Biomedical subjects

K Heimann

Publications and source records attributed to K Heimann.

At least 145 records · Page 8Linked to original sources

PubMed1991

[Thrombospondin and its importance in proliferative retinal diseases].

Thrombospondin (TSP), a platelet-derived protein of the integrin-binding family with adhesive and mitogenic properties was localized in surgically obtained epiretinal traction membranes from patients with traumatic (7/8) and idiopathic (8/8) proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) (6/8). Using double-label immunofluorescence techniques, we demonstrated co-localization of TSP with the endothelial cell marker, von Willebrand factor, in PDR; however, only a minority of labeled macrophages showed simultaneous staining for TSP. Therefore, macrophages are probably not a major source of TSP in PVR. We demonstrated co-distribution of blood coagulation factor XIII and two of its cross-linking substrates, fibronectin and TSP, in epiretinal membranes, as well as the detection of plasmin and presumably plasmin-induced TSP breakdown products in physiologic and pathologic vitreous. These results suggest that the coagulation system has a functional role in proliferative retinal disorders and imply that the application of inhibitors of the coagulation cascade like heparin may be a potential therapeutic approach.

Antibodies, Monoclonal↗

PubMed1991

[Daunomycin and silicone oil in treatment of proliferative vitreoretinopathy].

We describe the long-term results after treatment of 68 eyes in advanced stages of proliferative vitreoretinopathy with vitrectomy, daunomycin perfusion, and silicone oil injection. Six reoperations were performed. After 18 months, 73% of the eyes showed no signs of retinal detachment and 89% had a visual acuity greater than 20/800. These results are better than those reported in previously published studies. Whether this improvement is due to the daunomycin treatment or to more aggressive surgical techniques, such as retinotomies, remains to be answered by a randomized trial.

Combined Modality Therapy↗

PubMed1991

[Analysis of the protein pattern in physiologic and pathologic vitreous bodies by electrophoresis and immunologic identification].

The protein composition of normal and pathological human vitreous was analyzed using gradient SDS-PAGE and western blot. By electroblotting and immunodetection, the presence of ten proteins was proven in the normal vitreous. The major proteins included: albumin, transferrin, alpha-1-antitrypsin, and immunoglobulin G. For the detection of a distinct protein in the vitreous, western blot analysis seems to be an appropriate method. Using densitometric analysis of silver-stained gels, we compared the protein pattern of post-mortem vitreous, surgically obtained samples (from proliferative vitreous-retinopathy, proliferative diabetic retinopathy, and macular pucker patients), and serum. The protein composition of the pathological intraocular fluid was uniform, but different from that of normal vitreous and serum. These results suggest that a breakdown of the blood-retina barrier is the main reason for the increase of soluble proteins in the vitreous cavity under pathological conditions. The methods described allow detailed analysis of the vitreous protein pattern in intraocular proliferative disorders with a small sample volume (10 microliters).

Blood-Retinal Barrier↗

PubMed1991

The significance of complement in proliferative vitreoretinopathy.

Complement is the principal effector arm of antibody-mediated allergic response and plays a central role in the pathogenesis of many immunologic disorders. The possible pathophysiologic importance of complement was examined in the development of proliferative vitreoretinopathy (PVR). Vitreous aspirates from patients with idiopathic PVR (n = 21) and traumatic PVR (n = 15) were examined for total vitreal protein (TVP) and complement components C3, C3d, C4, and C1q-fixed immunoglobulins using enzyme-linked immunosorbent assay (ELISA), sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and western blotting. The TVP, C3 components, and factor C4 were elevated significantly in diseased vitreous. The C3-TVP and C4-TVP ratios showed no difference between traumatic and idiopathic PVR. A C4 index to estimate the rate of intraocular C4 synthesis had a mean value of 3.2 (n = 15). The increased relative amount of C3d reflected complement activation in diseased vitreous. The negative values in normal human serum and plasma and in patient plasma samples (n = 15) indicated a local reaction in the eye. The authors found C1q-fixed immunoglobulin G; this may be the cause of complement activation by the classic pathway. These findings support the opinion that the cause of PVR may be based partly on an autoimmune reaction against ocular structures.

