Biomedical subjects

K Heimann

Publications and source records attributed to K Heimann.

At least 73 records · Page 4Linked to original sources

PubMed1998

Failure of sorivudine therapy in progressive outer retinal necrosis caused by varicella zoster virus.

BACKGROUND: We report on the case of a 23-year-old female who presented with ocular signs of progressive outer retinal necrosis (PORN) syndrome and who failed to respond to acyclovir, ganciclovir, foscarnet and oral sorivudine. METHODS: The patient was treated with the antiviral drugs acyclovir, ganciclovir, foscarnet and oral sorivudine. RESULTS: The patient failed to respond to a combination of antiviral drugs. Unfortunately, progression of the retintis occurred, which led to blindness. CONCLUSION: Despite new drugs, the prognosis of PORN is poor and recurrence is common.

AIDS-Related Opportunistic Infections↗

PubMed1998

Intravitreal daunomycin induces multidrug resistance in proliferative vitreoretinopathy.

PURPOSE: Adjuvant intravitreal daunomycin is frequently used for the management of proliferative vitreoretinopathy (PVR). In this study the authors examined whether daunomycin could induce multidrug resistance (MDR), mediated by the mdr-1 gene product P-glycoprotein, in the cells responsible for reproliferation in vivo and in human retinal pigment epithelial (RPE) cells in vitro. METHODS: Expression of P-glycoprotein was examined by immunohistochemistry in surgically removed epiretinal membranes. The cellular source of P-glycoprotein was examined by colabeling for cytokeratin, glial fibrillary acidic protein, and the macrophage marker EBM-11. P-glycoprotein expression by cultured RPE cells was assessed by reverse transcription-polymerase chain reaction and immunoblot analysis. Daunomycin toxicity was quantified by crystal violet assay. RESULTS: P-glycoprotein expression was detected in 10 of 10 patients pre-exposed to intravitreal daunomycin. In contrast, epiretinal membranes from only 2 of 13 patients never exposed to daunomycin showed faint P-glycoprotein expression. P-glycoprotein expression was strong within 8 months after daunomycin treatment and faded thereafter. Colocalization studies demonstrated predominant expression of P-glycoprotein by RPE cells. Pre-exposure of cultured human RPE cells to subtoxic concentrations of daunomycin induced resistance to daunomycin that was sensitive to the MDR inhibitor, verapamil. Induction of the MDR phenotype in RPE cells by daunomycin was associated with a minor increase in the mdr-1 mRNA level but a prominent increase in P-glycoprotein expression, thus suggesting a primarily translational mechanism of MDR development in human RPE cells. CONCLUSIONS: Intravitreal daunomycin induced P-glycoprotein expression in PVR. Reproliferation in daunomycin-pretreated patients probably necessitates cotreatment with daunomycin and inhibitors of multidrug resistance such as verapamil or administration of antiproliferative drugs such as 5-fluorouracil, which act in a MDR-independent fashion.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Capillaries are present in Bruch's membrane at the ora serrata in the human eye.

PURPOSE: Because earlier studies indicate that the choroid close to the ora serrata may have unique anatomic features such as wandering cells, blood vessels in Bruch's membrane, and accumulated pigment in the retinal pigment epithelium (RPE), the morphology of the normal human eye at the ora serrata region was investigated. METHODS: Specimens from the ora serrata region of two normal human eyes (male donors, 48 and 52 years old) were investigated by light and electron microscope. Specimens from all quadrants were studied in one eye. RESULTS: The elastic layer of Bruch's membrane extended as far as 15 microm into the peripheral choroid; capillaries were included between the elastin layer and the RPE. Nasally, from the anterior end to 2 mm posterior of the ora serrata, the RPE cells contained more melanin than did those in the adjacent posterior region. Melanin granules in the RPE cells close to the ora either formed large clusters or appeared unusually small because of fragmentation. A unique, fine lamellar, membranous material with a fingerprint-like structure was found between the basal folds of the RPE. This material is also found within the extracellular matrix of the choroid and in association with red blood cells. CONCLUSIONS: The morphology of Bruch's membrane is varied near the ora serrata because capillaries and wandering cells are present in its outer collagenous layer. Unique, fine lamellar, fingerprint-like structures are extruded from the RPE and are removed from the eye together with red blood cells. Capillaries within the inner collagenous region of Bruch's membrane at the ora serrata may not necessarily represent a pathologic response but may be a normal characteristic of thick regions of Bruch's membrane.

