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Biomedical subjects

I Grierson

Publications and source records attributed to I Grierson.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1990

Regional distribution of lysosomal enzymes in the canine retinal pigment epithelium.

We have investigated the activities of four lysosomal enzymes in RPE cells isolated from three regions of the canine fundus: the tapetal area, the central pigmented area and the peripheral area. The results obtained with freshly isolated cells showed that the activities of acid phosphatase, B-glucuronidase and N-acetyl-B-glucosaminidase were significantly higher in RPE cells derived from the peripheral region when compared to those from the two central regions. In contrast, the activity of cathepsin D was significantly higher in the tapetal region than in the periphery. The regional distribution of both acid phosphatase and B-glucuronidase observed in fresh RPE cells was progressively lost when these cells were grown in culture. Estimations of photoreceptor density per RPE cell from each of the regions indicated that the number of photoreceptors per RPE cell did not vary significantly with retinal location and suggested that variations in enzyme content were not related to differences in photoreceptor cell distribution.

Animals↗
PubMed1989

Chemotactic activity of aqueous humor. A cause of failure of trabeculectomies?

The chemoattractant activity for ocular fibroblasts of the aqueous humor of patients undergoing glaucoma surgery was evaluated in 48-well microchemotaxis chambers and compared with control specimens from patients undergoing cataract extractions. All specimens were chemoattractant, but those from patients who had previously undergone glaucoma surgery that had failed were of significantly greater activity than the controls'. This chemoattractant activity is primarily chemotactic. It consists of heat-stable and heat-labile components. The predisposition of a patient to sustain failed glaucoma drainage surgery may be related to the chemoattractant activity of his aqueous humor, since strongly chemoattractant aqueous humor may encourage fibrosis at the operation site.

Animals↗
PubMed1989

Partial characterization of the fibroblast chemotactic constituents of human aqueous humour.

This study demonstrates that aqueous humour derived from patients undergoing cataract extraction contains chemoattractants for ocular fibroblasts. The chemoattractant activity is independent of the surgical approach to obtaining the specimen as well as the surgeon operating. Studies in rabbits demonstrate that the chemoattractant activity is not artefactually produced by aqueous sampling and confirm the integrity of the blood-aqueous barrier. Substances responsible for this activity have molecular weights greater than 30,000; they are deactivated by low pH but retain activity at high pH. Identification of the chemoattractants in aqueous humour may allow pharmacological manipulation of would healing in relation to trabeculectomies.

Aged↗
PubMed1989

The effect of argon laser trabeculoplasty upon the normal human trabecular meshwork.

The effect of argon laser trabeculoplasty (ALT) upon the normal human trabecular meshwork, as determined by scanning and transmission electron microscopy is reported. The lower nasal and temporal quadrants of an eye received ALT 5 and 1 day, respectively, prior to enucleation. Laser impact sites were identified as focal disruptions of trabeculae, together with connective tissue and cellular debris. Surviving trabecular endothelial cells near the laser lesions exhibited signs of phagocytic and migratory activity. Exogenous macrophages also contributed to the clearance of debris. Activated trabecular cells were observed leaving the meshwork by migrating over the corneal endothelium. By 5 days post-ALT increased amounts of trabeculae lacked an endothelial covering. More activated trabecular cells but fewer macrophages were noted. A laser lesion sited close to Schwalbe's line induced, within 5 days, a local corneal endothelial wave front to advance towards it, thus reflecting many late failed ALT specimens that we have seen.

Humans↗
PubMed1989

Cellular carbohydrate components in human, rabbit and rat lacrimal gland. Studies using fluorescein and peroxidase labelled lectins.

Orbital lacrimal glands from adult male and female rabbits, rats and humans were examined for the presence of intracellular receptors of four lectins: concanavalin-A agglutinin, lutus tetragonolobus agglutinin, ricinus comunis-60 agglutinin and wheat-germ agglutinin using fluorescein-conjugated lectin and peroxidase labelling methods for fluorescence and electron microscopy, respectively. Lectins were used as specific probes to detect carbohydrate moiety of the lacrimal gland. The pattern of labelling with the lectins suggests that N-acetyl-glucosamine, N-acetyl-D-galactosamine, D-galactose, D-mannose, sialic acid and L-fucose are contained in the lacrimal gland of the three species. The significance of these findings is discussed.

Adolescent↗
PubMed1989

Long-term morphologic effects of antiglaucoma drugs on the conjunctiva and Tenon's capsule in glaucomatous patients.

Conjunctival and Tenon's capsule biopsies from two patient groups were quantitatively analyzed by light microscopy. Group A consisted of 20 patients with a primary glaucoma for whom surgery was a planned primary treatment modality. Group B was comprised of 20 patients with a primary glaucoma who had received at least two types of antiglaucoma topical medication, for a minimum of 1 year (mean, 7.7 years) before surgery. All slides were examined by two masked observers. A significant increase in the number of macrophages, lymphocytes, mast cells, and fibroblasts in the conjunctiva and Tenon's capsule and a significant decrease in the number of epithelial goblet cells were seen in the group that received long-term drop therapy. These results suggest that exhaustive medical therapy, before surgery is offered, increases the number of tissue inflammatory cells. It is possible this may enhance the risk of external bleb scarring and filtration surgery failure.

Combined Modality Therapy↗