migration with vitreous samples from group 3 than with group 1 (p less than 0.0001) but no significant correlation for migration with the age of patients, duration of retinal detachment, or number of retinal procedures undertaken. Analysis of vitreous by gel electrophoresis showed that cellular migration was proportional to the number of peptide bands. Vitreous fibronectin levels were measured and there was a positive correlation between fibronectin in the vitreous samples and the migration of fibroblasts to the vitreous (r = 0.68, p less than 0.004).

Adult↗
PubMed1992

Fibronectin synthesis in subretinal membranes of proliferative vitreoretinopathy.

In situ hybridisation and immunohistochemical studies were conducted on six surgically excised subretinal membranes of proliferative vitreoretinopathy to investigate whether displacement of retinal pigment epithelial and glial cells to subretinal membranes was associated with fibronectin production by the subretinal membrane cells. Fibronectin messenger RNA (mRNA) and fibronectin immunoreactivity were observed in some cells in all of the subretinal membranes studied and up to 30% of the cells in individual specimens showed intense labelling for fibronectin mRNA. The results support the concept that the cells in subretinal membranes produce fibronectin. Locally produced fibronectin may play a role in subretinal membrane cohesion, and displacement of retinal pigment epithelial and glial cells from their normal location may induce the cells to manufacture fibronectin. Fibronectin production may be more prominent in migrating subretinal cells.

Eye Diseases↗
PubMed1992

Cytokeratins and retinal epithelial cell behaviour.

The expression of cytokeratins 18 and 19 by human retinal pigment epithelial cells (HRPE) has been suspected of being associated with HRPE proliferation. We have investigated the involvement of these cytokeratin subtypes in the proliferative and migratory behaviour of cultured HRPE. Cell proliferation markers (bromodeoxyuridine and proliferating cell nuclear antigen) and the cytokeratins were identified using immunohistochemical techniques. In vitro, cytokeratins 18 and 19, as detected by the monoclonal antibodies RGE 53 and K4.62, were expressed in a subset of HRPE and this subset was significantly less likely to be proliferating. Micro-chemotaxis chambers were used to study migrating cells and immunohistochemical staining for cytokeratins 18 and 19 revealed that actively migrating cells always expressed these two cytokeratins, whereas stationary cells did not label for these cytokeratin subtypes. It was apparent that cytokeratins 18 and 19 were not markers of proliferation, but were involved in the mobility of HRPE in vitro. Cytokeratins 18 and 19 may be useful indicators of simple epithelial cell migration in tissues.

Actins↗
PubMed1992

In vitro studies of the contractility of cell types involved in proliferative vitreoretinopathy.

The contractile activity of cells in epiretinal membranes leads to retinal detachment and proliferative vitreoretinopathy, but it is unknown which cell type contributes most to this process. In this study, the relative contractility of three cell types thought to be involved in epiretinal membrane formation was measured. Bovine scleral fibroblasts (BSF), retinal pigment epithelium (BRPE) and retinal glia (BRG) were suspended in a rapidly polymerizing floating type I collagen matrix. Matrix contraction was assessed and morphologic studies were performed using light microscopy and scanning electron microscopy. BSF reached 50% contraction within 4 days and BRPE needed 7-10 days, whereas BRG showed no matrix contraction. Cell proliferation, as shown by bromodeoxyuridine labeling, did not occur in the matrix. During the period of greatest contraction, cells had formed processes but were isolated from each other. Over the 7 day period, an increasing number of cells was found on the surface of the matrix, resulting (with BSF) in an encapsulating monolayer. This monolayer developed only after most of the contraction was over. These findings suggest that BSF and BRPE reorganize the collagen matrix through a combination of individual cellular mobility and attachment to the collagen fibers. BRG's inability to attach to the collagen and reorganize its arrangement resulted in its lack of matrix contraction.

Animals↗
PubMed1992

Oxytalan fibres in proliferative vitreoretinopathy.

The distribution of elastic and related fibres was studied in 29 fibrocellular membranes associated with proliferative vitreoretinopathy using histochemical, immunohistochemical and ultrastructural techniques. Ten subretinal and ten epiretinal membranes were subjected to light microscopical investigation, whilst the remaining nine membranes were examined by transmission electron microscopy. Oxytalan fibres, an elastic fibre precursor that is found in a variety of normal and pathological connective-tissue matrices, were identified in all of the specimens. Mature elastic fibres were not observed in any of the 29 membranes. The demonstration that oxytalan connective-tissue fibres contribute to the infrastructure of PVR membranes adds further evidence to the suggestion that this proliferative tissue might be the result of a repair mechanism.

Adolescent↗
PubMed1992

The long-term effects of 5-fluorouracil and sodium butyrate on human Tenon's fibroblasts.