Bruch Membrane↗

PubMed1997

Iris pigment epithelial cells of long evans rats demonstrate phagocytic activity.

The phagocytic activities of iris pigment epithelial (IPE) cells and retinal pigment epithelial (RPE) cells of Long Evans rats towards latex beads and rod outer segments (ROS) were compared in vitro. IPE and RPE cells of Long Evans rats were isolated and pure cultures obtained. The cultures were incubated with latex beads, fixed, and analysed computer morphometrically, IPE and RPE cell cultures were also incubated with isolated ROS and examined using transmission electron microscopy. IPE cells were able to ingest latex beads. There was no significant difference between the number of latex particles phagocytized by IPE and RPE cells. After incubation with isolated ROS, IPE cells also recognized and ingested the ROS particles. However, the specific phagocytic capacity of IPE cells was 76% of that of RPE cells. The autologous IPE cells might have the potential to be used as an alternative to RPE cells for transplantation in the subretinal space.

Animals↗

PubMed1997

Porcine iris pigment epithelial cells can take up retinal outer segments.

This study investigates the ability of iris epithelial cells (IPE) to ingest rod outer segments (ROS) and compares the amount of phagocytosis of porcine RPE and IPE cells by the use of a pH sensitive fluorescent dye (carboxy SNAFL) at the light microscopic level. The dye allowed investigation of ingestion separately from binding of rod outer segments. In a second set of experiments, after exposing ferritin-labeled ROS to the cultured cells, phagosomes were also counted in electron microscopic sections. Additionally immunocytochemical staining was performed with IPE and RPE cells. Both cell types stained positive with polyclonal NaK-ATPase antibodies against the alpha 1 subunit from rat brain and kidney. The epithelial nature of the cultured cells was determined by monoclonal anti-human-cytokeratin antibodies. Moreover, the ultrastructure of the cells revealed high amounts of phagosomes smaller than 1 micron in diameter present in both RPE and IPE cells. The iron label of the phagosomes was determined by EELS spectra taken from individual phagosomes. Electron and light microscopic quantification shows that cultured IPE cells have 64% of the phagocytic capacity of the RPE with respect to phagosomes larger than 1 micron in diameter.

Animals↗

PubMed1997

Apoptosis in proliferative vitreoretinal disorders: possible involvement of TGF-beta-induced RPE cell apoptosis.

The targeted induction of apoptosis is a novel therapeutic approach to control the unlimited growth of proliferating cells. Since massive proliferation of cells at the vitreoretinal interface is a key feature of proliferative vitreoretinal disorders, we sought to identify apoptosis in epiretinal membranes from patients with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR) and macular pucker. Further, we evaluated the possible induction of apoptosis of retinal pigment epithelial (RPE) cells by transforming growth factor-beta(TGF-beta). Apoptotic cells were identified by in situ DNA end labeling and acridine orange staining on paraffin-embedded tissue sections from epiretinal membranes of patients with all vitreoretinal disorders examined. Labeled nuclei or condensed chromatin were scattered throughout the membranes or occurred in clusters. Most apoptotic cells were RPE-derived, as assessed by cytokeratin immunochemistry. No apoptotic glial cells were detected. In PVR, proliferative activity, as confirmed by Ki-67 immunochemistry, was associated with short history and rapid disease progression. Apoptotic nuclei were observed more frequently in long-standing PVR or slow progression towards traction retinal detachment. TGF-beta was detected in all control vitreous samples by bioassay at concentrations below 20 ng ml-1. TGF-beta levels increased up to 20-fold in pathological vitreous. Marked heterogeneity was observed in all patient groups. The degree of TGF-beta activation was significantly higher in PVR than in PDR. Proapoptotic effects of TGF-beta were demonstrated in cultured human RPE cells by electron microscopy, in situ DNA end labeling, comet assay and a photometric enzyme immunoassay for histone-associated DNA fragments. Apoptosis appears to be a key regulatory mechanism of growth control of specific cell populations in proliferative vitreoretinal disorders. Administration of proapoptotic growth factors such as TGF-beta may provide a novel approach to inhibit cellular proliferation at the vitreoretinal interface.

