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Biomedical subjects

F Faude

Publications and source records attributed to F Faude.

At least 37 records · Page 2Linked to original sources
PubMed2000

Age- and disease-related changes of calcium channel-mediated currents in human Müller glial cells.

PURPOSE: To determine whether the expression of voltage-gated Ca2+ channels in human Müller glial cells changes during normal aging and in cells from patients with proliferative vitreoretinopathy (PVR). METHODS: Müller cells were enzymatically isolated from retinas of healthy donors and from excised retinal pieces of patients with PVR, and the whole-cell, voltage-clamp technique was used to characterize the current densities of transient, low-voltage-activated calcium channels and of sustained. high-voltage-activated calcium channels, respectively. To obtain maximal currents through both channel types, Na+ ions were used as the charge carrier. RESULTS: During normal aging, Müller cells developed a hypertrophy, as indicated by an increase of the cell membrane capacitance. The mean membrane capacitance of cells from aged donors (> or = 60 years old) was elevated by 25% compared with cells from younger donors. The hypertrophy was not accompanied by a changed density of low-voltage-activated currents, whereas the density of the high-voltage-activated currents was enhanced by 76%. The density of the high-voltage-activated currents increased in correlation with the increase of the cell membrane capacitance and with the age of the donors. In the case of PVR, Müller cells displayed a strong hypertrophy accompanied by a downregulation of both current types by approximately 65%. CONCLUSIONS: Both normal aging and PVR cause a gliotic reactivity of human Müller cells, as indicated by their hypertrophy. The type of reactivity, however, differs between the two conditions. Normal aging is accompanied by an increased expression of voltage-gated Ca2+ channels, whereas in PVR Ca2+ channel expression is decreased.

Adult↗
PubMed2000

The local and systemic secretion of the pro-inflammatory cytokine interleukin-6 after transplantation of retinal pigment epithelium cells in a rabbit model.

The rejection of retinal pigment epithelium (RPE) allografts is one of the major problems for long-term success after retinal transplantation. However, the details of the immunological interactions in the subretinal space after transplantation are still unknown. The aim of our study was to investigate the role of IL-6 in the rejection process in the subretinal space and to use IL-6 monitoring for a possible early sign of rejection after transplantation of allogeneic RPE cells. For this we used a model of transplanting pigmented RPE cells, either activated in vitro with 1000 U/ml interferon-gamma (IFN-gamma) for 8 days or non-activated, into 30 albino rabbits. The IL-6 was investigated 3, 5, 7, 9 and 14 days after transplantation. Additionally, sham operated animals and the untreated eyes served as controls. At these time-points the animals were killed, the liquid in the vitreous cavity and serum was collected and the IL-6 present in these samples was quantified with an enzyme-linked immunosorbent assay. Under these conditions, IL-6 was detected in the liquid of the vitreous cavity and in the serum of all RPE-transplanted rabbits. In the group receiving activated RPE two cytokine peaks were measured, 3 and 7 days after transplantation in the vitreous cavity. In non-activated grafts, a maximum was detected on the 5th day after transplantation. Generally, the detected quantity of IL-6 depended on the host status and on the phase of rejection. No significant changes were seen in the sera from either group. Possibly, the host RPE cells are the main source of this interleukin in the transplantation area. The measuring of IL-6 in the rejection model suggests that it plays a role in the immune cascade in the subretinal space.

Animals↗
PubMed1999

[Activated protein C resistance in patients with central retinal vein occlusion in comparison to patients with a history of deep-vein thrombosis and a healthy control group].

BACKGROUND: The recently described "APC resistance" caused by a mutant form of factor V (factor V Leiden) is the most frequent cause of hereditary thrombosis. This study was carried out to investigate the association between activated protein C resistance and central retinal vein occlusion (CRVO). We evaluated the prevalence of APC resistance in patients with CRVO, patients with a history of deep-vein thrombosis, and a healthy control group. PATIENTS AND METHODS: We examined 107 patients with CRVO, 112 patients with deep-vein thrombosis and 70 healthy individuals. The test performed was a modified APC-resistance assay using factor V-deficient plasma. RESULTS: We identified APC resistance in 5.6 % of patients with CRVO and in 5.7 % of the control group. All carriers were heterozygous. In the deep-vein thrombosis group 23.2 % tested positive for APC resistance. Four patients were homozygous and 22 were heterozygous carriers. CONCLUSION: These results indicate that APC resistance has no major role in the pathogenesis of CRVO. Routine testing for the presence of factor V Leiden mutant in CRVO is not necessary.

