The place of trabeculectomy in the treatment of glaucoma.
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Age Factors↗
Biomedical subjects
I Grierson
Publications and source records attributed to I Grierson.
Structural basis of contraction in vitreal fibrous membranes.
A combined ultrastructural and immunofluorescent study was conducted on experimentally induced fibrous membranes in the vitreous of adult rabbits. Autochthonous tissue cultured fibroblasts were injected into the mid-vitreous of one eye of each of 25 rabbits. The animals were monitored routinely with an ophthalmoscope and slit-lamp and were killed at various time periods between 5 minutes and 6 months. Appropriate tissue was taken for light microscopy, transmission electron microscopy, scanning electron microscopy, and indirect immunofluorescence. With this model we were able to show that the contractile elements in fibrous membranes are probably modified fibroblasts called myofibroblasts which are most abundant 3 to 6 weeks after injection. This is the time when retinal detachment usually occurs. It is our impression that, as traction membranes develop, there is not so much an increase in the contractile elements of the constituent cells as a rearrangement of the existing cytoplasmic microfilaments into compact highly organised bundles called stress cables. The behaviour and ultrastructural characteristics of intravitreal fibroblasts compare with the action of fibroblasts in the healing of wounds.
Animals↗
Preliminary observations on human trabecular meshwork cells in vitro.
This report presents our preliminary observations on the trabecular meshwork from human eyes up to 5 days post-mortem in tissue culture. Satisfactory primary cultures were obtained from about 20% of the 423 explants which were investigated. The period prior to growth was from 4 days to 4 weeks and from the appearance of the initial outgrowth it took 25 to 30 days to reach maximum cellular spread within the culture chambers. The progress of the explant and the spreading of the trabecular meshwork cells was monitored by phase-contrast microscopy, time-lapse cinephotomicrography, light microscopy, transmission electron microscopy, scanning electron microscopy and autoradiography (using tritiated thymidine). On the basis of their ultrastructural appearance the cultured meshwork cells seems to be metabolically active. Their cytoplasm contained abundant rough endoplasmic reticulum, many mitochondria, a well developed Golgi apparatus and many coated and uncoated micropinosomes. However, even in short-term culture the trabecular meshwork cells had adapted to the artificial environment of our system and no longer resembled "normal" trabecular meshwork cells as seen in vivo. Since trabecular meshwork cells can quickly adapt their morphology in a culture environment and because the adult human meshwork contains a significant population of non-trabecular cells, the value of long term culture as a means of investigating the cellular activity of the normal and glaucomatous outflow system must be open to question.
Culture Techniques↗
Vitreous membrane formation after experimental vitreous haemorrhage.
The formation of vitreous membranes after intravitreal haemorrhage was studied in rabbit eyes. Early detachment of the posterior vitreous was followed by the formation of large cellular membranes, composed of aggregated giant macrophages within fine collagen sheets. Progressive reabsorption of the cellular material resulted in acellular membranes composed of endogenous vitreous collagen. Fibroblastic activity was not observed, and it was considered that the vitreous body, particularly its hyaluronic acid component, may present a barrier to the invasion of fibroblasts and other cells during the resolution of vitreous clots.
Animals↗
Contractile proteins in ocular tissues. Their role in health and disease.
Various cytoskeletal and contractile filamentous systems are located within non-muscular eukaryotic cells including microtubules, intermediate filaments, myosin filaments, and actin microfilaments. Microtubules are a major component of cilia, flagella, axons, and the mitotic spindles, but apart from these more specialized roles they are cytoskeletal structures and are involved in the directional movement of organelles within the cytoplasm. Intermediate filaments are structurally and biochemically similar to neurofilaments and although they are present in most cells they are particularly prominent in mesenchymal cells. Their function is not fully understood but they probably have a supportive role and constrain organelles including the nucleus in position within the cell. The contractile proteins, actin and myosin, in their most complex forms are found as a variety of filamentous structures which are involved in such diverse processes as motility, adhesion, phagocytosis, endocytosis, and cytokinesis. In this study the distribution of cytoskeletal an contractile elements in the non-muscular tissues of the human and the rabbit eye were investigated both in vivo and in vitro using electron microscopy and indirect immunofluorescence. Particular emphasis was placed on the role of cytoplasmic filaments in normal tissue function and their possible significance in various pathological conditions.
Actins↗
Vitreous haemorrhage and vitreal membranes.
Autogenous whole blood and fibroblasts were introduced into the vitreous of rabbits and the subsequent fate of these materials was monitored by light microscopy, transmission electron microscopy, and scanning electron microscopy. Our particular interest was the nature, formation, and development of vitreal membranes. The membranes which form after the introduction of autogenous whole blood consist of organized vitreal collagen, haematogenous debris, macrophages and, in the later stages, effete multinucleate macrophages. Fibroblastic activity and the formation of 640 A banded collagen were not found and although the membranes were persistent they did not produce retinal detachment and retinal changes were minimal. These membranes correspond to the so-called yellow ochre membranes which form in human eyes as a consequence of intravitreal bleeding. These pathological changes may be compared to those found when autogenous dermal fibroblasts are introduced into the vitreous.