Apoptosis↗

PubMed1997

Flecked chorioretinopathy associated with Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé's syndrome is a rare skin disease characterized by multiple trichofibromas of the skin and polyps of the intestine. Ophthalmologic manifestations associated with the syndrome have not been reported in detail. CASE REPORTS AND METHODS: Two siblings suffering from Birt-Hogg-Dubé syndrome were examined clinically. Electrooculography and electroretinography were performed according to international standards. Color fundus photographs were taken as well as fluorescein angiograms. The two patients showed multiple perifollicular fibromas and trichodiscomas of the skin of the head. Funduscopy and fluorescein angiography revealed a flecked chorioretinopathy in one patient with progressive constriction of visual fields and severely reduced electroretinographic responses. Ophthalmoscopy in his sister showed peripheral pigmentary changes with only minor functional abnormalities. CONCLUSION: These findings suggest that Birt-Hogg-Dubé syndrome may be associated with a progressive flecked chorioretinopathy with constricted visual fields and that patients with the syndrome should undergo ophthalmological examination.

Aged↗

PubMed1997

Cytochemical localization of guanylate cyclase in photoreceptor cells of the mouse.

BACKGROUND: Light-stimulated excitation causes a decrease of the cGMP concentration in vertebrate photoreceptor cells. The cGMP content is restored by the catalytic action of a guanylate cyclase (EC 4.6.1.2). METHODS: The spatial distribution of guanylate cyclase was determined cytochemically in rod visual cells of the mouse. RESULTS: In retinal tissue of the mouse guanylate cyclase was found throughout the photoreceptor cells, in the outer and the inner segments, and was especially prominent in the cilia and in elongations of cilia extending into the outer segments. A reaction product of adenylate cyclase (EC 4.6.1.1) could not be demonstrated in vertebrate rod outer segments. CONCLUSION: The relatively high amount of guanylate cyclase in the inner segments and the cilia may contribute-at least in part-to the actual concentration and the time course of concentration changes of the cGMP concentration in rod outer segments.

Adenylyl Imidodiphosphate↗

PubMed1997

Iris pigment epithelium transplantation.

BACKGROUND: Iris pigment epithelium (IPE) cells and retinal pigment epithelium (RPE) cells possess the same embryonic origin. It is also known that the pigmented epithelial cells in the eye have a high transdifferentiation potential. In this study we transplanted IPE cells into the subretinal space of albino Royal College of Surgeons (RCS) rats and evaluated their influence on the degeneration of the photoreceptors. METHODS: IPE cells of Long Evans rats were isolated and pure cultures were obtained. The isolated cells were transplanted into the subretinal space of RCS rats. Light microscopic and morphometric analysis were carried out. RESULTS: The IPE transplants survived in the subretinal space and attached themselves to the Bruch's membrane. The transplanted cells were able to delay the degeneration of the photoreceptors for up to 3 months. CONCLUSION: These results suggest that IPE cells could be successfully transplanted and survive in the subretinal space. In the transplanted eyes the photoreceptors were preserved for a period of 3 months. Further studies are needed to explore the capability of IPE cells to assume the main functions of RPE cells in the subretinal space and their potential in the therapy of selective degenerative diseases of the retina.