Adult↗
PubMed1999

[A survey of clinically used drugs in PVR: a review].

Colchicine, corticosteroids, daunomycin, fluorouracil, heparin and retinoids have been used in man and show an effect in different stages of the development of PVR. In this survey the effect of each drug is described and the clinical studies are discussed. This survey shows that there are many drugs that in addition to surgery might influence the natural course of clinical PVR during different stages. However, the only drug for which a significant reduction in the number of reoperations has been demonstrated in a randomized prospective trial is daunomycin. Literature search by medline.

Animals↗
PubMed1999

Human Müller glial cells: altered potassium channel activity in proliferative vitreoretinopathy.

PURPOSE: To determine differences of K+ channel activity between Müller glial cells obtained from retinas of healthy human donors and of patients with retinal detachment and proliferative vitreoretinopathy. METHODS: Müller cells were enzymatically isolated from retinas of healthy donors and from excised retinal pieces of patients. The whole-cell and the cell-attached configurations of the patch-clamp technique were used to characterize the current densities of different K+ channel types and the activity of single Ca2+ -activated K+ channels of big conductance (BK). RESULTS: Cells from patients displayed a less negative mean membrane potential (-52.8 mV) than cells from healthy donors (-80.6 mV). However, the membrane potentials in cells from patients scattered largely between -6 and -99 mV. The inwardly rectifying K+ permeability in cells from patients was strongly reduced (0.3 pA/pF) when compared with cells from healthy donors (6.0 pA/pF). At the resting membrane potential, single BK channels displayed a higher mean activity (open probability, Po, and channel current amplitude) in cells from patients (Po, 0.30) than in cells from healthy donors (Po: 0.03). The variations of BK current amplitudes were correlated with the variations of the membrane potential. CONCLUSIONS: The dominant expression of inwardly rectifying channels in cells from healthy donors is thought to support important glial cell functions such as the spatial buffering of extracellular K+. The downregulation of these channels and the less negative mean membrane potential in cells from patients should impair spatial buffering currents and neurotransmitter clearance. The increased activity of BK channels may support the proliferative activity of gliotic cells via feedback regulation of Ca2+ entry and membrane potential.

4-Aminopyridine↗
PubMed1999

The activity of a transient potassium current in retinal glial (Müller) cells depends on extracellular calcium.

The modulating effects of varying extracellular concentrations of Ca2+ ([Ca2+]e) and of other divalent cations on the fast transient (A-type) K+ current (I(A)) of freshly isolated Muller glial cells from rabbit and human retinae were studied with the whole-cell patch-clamp method. The I(A) of Miller cells was voltage-independently blocked by extracellular 4-aminopyridine (4AP) with a 50 % reduction achieved at 0.94 mM 4AP. The I(A) amplitude was elevated by increased extracellular [K+]. Elevation of the [Ca2+]e had three effects on the glial I(A): (i) it concentration-dependently shifted both the activation and inactivation curves towards less negative membrane potentials, (ii) it increased the peak current amplitude, and (iii) it slowed down the activation and inactivation kinetics. Particularly at depolarized membrane potentials, the I(A) was enlarged and broadened when the [Ca2+]e was increased. Various divalent cations also exerted these effects, although at different concentrations. While Zn2+, Cd2+, Cu2+ and Pb2+ modulated the I(A) in the micromolar range, Mg2+ and Ba2+ had effects in the millimolar range. Extracellular acidification produced a positive shift in the voltage dependence of I(A) gating. However, alterations of the extracellular pH did not abolish the Ca2+ effects on I(A); this indicates that protons and Ca2+ ions mediate their effects on glial K(A) channels by different mechanisms or binding sites, respectively. Physiological (i.e., activity-dependent) changes of the extracellular concentration of divalent cations and of the extracellular pH should influence the retinal excitability via modulation of glial K+ currents. The activation of glial I(A) by divalent cations at depolarized voltages supports a repolarization and, therefore, the maintainance of a hyperpolarized glial membrane potential during periods of increased neuronal activity.

4-Aminopyridine↗
PubMed1998

Spermine/spermidine is expressed by retinal glial (Müller) cells and controls distinct K+ channels of their membrane.

