Biomedical subjects

M Weller

Publications and source records attributed to M Weller.

At least 307 records · Page 17Linked to original sources

PubMed1990

The pathogenesis of vitreoretinal proliferation and traction: a working hypothesis.

Traction retinal detachment due to proliferative vitreoretinopathy (PVR) is a serious complication of ocular trauma, retinal detachment, and previous vitreoretinal surgery. The cause is the active proliferation of fibroblasts, glial cells, and retinal pigment epithelial cells in the periretinal spaces, leading to the formation of contractile cellular membranes. The generation of growth and mitosis stimulation for these cells has remained obscure. We postulate that invading macrophages and local microglia secrete growth factors, notably PDGF (platelet-derived growth factor), which in turn mediates the mitogenic effects of transferrin (TF), a protein present in huge amounts in native vitreous, in plasma and in intraocular proliferative tissue.

Eye Diseases↗

PubMed1990

[Mononuclear phagocytes and their growth factors: pacemakers of proliferative vitreoretinopathy?].

Recent studies on the natural course of proliferative vitreoretinopathy (PVR) have focused on the mononuclear phagocyte system (MPS). Although the precise origin of these cells is not known, current evidence indicates that peripheral blood monocytes infiltrate a lesion initially, subsequently giving way to resident phagocytic cells. In this context the authors try to clarify some aspects of the confusing nomenclature of phagocytic monocytes, macrophages, and microglia. The concept of the blood-retinal barrier (BRB) and its breakdown in PVR are presented and discussed. Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), both secretory products of macrophages, have recently been implicated in the development of vitreoretinal pathology. These studies, however, are difficult to evaluate because the biological effects of different growth factors are closely interrelated and vary widely, including both inhibition as well as stimulation of cell growth. The authors hypothesize that plasma of macrophage-derived TGF-beta provokes an increase in fibronectin synthesis, which in turn is responsible for the fibrotic rebuilding of the vitreoretinal interface in PVR. As an adjunct to the pharmacological treatment of PVR with Daunomycin the use of steroids is recommended to suppress the initial macrophage activation and related dysfunction of the BRB.

Animals↗

PubMed1990

[Proliferative vitreoretinopathy: new discoveries in pathophysiology and therapy].

In this article the authors review present knowledge concerning the pathogenesis of proliferative vitreoretinopathy (PVR). The function of cells such as macrophages, fibroblasts, retinal pigment epithelial cells, and glial cells, as well as their interaction with constituents of the extracellular matrix such as fibronectin, vitronectin, and factor XIII, are described. Current data on growth factor involvement in the pathogenesis of PVR are explained. Attention is focused on the histopathological differences between traumatic and idiopathic membranes, "young" and "old" membranes, and PVR and diabetic membranes. On the basis of the findings presented, the importance of the breakdown of the blood-retinal barrier, the participation of the coagulation system, and immunological aspects of membrane formation are discussed. Conceivable new strategies for medical treatment of PVR are proposed.

Blood-Retinal Barrier↗

PubMed1990

Increased intrathecal synthesis of fibronectin in bacterial and carcinomatous meningitis.

Immunoreactive fibronectin (Fn) was quantified in paired cerebrospinal fluid (CSF) and serum samples from patients with bacterial meningitis (n = 46), tick-borne encephalitis (TBE) (n = 6), HIV infection (n = 6), Guillain-Barré syndrome (n = 5), carcinomatous meningitis (n = 11), multiple sclerosis (n = 15), disk disease (n = 11), and controls (n = 28). A highly significant elevation of CSF Fn was found in bacterial meningitis, TBE, and carcinomatous meningitis. There were no significant differences in serum Fn between any of the groups. An Fn index to estimate the rate of intrathecal Fn synthesis reached the highest value in bacterial meningitis. Our findings suggest that CSF Fn may be an indicator of adequate host reaction and tissue repair. For diagnostic purposes, the determination of CSF Fn probably does not add much to routine CSF laboratory tests.

Albumins↗

PubMed1990

Blood coagulation factor XIII contributes to the development of traction retinal detachment.

The blood coagulation factor XIII catalyzes the crosslinking of fibrin monomers at the end of the coagulation cascade. Additional functions are the enzymatic coupling of fibrinectin to itself, fibrin, and collagen. We located the two subunits of factor XIII in 20 surgically obtained periretinal membranes, using double label immunofluorescence microscopy. Both subunits of factor XIII could be detected in all specimens. The positive staining in all specimens examined prompted us to determine the source of factor XIII. The abundant fibroblastic cells did not contain factor XIII. Macrophages, half of which stained for the alpha-subunit of factor XIII could not account for the presence of factor XIII because these cells were not present in all specimens, and did not stain for the beta-subunit. Factor XIII is probably derived from the exudation of plasma and platelets through disrupted blood-ocular barriers. This is confirmed by the detection of both subunits in vitreous aspirates from patients with proliferative intraocular disorders (n = 15) by Western blotting.