Animals↗
The pathology of vitreous hemorrhage. II. Ultrastructure.
We undertook an ultrastructural study of the dual processes of hemolysis and vitreous membrane formation during the resolution of vitreous blood clots in rabbits. Red blood cell degradation began within 24 hours before the onset of the inflammatory response and occurred mainly in the extracellular matrix. Macrophage activity was directed at clearing lysed RBC debris, rather than engulfing whole RBCs. Hemolysis in the vitreous may have been initiated by the unfavorable microenvironment. Two types of vitreous membranes occurred during vitreous clot lysis. Cellular membranes were composed of aggregates of giant macrophages enclosed within a thin collagen sheet. Acellular membranes developed from coaggregated vitreous collagen fibers. A prominent acellular membrane surrounded the blood clot as a pseudocapsule. No fibroblasts or fresh collagen deposition were observed.
Animals↗
The cellular response to blood in the vitreous: an ultrastructural study.
The cellular response to whole blood injected into the vitreous cavity of rabbits was studied by transmission and scanning electron microscopy. Inflammatory cell invasion was slow to commence (2--3 days) and was predominantly mononuclear. Although firmly established by 6 days, the cell response remained low-grade with a high proportion of giant macrophages. In addition, multinuclear giant cells were observed, even as long as 18 mth after blood injection into the vitreous, and their formation appeared to result from the fusion of young cells with older macrophages. Phagocytosis of red cells by macrophages was frequently observed, but the major pathway for red cell degradation appeared to be extracellular haemolysis. In general, the cell response was similar to that in a "low-turnover" granuloma, and it is suggested that this atypical response to blood deposits may be due to the unusual nature of the connective tissue matrix of the vitreous.
Animals↗
Microfilaments in the cells of the human trabecular meshwork.
In this present study the results are presented of a combined ultrastructural and immunofluorescent investigation of 'smooth muscle' elements within the cytoplasm of human trabecular meshwork cells. The cytoplasm of human meshwork cells both in vivo and in vitro is replete with 10 nm intermediate filaments and also contains smaller 6 nm filaments which are particularly prominent in the cell processes. By immunofluorescence using sera rich in antibodies to contractile proteins, particularly actin, cultured meshwork cells showed strong cytoplasmic fluorescence. On occasion the cytoplasmic fluorescence was diffuse, but more often recognisable bundless (stress fibres) or a loose fibrillar framework was found. The possible role of structural and contractile cellular proteins in trabecular function was discussed.
Actins↗
The trabecular wall of Schlemm's canal: a study of the effects of pilocarpine by scanning electron microscopy.
The scanning electron microscope was used to study the endothelium lining the trabecular wall of Schelemm's canal in 10 human eyes enucleated in treatment of choroidal melanomas. The eyes of 5 patients had been treated before enucleated with pilocarpine drops, and the remaining 5 were untreated and served as controls. In the pilocarpine-treated tissue there was an increased prominence of cellular bulges in the endothelial monolayer, and the endothelial pores were both larger and more frequent than in the untreated eyes. By the use of Poiseuille's formula it was calculated that the resistance offered by the pore system to the drainage of aqueous in the pilocarpine-treated group was approximately one-ninth of that in the control series.
Choroid Neoplasms↗
The effects of topical pilocarpine on the morphology of the outflow apparatus of the baboon (Papio cynocephalus).
The morphology of the outflow system of the baboon (Papio cynocephalus) was studied by light microscopy and transmission electron microscopy in tissue from eyes treated with topical pilocarpine. In one group of five animals the intraocular pressure (IOP) was maintained at 18 mm /g in both the experimental and the control eye of each baboon for the duration of the experiment. The endothelial meshwork was more distended, and there was a significantly greater number of giant vacuoles in the lining endothelium of Schlemm's canal in the pilocarpine-treated eyes than in the corresponding controls. However, in another series of animals, IOP was not maintained, and the differences between the treated and untreated eyes was much less striking. There appeared to be little evidence that the increase in vacuolation was produced by the direct action of pilocarpine on the endothelium of Schlemm's canal; more likely, it was a consequence of an increased passage of fluid through the drainage system. In addition, we have been able to show that (1) the mode of primary fixation can produce partial reversal of the pilocarpine effect and (2) the mechanical manipulation which is required to determine outflow facility has a deleterious effect on the morphology of the outflow tissues.
Animals↗
A light microscopic study of the effects of testicular hyaluronidase on the outflow system of a baboon (Papio cynocephalus).