There is recent evidence that polyamines such as spermine (spm) and spermidine (spd) may act as endogenous modulators of the activity of inwardly rectifying K+ channels. This type of K+ channels is abundantly expressed by retinal glial (Müller) cells where they are involved in important glial cell functions such as the clearance of excess extracellular K+ ions. This prompted us to study the following questions, i) do mammalian Müller cells contain endogenous spm/spd?; ii) do Müller cells possess the enzymes (e.g., ornithine decarboxylase, ODC) necessary to produce spm/spd?; and iii) does application of exogenous spm/spd exert specific effects onto inwardly rectifying K+ channels of Müller cells? Immunocytochemical studies were performed on histological sections of guinea-pig, rabbit, porcine, and human retinae, and on enzymatically dissociated Müller cells. Whole-cell and patch-clamp recordings were performed on enzymatically dissociated porcine and guinea-pig Müller cells. All above-mentioned questions could be answered with "yes." Specifically, the majority of Müller cells were labeled with antibodies directed to spm/spd, both within retinal sections and enzymatically isolated from retinal tissue. Müller cells in normal retinae express low levels of ODC but increase this expression markedly in cases of retinal pathology such as experimental epiretinal melanoma. Externally applied polyamines (1 mM) reduce (predominantly inward) whole-cell K+ currents, with the efficacies being spm > spd > put. If applied at the inside of membrane patches, spm (1 mM) blocks completely the outward currents through inwardly rectifying K+ channels but fails to affect the activity of large conductance, Ca2+-activated K+ channels. It is concluded that Müller cells contain endogenous channel-active polyamines, the synthesis of which may be up-regulated in pathological situations, and which may be involved in the control of both glial function and cell proliferation.

Adolescent↗
PubMed1998

Alterations of potassium channel activity in retinal Müller glial cells induced by arachidonic acid.

Arachidonic acid, which is thought to be involved in pathogenetic mechanisms of the central nervous system, has been shown previously to modulate neuronal ion channels and the glutamate uptake carrier of retinal glial (Müller) cells. We have used various configurations of the patch-clamp technique to determine the effects of arachidonic acid on the K+ currents of freshly isolated Müller glial cells from rabbit and human. Arachidonic acid reduced the peak amplitude of the transient (A-type) outward K+ currents in a dose-dependent and reversible manner, with a 50% reduction achieved by 4.1 microM arachidonic acid. The inward rectifier-mediated currents remained unchanged after arachidonic acid application. The amplitude of the Ca(2+)-activated K+ outward currents (KCa), which were blocked by 1 mM tetraethylammonium chloride and 40 nM iberiotoxin, respectively, was dose-dependently elevated by bath application of arachidonic acid. The activation curve of the KCa currents shifted towards more negative membrane potentials. Furthermore, arachidonic acid was found to suppress inwardly directed Na+ currents. In cell-attached recordings with 3 mM K+ in the bath and 130 mM K+ in the pipette, the KCa channels of rabbit Müller cells displayed a linear current-voltage relation, with a mean slope conductance of 102 pS. In excised patches, the slope conductance was 220 pS (150 mM K+i/130 mM K+o). The opening probability of the KCa channels increased during membrane depolarization and during elevation of the free Ca2+ concentration at the intracellular face of the membrane patches. Bath application of arachidonic acid caused a reversible increase of the single-channel opening probability, as well as an increase of the number of open channels. Arachidonic acid did not affect the single-channel conductance. Since arachidonic acid also stimulates the KCa channel activity in excised patches, the action of arachidonic acid is assumed to be independent of changes of the intracellular calcium concentration. Our results demonstrate that arachidonic acid exerts specific effects on distinct types of K+ channels in retinal glial, cells. In pathological cases, elevated arachidonic acid levels may contribute to prolonged Müller cell depolarizations, and to the initiation of reactive glial cell proliferation.

Animals↗
PubMed1998

[A retrosellar arachnoid cyst as a rare cause of homonymous hemianopsia].