Antibodies, Monoclonal↗

PubMed1990

Iron-binding proteins in the human vitreous: lactoferrin and transferrin in health and in proliferative intraocular disorders.

Transferrin, recently detected in preretinal membranes, may contribute to cell proliferation by iron donation for mitosis. We have investigated whether lactoferrin, the second iron-binding protein of the human vitreous, could play a similar role in proliferative intraocular disorders (PID). Using immunochemistry, however, we could not label lactoferrin in surgically obtained membrane specimens from patients with idiopathic proliferative vitreoretinopathy (PVR), traumatic PVR, and proliferative diabetic retinopathy (n = 15). The amounts of both proteins in normal human vitreous, as measured by enzyme-linked immunosorbent assay, were 73.7 +/- 6.6 mg/l for transferrin but below 50 micrograms/l for lactoferrin. Transferrin was also determined in 35 vitreous aspirates from patients with PID. The highest levels were found in idiopathic PVR (846 +/- 256 mg/l), followed by proliferative diabetic retinopathy (405 +/- 121) and traumatic PVR (197 +/- 83 mg/l). A statistically significant difference between the three types of PID and physiologic vitreous, respectively, was not observed. The total vitreal protein, however, was significantly elevated in all three groups of PID.

Cell Membrane↗

PubMed1990

[Vitronectin: mediator of cell adhesion in proliferative vitreoretinopathy?].

Vitronectin, also known as protein S, the "serum spreading factor", or epibolin, was detected as an essential mediator of adhesion and spreading in many cells in vitro. The relatively low molecular weight of 65 kDa and a high plasma level of 200 mg/l implicate vitronectin as a possibly important factor in the pathogenesis of proliferative vitreoretinopathy (PVR) which is characterized by a breakdown of blood-ocular barriers. In a study of 15 periretinal membranes, using double label immunofluorescence techniques, we found vitronectin to be a significant component of the specimens' extracellular matrix in 13 cases. Vitronectin is co-localized with fibronectin, a much larger glycoprotein suggested as being involved in the pathogenesis of PVR. Among the biological properties of fibronectin are a role in cellular migration, adhesion, and proliferation. Both proteins share a unique cell recognition amino acid sequence, which mediates the receptor-dependent interaction between the extracellular matrix macromolecules and proliferating cells. Plasma is suggested as the major source of vitronectin in PVR because vitronectin could be detected in vitreous aspirates from patients with PVR, using electrophoresis and immunoblotting, but not in physiological human vitreous.

Cell Adhesion↗

PubMed1990

[Vitronectin and fibronectin receptors in proliferative retinal diseases].

Integrins are membrane receptors which, together with their corresponding adhesion proteins, constitute a versatile recognition system and provide cells with information for position, anchorage, differentiation, migration, and growth. Vitronectin and fibronectin are two potent mediators of cell adhesion which, together with their receptors, represent a highly sophisticated system of communication in proliferative intraocular disorders. Using an immunofluorescence technique, we demonstrate a similar pattern of partial colocalization of vitronectin and fibronectin in proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). Furthermore, we show the expression of the corresponding cell surface receptors for vitronectin and fibronectin in membranes from patients with traumatic PVR (n = 8), idiopathic PVR (n = 8), and PDR (n = 6). At this time, it seems that further studies on integrins and their significance in proliferative retinal disorders are necessary before pharmacological approaches based on receptor antagonism can prove themselves to be possible and clinically applicable.

Fibronectins↗

PubMed1990

Giant preretinal membrane formation behind a silicone oil bubble in a hypotensive eye.

A patient who suffered a severe contusion injury with scleral rupture and subsequent peracute development of proliferative vitreoretinopathy was referred after wound closure at the local ophthalmology center. Initial treatment of the almost blind eye consisted of vitrectomy, silicone oil tamponade, and intraocular daunorubicin. A vitreous aspirate obtained during surgery was analyzed biochemically by electrophoresis and Western blotting. After a few days, the patient needed further surgical intervention because silicone oil was leaking through the primary sutured scleral wound. A giant fibrinous membrane extending over the posterior pole was removed. Double-label immunofluorescence examination of this specimen showed a positive reaction for transferrin, the cell surface transferrin receptor, fibrinogen, fibronectin, macrophages, and vimentin. No staining was obtained for proliferating cell antigen and T-lymphocyte antigen. The analysis of this case with a very well-defined clinical course offers valuable insight into the early stages of proliferative vitreoretinopathy.

Electrophoresis, Polyacrylamide Gel↗

PubMed1990

[Detection of coagulation factor XIII in the vitreous body and periretinal membranes in proliferative retinal diseases].