Animals↗

PubMed1997

Comparison of tight junction permeability for albumin in iris pigment epithelium and retinal pigment epithelium in vitro.

BACKGROUND: The degenerative retinal diseases are one of the major causes of visual loss in the western world. Although heterologous RPE transplants rescue the photoreceptors in the dystrophic rat model, rejection remains a major limiting factor. Given the common embryonic origin, iris pigment epithelial (IPE) cells might be able to take over the functions of retinal pigment epithelial (RPE) cells, serving as an autologous graft for transplantation and thereby preventing rejection. One of the main functions of RPE cells is the generation of tight junctions which form the outer blood-retinal barrier. In this study we compared the tight junction permeabilities of IPE and RPE cells isolated from Long Evans rats by measuring their albumin clearances. METHODS: IPE and RPE cells were cultured on semipermeable filter supports with and without the addition of 0.02% ethylenediaminetetraacetic acid (EDTA). At selected intervals, the albumin clearances of the IPE and RPE cells were measured spectrophotometrically and compared. The morphology of the cells was compared using electron microscopy and fluorescent labeling. RESULTS: IPE and RPE cells both restricted the passage of albumin in vitro. After the modulation of tight junctions with 0.02% EDTA, the clearance increased in both types of cells in a similar fashion. The morphology of tight junctions was visualized with electron microscopy. CONCLUSION: These results indicate that the functional barrier for macromolecules is similar in IPE and RPE cells in vitro. This raises the possibility that IPE cells would form tight junctions in the subretinal space, thereby substituting for the blood-retinal barrier normally formed by RPE cells.

Actins↗

PubMed1997

Substratum adhesion and gliding in a diatom are mediated by extracellular proteoglycans.

Diatoms are unicellular microalgae encased in a siliceous cell wall, or frustule. Pennate diatoms, which possess bilateral symmetry, attach to the substratum at a slit in the frustule called the raphe. These diatoms not only adhere, but glide across surfaces whilst maintaining their attachment, secreting a sticky mucilage that forms a trail behind the gliding cells. We have raised monoclonal antibodies to the major cell surface proteoglycans of the marine raphid diatom Stauroneis decipiens Hustedt. The antibody StF.H4 binds to the cell surface, in the raphe and to adhesive trails and inhibits the ability of living diatoms to adhere to the substratum and to glide. Moreover, StF.H4 binds to a periodate-insensitive epitope on four frustule-associated proteoglycans (relative molecular masses 87, 112, and > 200 kDa). Another monoclonal antibody, StF.D5, binds to a carbohydrate epitope on the same set of proteoglycans, although the antibody binds only to the outer surface of the frustule and does not inhibit cell motility and adhesion.

Animals↗

PubMed1997

Branch retinal artery occlusion by diathermy of a persistent hyaloid artery.

PURPOSE: To report branch retinal artery occlusion caused by diathermy of a persistent hyaloid artery. METHODS: Case report. A 21-year-old woman with unilateral tractional retinal detachment caused by contraction of the persistent primary vitreous underwent vitrectomy with endocoagulation of the primary hyaloid artery. RESULTS: Postoperatively, the patient had opacification of the neurosensory retina in the area of the inferotemporal branch retinal artery accompanied by a corresponding visual field defect. CONCLUSIONS: Diathermy of a persistent hyaloid artery may be complicated by the occlusion of a branch retinal artery. In similar cases, atypical branches of retinal arteries must be considered. Dissection of the anomaly from the posterior lens capsule should be performed without coagulation or perhaps endoscopically if visualization is obscured by a Mittendorf dot.

Adult↗

PubMed1997

[Vitrectomy in treatment of eyes with complicated uveitis].