Autoimmune Diseases↗

PubMed1990

Proliferative vitreoretinopathy--is it anything more than wound healing at the wrong place?

Proliferative vitreoretinopathy (PVR) is a reactive process of the ocular tissue after perforating trauma, retinal detachment, and surgical manipulations. Although several studies, most of them experimental, have focused on the detection of specific etiologic factors in the development of PVR, there is compelling evidence that PVR is nothing more than a physiologic tissue repair process with undesirable consequences for the retina. Important features of PVR involving the role of platelets, mononuclear phagocytes, and fibroblasts parallel the chain of events observed in tissue repair elsewhere in the body. Numerous experimental models for PVR, originally designed to find specific stimuli for the generation of intraocular traction membrane formation, have shown that the process of PVR is the common pathway of the eye's reaction to vitreoretinal trauma of any kind. Accordingly, vitreoretinal surgeons could learn a lot from the work of other disciplines, e.g. surgery and dermatology, on wound healing, and the factors known to modify wound healing elsewhere in the body should be taken into consideration. The well-established impairment of tissue repair processes caused by medical treatment with corticosteroids and cytotoxic agents suggests a combined medical approach to PVR as an adjunct to surgical treatment, using refined methods of application and dosage. Steroids and cytotoxic drugs will influence the course of PVR by suppressing macrophage recruitment and the initial inflammatory reaction as well as the proliferative phase of wound healing with traction retinal detachment, respectively.

Blood Platelets↗

PubMed1990

Immunoglobulin G, complement factor C3 and lymphocytes in proliferative intraocular disorders.

This study examines a possible immunological contribution to the development of proliferative intraocular disorders (PID) with traction retinal detachment. We analysed 24 periretinal membranes and 35 vitreous aspirates from patients with idiopathic proliferative vitreoretinopathy (PVR), traumatic PVR, and proliferative diabetic retinopathy (PDR). Lymphocytes and complement factor C3 deposits could not be detected in any of the membrane specimens. IgG was present in all but one of the PVR membranes but in less than half of the PDR specimens and there to a lesser extent. The IgG immunoreactivity was not collocalized with macrophages but instead located to the extracellular matrix. The intravitreal levels of IgG (ELISA) and protein were elevated in PID but the range of these biochemical changes was so wide that there were no significant differences of the IgG levels between the single types of PID. Using electrophoresis and Western blotting, C3 was detected in normal and pathologic vitreous but smaller C3 fragments indicative of C3 breakdown were only found in PID.

Blotting, Western↗

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

[Moschcowitz syndrome and retinal neovascularization with retinal detachment].

The authors examined a patient with thrombotic thrombocytopenic purpura (Moschcowitz's disease). Six months after the patient was first seen with massive bilateral vascular occlusion, she presented with advanced retinal neovascularization in both eyes and traction retinal detachment in the left eye. While traction retinal detachment is a very rare sequela of this hematologic disorder, patients with Moschocowitz's disease should be carefully examined for early signs of ocular neovascularization in order to prevent loss of residual vision.

Adult↗

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

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

Toxicity of intraocular daunomycin.

Due to its antiproliferative properties, daunomycin is of potential use in the treatment of proliferative vitreoretinopathy and capsular fibrosis after cataract extraction. Previous biomicroscopic, electrophysiologic and histologic studies in the rabbit had shown that higher drug doses caused damage to all ocular structures after exposure to daunomycin. Based on the animal studies, we concluded that there is a small but usable therapeutic window for this drug. As electrophysiology and histology are not readily available for the examination of the human silicone-filled eye, we used clinical examination and fluorescein angiography as toxicity parameters. The comparison of the visual acuity and the central visual field showed that visual acuity is a reliable parameter of retinal and macular function after vitreoretinal surgery. Any specific toxicity attributable to daunomycin could not be observed in our patients. We conclude that the daunomycin perfusion (7.5 mg/l for 10 min.) is well tolerated by the human eye.

Daunorubicin↗

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

[Artificial iris diaphragm in silicone oil surgery].

An artificial PMMA iris diaphragm is described, which is similar to an inferior iridectomy after Ando. The diaphragm can be implanted in aniridic eyes requiring silicone oil surgery. It successfully inhibits contact between the silicone oil bubble and the corneal endothelium.

Aniridia↗