The human blood coagulation factor catalyses the cross-linking of fibrin monomers at the end of the coagulation cascade. Additional functions are the coupling of fibronectin and collagen to each other and fibrin. Therefore we tried to investigate the significance of factor XIII in the development of intraocular membranes. Using gel electrophoresis and western blotting, both subunits (A and B) of factor XIII could be detected in vitreous aspirates from patients with "idiopathic" proliferative vitreoretinopathy (PVR) (n = 5), traumatic PVR (n = 5), and proliferative diabetic retinopathy (n = 5). In contrast the vitreous of five human "normal" post mortem eyes did not contain the subunits of factor XIII. Furthermore, we observed immunofluorescence staining for both subunits of factor XIII in 20 surgically obtained periretinal membranes. In early cellular as opposed to late hypocellular membranes we observed stronger labeling for both subunits of factor XIII. With double label staining techniques, the fibroblastic cells recognized by vimentin staining did not contain factor XIII. About 50% of the macrophages stained positive for the A-subunit of factor XIII. We observed no labeling for the B-subunit in macrophages. Therefore, we hypothesize that factor XIII in proliferative vitreoretinal disorders (PVR, PDR) is derived from the exudation of plasma and platelets through disrupted blood-retinal barriers.

Diabetic Retinopathy↗

PubMed1990

[Lactoferrin and transferrin--iron-binding proteins in physiological and pathological vitreous bodies].

Having demonstrated transferrin (TF) and the TF receptor in periretinal membranes, we now present results of quantitative studies of TF and lactoferrin (LF), another protein with iron-binding properties. Normal human vitreous contains 74 +/- 7 mg/l TF, but less than 50 micrograms/l LF (ELISA). The TF levels determined in vitreous aspirates from patients with proliferative intraocular diseases [traumatic proliferative vitreoretinopathy (PVR), idiopathic PVR, and proliferative diabetic retinopathy (PDR)] were higher. A statistically significant difference between the levels in the vitreous in the three types of proliferative intraocular disease and in physiological vitreous was not observed. In contrary to TF, LF could not be labeled in surgically obtained membrane specimens using immunochemistry. Apparently LF does not have the same importance for cell proliferation in proliferative intraocular diseases as is suggested for TF.

Enzyme-Linked Immunosorbent Assay↗

PubMed1990

[Quantitative determination of 5 vitreal proteins in the normal vitreous body and proliferative retinal diseases].

While progress in vitreoretinal surgery has been very rapid in recent years, our understanding of the biochemistry of normal and pathological vitreous is still limited. Therefore, we developed non-competitive ELISA techniques for the quantification of five vitreal proteins which, together with vitreal collagen (300 mg/l), account for more than 70% of the total vitreal protein. Physiological levels of the individual proteins were determined as follows: albumin 293 +/- 18 mg/l, IgG 34 +/- 3 mg/l, transferrin 74 +/- 7 mg/l, alpha 1-antitrypsin 14 +/- 3 mg/l, alpha 1-acid glycoprotein 4 +/- 0.7 mg/l. Mean values for these proteins were also obtained in vitreous aspirates from patients with traumatic proliferative vitreoretinopathy (PVR) (n = 10), idiopathic PVR (n = 10) and proliferative diabetic retinopathy (PDR) (n = 15). Significant differences were found for total vitreal protein and alpha 1-antitrypsin between the control groups and the three vitreoretinal disorders, between the PDR and control group for transferrin, and between both types of PVR and controls for alpha 1-acid glycoprotein. Given the high plasma levels of the individual proteins quantified in this study and the uniform rise in total vitreal protein, a disturbancee of blood-retinal and blood-vitreal barriers seems to be an essential features of proliferative intraocular disorders. No disease-specific change in the protein pattern could be detected for the three disorders examined.

Blood Proteins↗

PubMed1989

Hysterical symptoms in ophthalmology.

Ophthalmologic symptoms are often not sufficiently accounted for by organic pathology. The complaints of these patients have been labeled hysterical, psychogenic, non-organic, or functional. The psychiatric nosology in this area may be the most confusing in the whole field of clinical medicine. The Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) offers a classification designed to reduce non-empirical concepts and ideology to a minimum. On this background, we discuss the hysterical symptoms encountered in clinical ophthalmology with special emphasis on psychogenic amblyopia and blepharospasm. Motor symptoms are commonly not of psychogenic origin. It is suggested that ophthalmologists are most likely to treat patients with psychogenic symptoms, using suggestion, patience, and reassurance. Few patients require psychiatric consultation and a specific psychiatric therapy. The association of hysteria with organic brain disease and the issue of symptom lateralization are briefly discussed. Eventually, we reject the psychoanalytic approach and suggest that the concept of abnormal illness behavior and the neurobiological models involving corticofugal inhibition, primitive reflex mechanisms, and an attention disturbance, serve best to understand the nature of the phenomenon hysteria.