BACKGROUND: Vitrectomy serves as an important treatment modality in uveitis, removing inflamed vitreous body and eliminating secondary complications. The aim of our retrospective study was to evaluate the value of vitrectomy in the treatment of complications in uveitis. PATIENTS AND METHOD: We included 50 eyes of 50 patients suffering from chronic uveitis, which underwent vitrectomy surgery during the period of 1990 to 1993. The study only included patients who had vitrectomy for uveitis for the first time. Indications leading to surgery were density of optic media, retinal detachment, cyclitic or preretinal membranes. The mean follow-up was 455 (range 48-1420) days. RESULTS: Vitrectomy was performed at a mean delay of 452 days after initial presentation. The mean visual acuity at the time of surgery was 0.05. The best visual acuity postoperatively was measured at a mean time of 118 days after vitrectomy. Overall, at the last control, eyes with preoperative retinal detachment presented a much worse final functional result (visual acuity of 0.02) than eyes without detachment (visual acuity of 0.5). Ten eyes resulted in hypotonia after surgery (7 eyes with persisting hypotonia). Most frequent complications in the postoperative course were macular pucker (11 eyes), secondary glaucoma (10 eyes), macular edema (6 eyes) and retinal detachment (6 eyes). Fifty percent of all complications occurred within the first 3 months following surgery. CONCLUSION: Vitrectomy leads to a permanent increase in visual acuity through the treatment of complications, on the condition that a stable retinal situation was present preoperatively.

Adult↗

PubMed1997

Descemet's membrane as membranous support in RPE/IPE transplantation.

PURPOSE: The correct orientation of retinal pigment epithelium (RPE) cells is necessary for the integrity and proper function of the retina. For transplantation of RPE/iris pigment epithelium (IPE) grafts to the subretinal space in age-related macular degeneration, this cellular orientation is most effectively provided by a membranous support. The goal of this study was to establish an autologous or homologous membrane as a substratum for the growth of RPE/IPE. METHODS: Porcine and bovine RPE and IPE were placed in primary culture on a dissected sheet (5 x 5 mm) of autologous porcine and bovine Descemet's membrane in slide chambers and grown to confluence. RESULTS: RPE and IPE cells cultured on Descemet's membrane form an intact monolayer. Light and electron microscopy showed the formation of both an intact monolayer and microvilli in both cell types. CONCLUSION: Since the slow host-graft rejection appears to play an important role in the failure of RPE transplantation in the subretinal space, it is critical to be able to transplant autologous materials. The techniques presented here establish a novel means to culture RPE or IPE cells on autologous Descemet's membrane where they form a "cell monolayer patch," consisting of a fragment of Descemet's membrane with cultured RPE or IPE, which can be easily manipulated and transplanted, using an established glass pipette method.

Animals↗

PubMed1997

The artificial iris diaphragm for vitreoretinal silicone oil surgery.

BACKGROUND: Silicone keratopathy frequently develops as a complication of silicone oil tamponade in the management of severe trauma in eyes with partial or complete aniridia. We therefore designed an "open" artificial iris diaphragm to prevent silicone oil-endothelial contact. In hypotony, where insufficient circulation of aqueous allows silicone in the anterior chamber despite an open diaphragm, a new solution became necessary. The "closed" artificial diaphragm was developed. METHODS: In this retrospective study, two consecutive series of artificial iris diaphragms were compared. Forty-four patients received either an open type (20 eyes) or a closed type (24 eyes) and were observed for 409 +/- 421 days (range, 32-1912). All eyes were aphakic, normotonous, and had a traumatic, compromised iris diaphragm or were aphakic and hypotonic as a result of injury, proliferative vitreoretinopathy, proliferative diabetic retinopathy, or uveitis, with an intact natural iris diaphragm. RESULTS: Silicone oil was retained behind the open diaphragm throughout the observation period in 40% of the eyes. Major long-term complications were hypotony and fibrous overgrowth. Silicone was retained behind the closed diaphragm in 50% of the eyes. CONCLUSION: Because proliferative vitreoretinopathy is active for months and multiple surgical interventions become necessary to avoid phthisis in eyes with highly pathologic changes, longstanding or permanent silicone tamponade is used. The artificial diaphragm prevents silicone-corneal contact in approximately 50% of aphakic eyes for at least 1 year.