An attempt was made to investigate the effects of hyaluronidase on the morphology of the baboon outflow system. The eyes of six adult baboons provided the material for this histological study. For each animal the IOP in both eyes was maintained at 18 mm Hg, and 150 IU of testicular hyaluronidase were introduced into one eye and a control solution into the other. It was observed by light microscopy that the outer meshwork was more distended in the hyaluronidase-treated outflow system than in the corresponding controls. Further, it was found from a quantitative analysis that the incidence of giant vacuoles in the endothelium of Schlemm's canal was greater in the experimental than the control eye of each animal. The difference between the vacuole counts in the experimental and control eyes was significant in five of the six animals. These preliminary findings provide morphological evidence which indicates that there is a hyaluronidase-sensitive barrier to aqueous outflow in the baboon drainage system.
Animals↗
Associations between the cells of the walls of Schlemm's canal.
The associations between the cells of the corneoscleral and trabecular walls of Schlemm's canal from the three primate species human, baboon and rhesus monkeys were examined by transmission electron microscopy. Small gap junctions and occluding junctions modify the lateral borders between the canalicular endothelial cells. The endothelial monolayer on the corneoscleral aspect of Schlemm's canal is separated from several layers of fibrobasts by a continuous basement membrane. The fibroblasts are embedded in a dense collagenous matrix and at the regions of cellular association, modifications are restricted to simple maculae adhaerentes. The endothelial monolayer on the trabecular aspect of Schlemm's canal does not have a continuous basement membrane but maintains its association with the underlying endothelial meshwork by means of process connections. In the endothelial meshwork, the native meshwork cells link with each other by gap junctions and maculae adhaerentes.
Adolescent↗
Further observations on the process of haemophagocytosis in the human outflow system.
The outflow system was studied in seven human traumatised eyes in which there was a hyphaema (injury-enucleation periods 7h to 35 days). Extracellular lysis of red cells was present, but lysed red cells were not found in the outer part of the meshwork. Exogenous macrophages and endogenous endothelial cells contained red cells and their breakdown products and evidence was obtained to indicate intracellular haemolysis as the cells passed through the meshwork. Penetration of the lining endothelium of Schlemm's canal by red cells and macrophages was a rare observation and this was attributed to the presence of a co-existing hypotonia.
Adolescent↗
Comparative studies of erythrophagocytosis in the rabbit and human vitreous.
The ultrastructural changes which occurred during red cell degradation in the vitreous were studied in rabbit and human eyes. The major pathway for red cell lysis was extracellular in both species, and this type of haemolysis was probably induced by the unfavourable environment in the vitreous and by age changes in the red cells themselves. The released red cell debris was then phagocytosed by invading macrophages. Intracellular lysis also occurred within the cytoplasm of large macrophages after ingestion of whole red cells by the phagocytes. Thus inflammatory cells were always ultimately involved in both forms of red cell lysis in the vitreous. Intracellular lysis appeared to be more common in human cases of recurrent intravitreal haemorrhage associated with intravitreal new vessel formation. In addition, a higher proportion of young macrophages was observed in the inflammatory cell exudates of recurrent haemorrhages, suggesting that macrophage turnover was more rapid in these cases.
Adult↗
Pressure effects on flow channels in the lining endothelium of Schlemm's canal. A quantitative study by transmission electron microscopy.
A quantitative investigation, using transmission electron microscopy, was conducted to determine the relative incidence of nuclei, giant vacuoles and their pores, non-vacuolar transcellular channels and minipores in the endothelium lining the trabecular aspect of Schlemm's canal at various levels of intraocular pressure in the range 0--50 mmHg. The eyes of twelve rhesus monkeys were used and prior to intracameral fixation, the intraocular pressure was maintained at the appropriate level for one hour. The results obtained from a single section analysis showed that the incidence of giant vacuoles, vacuolar and non-vacuolar transcellular channels and minipores could be related to pressure. An analysis of serial reconstructions of samples of the vacuoles indicated that vacuolar transcellular channels became more numerous and more enlarged as pressure was increased. We concluded that the transcellular pore system serves as a major outflow route for aqueous humour.
Animals↗
Clearance of debris from the iris through the drainage angle of the rabbit's eye.
The fate of particulate material on entering the drainage angle of the rabbit's eye was investigated by transmission electron microscopy. The infiltrate was produced by photocoagulation of the iris. Initially it consisted of plasma, connective tissue and cellular debris, fibrin, and red blood cells. Later, free melanin granules, polymorphs, macrophages, and iris clump cells were all seen to enter the drainage system. Native meshwork cells were found to be active phagocytes and began to degrade various components of the infiltrate within 2 hours of the formation of the iris lesions. Corneal endothelial cells, the cells which cover the iris pillars, and the adventitial cells of the ciliary body were less active but were also phagocytic.
Animals↗