The use of subconjunctival 5-fluorouracil (5-FU) in the first weeks after filtration surgery may ensure long-term bleb survival despite a continuing proliferative stimulus such as in eyes with neovascular glaucoma. In addition, long-term side effects may occur, such as increasing bleb thinning. To ascertain the long-term effects of 5-FU and sodium butyrate, an agent with differentiating and antiproliferative properties, we exposed proliferating human Tenon's capsule fibroblasts to different concentrations of the drugs. The cells were exposed to 5-FU for 1-12 d. The cells were subsequently observed for up to 30 d. Cell proliferation was assessed using cell counting and bromodeoxyuridine uptake, and cell viability was assessed with trypan blue uptake. 5-FU and sodium butyrate inhibited fibroblast proliferation during the treatment period. Higher concentrations of 5-FU (100 and 1000 micrograms/ml) for as little as 1 d resulted in no significant increase in the number of fibroblasts for at least 29 d after treatment was stopped, despite continued stimulation with serum. When treatment with sodium butyrate was stopped, there was greater recovery of proliferation. At a constant concentration of 1000 micrograms/ml of 5-FU for 3 or more days, or a concentration of 100 mmol/l sodium butyrate for 12 d, the entire fibroblast population gradually died over the 30 d period. Thus, short-term treatment with 5-FU may result in long-term inhibition of proliferation of fibroblasts. Long-term inhibition depends on the duration of treatment or on the concentration of 5-FU. Short-term treatment may be affecting the ability of the tissues at the bleb site to heal in the long term. Different dosage regimens may have advantages and are discussed.

Adolescent↗
PubMed1991

Chemoattractants produced by ocular cells induce trabecular meshwork cell migration.

Media conditioned by bovine corneal endothelium and scleral fibroblasts were found to induce the migration of bovine trabecular meshwork cells. The migrational activity had both chemokinetic (stimulated random motion) and chemotactic (directional migration) components. That produced by corneal endothelial cells had a markedly more potent effect. The relevance of these in vitro studies is discussed. Biochemically stimulated migration and loss of meshwork cells may be involved in the pathogenesis of glaucoma.

Animals↗
PubMed1991

Effect of beta radiation on proliferating human Tenon's capsule fibroblasts.

The effects of different doses of beta radiation from a strontium-90 source on the proliferation of human Tenon's capsule fibroblasts were studied. The cultured fibroblasts were exposed to doses of 100, 250, 500, 750, 1000, 1500, and 3000 rads, and cell numbers were counted at days 3, 7, and 14. Treatment inhibited the proliferation of the fibroblasts. At seven days the cells exposed to 3000 rads showed a decrease relative to the starting cell numbers, and at 14 days the cells exposed to 1500 and 3000 rads showed a decrease in cell numbers. The doses of radiation which inhibited cell proliferation more than 50% (at day 7 and 14) and yet did not cause a decrease in the cell population were 500, 750, and 1000 rads. beta Radiation reduces the proliferation of human Tenon's capsule fibroblasts, and at higher doses this effect may be more pronounced one and two weeks after irradiation.

Beta Particles↗
PubMed1990

Fibronectin induces migration of bovine trabecular meshwork cells in vitro.

The migration of cultured bovine trabecular meshwork cells in response to fibronectin was studied using a 48-well migration chamber. Fibronectin was shown to be a potent chemoattractant for these cells, with a dose optimum of 30 micrograms ml-1. At this dose, the number of migrated cells was approximately 12 times that of the control, which was serum-free medium. Analysis of the migratory response revealed it to be mainly a chemokinesis, but chemotaxis was a substantial component. Electron microscopy demonstrated that adhesion and spreading of cells on the surface of the pore-containing membrane are necessary prerequisites to their migration through a pore. Microspikes are abundant during the movement of cellular processes into and through the pores. The migrated cells are extremely thin with a large surface area, but despite this phenotypic alteration the ultrastructure of migrated cells is unchanged.

Animals↗
PubMed1990

Variation in epiretinal membrane components with clinical duration of the proliferative tissue.

Immunohistochemical investigations were conducted on surgically excised epiretinal membranes to determine how cellular and extracellular components of proliferative vitreoretinopathy membranes change with time. Specimens of less than four months' duration contained a significantly higher proportion of retinal pigment epithelial cells than later membranes. No association was found between membrane duration and the content of collagen subtypes I to IV and laminin, but 'early' specimens contained significantly more fibronectin than did 'late' membranes. Fibronectin and collagens I, III, and IV showed a variable relationship with glial cells and were most consistently associated with retinal pigment epithelial and fibroblast-like cells. These observations may explain some of the surgical features of epiretinal membranes.

Cell Division↗
PubMed1990

The effect of topical dexamethasone and preoperative beta irradiation on a model of glaucoma fistulizing surgery in the rabbit.

We studied the effect of topical dexamethasone (1%) and preoperative beta irradiation on a model of glaucoma fistulizing surgery in the rabbit. Intraocular pressure and gross facility of aqueous outflow following surgery were not influenced by either treatment, although blebs persisted longer in the irradiated eyes. Steroids reduced clinically observable inflammation as well as the number of inflammatory cells identifiable by microscopy. Fibroblast production temporarily slowed, and ultra-structural examination demonstrated lipid-filled vacuoles and dilated mitochondria in these eyes. Also, the scar was thinner at 24 days. Beta irradiation delayed wound healing and the scar was thinner in the early postoperative stages, but the light microscopic appearance of the scar was unaltered at 59 days. Inflammation was more pronounced initially, with abundant fibrin in the wound. Recovery of the conjunctival epithelium was delayed. The delay in fibroblast recruitment and wound contraction, the thinner scar tissue, and the increased survival of the bleb are all factors that suggest that beta irradiation may be a useful adjunct to glaucoma surgery.

Analysis of Variance↗