Amblyopia↗

PubMed1989

Visual hallucinations. An outline of etiological and pathogenetic concepts.

Visual hallucinations have played an important role in religion, culture, and all concepts of mental disease. A brief review of these phenomena in healthy individuals as well as in clinical medicine is provided. We analyse the pathomechanisms involved in the development of visual hallucinatory experiences and argue that no single model can serve to explain all the phenomena encountered in the field of visual hallucinations. We question the validity of the current distinction between hallucination and illusion, and delineate conditions which are only appreciable psychologically, e.g. the 'imaginary playmates' of childhood and visual hallucinations in the face of a severe grief reaction. At least three putative mechanisms for the genesis of visual hallucinations can be described in biological terminology: irritative phenomena, release phenomena, and processing disturbances within the visual pathways.

Brain Diseases↗

PubMed1989

Transferrin and transferrin receptor expression in intraocular proliferative disease. APAAP-immunolabeling of retinal membranes and ELISA for vitreal transferrin.

Transferrin (TF) is the major transport protein involved in human iron metabolism. The expression of the cell-surface TF receptor is associated with cellular proliferation, the dominant feature of proliferative vitreoretinal disorders with traction retinal detachment. A total of 14 retinal membranes from patients with different clinical diagnoses contained immunoreactive TF. Expression of the cell-surface TF receptor was confirmed by a monoclonal anti-human TF-receptor antibody label in 11 of the 14 specimens. We developed a noncompetitive enzyme-linked immunosorbent assay (ELISA) for TF and found it to be a significant component of vitreal protein, with a level of 65.7 +/- 33.9 mg/l. Vitreal TF as a major iron acceptor probably has a protective function, but its interaction with macrophages and its growth-promoting activity may subsequently stimulate the proliferation of fibroblasts and retinal pigment epithelial cells.

Antibodies, Monoclonal↗

PubMed1989

[Immunohistology of proliferative vitreoretinopathy following giant tear detachment].

A patient with multiple bilateral retinal holes and a history of several prior surgical interventions was treated by pars plana vitrectomy for total traction retinal detachment in the right eye. The preretinal membrane specimen obtained surgically was analyzed using an immunological label for macrophages, vimentin, cytokeratin, fibronectin, fibrinogen, transferrin, the transferrin receptor, blood coagulation factor XIII-A and XIII-S, and haptoglobin. The results of the study suggest that factor XIII and fibronectin play an important role in idiopathic PVR. Proliferating cells of fibroblastic appearance invade a preretinal exudate and restructure the injured vitreoretinal tissue, forming a contracted scar. Macrophages, known to be characteristic of early posttraumatic PVR development, were not present in this case of PVR, where traction retinal detachment was presumably induced by the formation of multiple retinal holes.

Eye Proteins↗

PubMed1989

[Immunohistochemical findings in proliferative retinal diseases--on the significance of fibronectin, macrophages and transferrin].

Surgically excised vitreoretinal membranes of different etiology were analyzed immunochemically using the APAAP stain. We investigated the presence of macrophages, lymphocytes, proliferating cell antigen, fibronectin, vimentin, cytokeratin, transferrin (TF), and the TF receptor. Fibronectin and vimentin were observed both in idiopathic and traumatic proliferative vitreoretinopathy (PVR); however, abundant macrophages were a typical feature only of traumatic PVR. A Coats' disease specimen contained fibronectin, vimentin, TF, and macrophages. Staining for proliferating cell antigen, lymphocytes, and cytokeratin was negative in all specimens. TF was detected in all membranes, and it was possible to label the receptor in 11 of 14 patients. TF quantities in native human vitreous were measured to be 65.7 mg/l by ELISA. TF is an essential growth factor for cultured cells, and current evidence suggests that TF may be involved in the pathogenesis of proliferative intraocular disease.

Cicatrix↗

PubMed1989

Immunochemical analysis of periretinal membranes. Review and outlook.

The progressive immobilization of retinal detachment through periretinal membrane formation is a major cause of blindness and difficult to treat. Initial morphological studies have revealed several features of the natural history, but immunochemistry yielded the most important results. Among the antigens detected in periretinal membranes are GFAP, keratin, vimentin, actin, fibronectin, collagen, and macrophage antigen. Immunochemical findings, however, have to be carefully interpreted and several pitfalls have to be avoided. The significance of new interesting factors in proliferative intraocular disease, e.g. platelet-derived growth factor, transforming growth factor-beta, or the recently described integrins, is most likely to be determined by detailed immunochemical studies on surgically obtained human specimens.

Actins↗