Adolescent↗

PubMed1997

Plasminogen in proliferative vitreoretinal disorders.

OBJECTIVE: Intravitreal fibrin formation is a frequent observation after vitrectomy performed for a variety of vitreoretinal disorders including proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and endophthalmitis. Plasminogen activators (PA) have been used for the management of this postoperative complication. This approach requires the presence of plasminogen, the substrate for PA mediated fibrinolysis, in the vitreal cavity. METHODS: Quantification of plasminogen in the vitreous of 60 patients with PVR, PDR, and macular pucker was performed by streptokinase mediated activation using a chromogenic substrate. The presence of immunoreactive plasminogen was confirmed by immunoblot analysis of vitreal proteins and immunocytochemistry of surgically removed epiretinal membranes. RESULTS: Plasminogen levels were dramatically increased in the vitreous of PVR and PDR patients compared with macular pucker patients and normal controls. Staining for plasminogen in epiretinal membranes was confined to the extracellular matrix. Predominant staining of perivascular areas in PDR specimens indicated that breakdown of the blood-retinal barrier is an important source of intravitreal plasminogen in that condition. CONCLUSION: Plasminogen may play a role in traction membrane formation in PVR and PDR. Our biochemical analysis of presurgical vitreous indicates that there may be abundant substrate for PA mediated fibrinolysis in the vitreous cavity after vitrectomy.

Eye Diseases↗

PubMed1997

Expression and upregulation of microtubule-associated protein 1B in cultured retinal pigment epithelial cells.

PURPOSE: During routine cell culture and under pathologic conditions, human retinal pigment epithelial (RPE) cells lose epithelial characteristics and change their morphology. In this study, changes in gene expression in RPE cells of different generations were evaluated by polymerase-chain-reaction-based differential display mRNA analysis (DD-RT-PCR). METHODS: Total RNA was prepared from freshly isolated and cultured human RPE cells of passages P0 and P3 and was subjected to DD-RT-PCR. One band with enhanced expression was excised, reamplified, and partially sequenced, using a modified dideoxy chain termination approach. Expression of the corresponding protein was ascertained by immunocytochemical analysis. RESULTS: Differential display RT-PCR showed enhanced expression of a specific RNA in P3 cells compared with that in P0 cells. Sequence alignment revealed 98% identity with the 3' end of the coding sequence of human microtubule-associated protein 1B (MAP1B). Confirmation of induced expression of MAP1B mRNA was obtained by PCR with specific primers and by immunocytochemical analysis in cultured RPE cells and in surgically removed epiretinal membranes from patients with proliferative vitreoretinopathy. No expression of MAP1B mRNA or protein was detected in freshly isolated RPE cells. CONCLUSIONS: Differential display RT-PCR in RPE cells with subsequent sequence analysis allows characterization of the maturation- and differentiation-dependent expression of previously undetected genes and gene products in cultured RPE cells.

Animals↗

PubMed1996

A standardized classification of ocular trauma.

BACKGROUND: No internationally standardized classification of ocular trauma terminology has existed heretofore. Despite a growing interest in eye injuries, the absence of a common language continues to impede both clinical care and research. METHODS: A classification was initially developed based on the authors' extensive personal experience. It then under-went repeated reviews over a 3-year period by international ophthalmic specialists. Written and oral suggestions from respondents in 19 countries and from selected ocular trauma experts were considered and incorporated. RESULTS: By always using the entire globe as the tissue of reference, the new classification is unambiguous, consistent, simple, and comprehensive. It provides definitions for the terms commonly used in eye trauma and creates a logical system of injury types. CONCLUSION: In addition to widespread international acceptance by professionals, the new classification has been endorsed by the International Society of Ocular Trauma, the United States Eye Injury Registry, the American Academy of Ophthalmology, the Hungarian Eye injury Registry, the Vetreous Society, and the Retina Society. It can be reasonably expected that the system will ultimately become the standardized international language of ocular trauma.

Eye Injuries↗