BACKGROUND: Arachnoidal cysts are cystic lesions filled with a cerebrospinal-fluid-like content within the leptomeninges. Usually arachnoidal cysts represent a congenital malformation. Clinical signs (increased intracranial pressure and/or neurological defects) may become apparent in children or young adults. PATIENT: A sixteen year old boy was referred to our outpatient clinic because of blurred vision in both eyes since five days. The patient complained of cephalgia and of an increased sleep requirement in the last two weeks. Morphological findings were within the normal range. The visual acuity was 0.7 in the right eye and 0.2 in the left eye. The visual fields showed an incomplete homonymous hemianopia to the right. The CT and MRI revealed a retrosellar arachnoidal cyst. Two weeks after fenestration of the cyst the visual acuity had risen to 1.3 in both eyes and the visual field defects had disappeared nearly completely. CONCLUSION: A retrosellar arachnoidal cyst can impair the visual pathway. Early fenestration prevents permanent damage.

Adolescent↗
PubMed1998

Immunological problems of transplantation into the subretinal space.

The objective of retinal transplantation is to substitute destroyed or degenerated retina to improve visual function. Photoreceptors and retinal pigment epithelium cells of embryonic and nonembryonic origin have been transplanted into the subretinal space in different animal models. Recently, retinal cells have also been used for transplantation in untreated or immunosuppressed patients with retinitis pigmentosa and age-related macular degeneration. Transplants performed in animals such as the RCS rat have maintained retinal function at the transplantation site for long periods of time, although such transplantations in humans have not proved conclusively, to date, whether there is a real effect or not. One reason for this phenomenon seems to be an immune response to transplanted retinal cells at the transplantation site. The detectable rejection process shows that the posterior part of the eye is not absolutely immunologically privileged and that rejection is a serious problem in human retinal transplantation. Many questions concerning transplantation technique, graft treatment and postoperative treatment will be answered through more intensive experiments and clinical trials regarding the immunology. However, rejection of transplanted material is one of the main reasons why retinal transplantation has not yet proved successful.

Animals↗
PubMed1998

Secretion of cytokines by human choroidal melanoma cells and skin melanoma cell lines in vitro.

The selective secretion of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), basic fibroblast growth factor (b-FGF) and transforming growth factor beta 1 (TGF beta-1) in tissue culture of choroidal melanomas and two established skin melanoma cell lines was investigated with ELISA analysis. Values of choroidal melanoma cells were compared with the melanoma cell lines and human fibroblasts as a physiological control. High secretion of IL-6 was detectable in choroidal melanoma cultures but not in the cell lines. IL-8 secretion was found in all melanoma cultures. However, IL-10 was only secreted by one skin melanoma cell line and in choroidal melanoma cell cultures. B-FGF secretion by choroidal melanomas was higher than by cell lines. No differences were seen in the amounts of TGF beta-1 produced by melanoma cells. Human fibroblasts produce higher amounts of IL-6 and IL-8 but lower of b-FGF in vitro in contrast to the melanoma cells. The secretion of cytokines by choroidal melanoma cells suggests an important role of these soluble factors in the interaction of tumour and healthy tissue.

Choroid Neoplasms↗
PubMed1997

Mammalian retinal glial (Müller) cells express large-conductance Ca(2+)-activated K+ channels that are modulated by Mg2+ and pH and activated by protein kinase A.

The cell-attached and excised patch configurations of the patch clamp technique were used to characterize Ca(2+)-activated maxi-K+ channels in freshly-isolated Müller glial cells. The cells were dissociated from postmortem adult human and porcine retinas. The maxi-K+ channels in Müller cells of both species display a single channel conductance of 175 pS in cell-attached and inside-out patches (125/110 mM K+). The channels are activated by membrane depolarization and by elevation of intracellular Ca2+. In the presence of 10(-5), 10(-4), and 10(-3) M intracellular free Ca2+, the half-activation voltages are +7.2, -26.6, and -47.5 mV, respectively. The half-activation-[Ca2+] at +10 mV is 8.1 microM, and the Hill coefficient of Ca2+ binding is 1.7, Ba2+ exerts a voltage-dependent block of the open-state probability. The maxi-K+ channels of Müller cells are activated by raising of the intracellular pH as well as by Mg2- ions at the cytosolic face of the channels. Phosphorylation of the channel after cytosolic addition of the catalytic subunit of a cAMP dependent protein kinase in the presence of Mg-ATP caused a shift of the activation curve to negative membrane potentials. Between -40 and -80 mV membrane potentials, the open-state probability rose to 190.3% of the control value (100%) after phosphorylation of the channel. Therefore, phosphorylation enhances sensitivity of the channels to Ca2+ and voltage. The maxi-K+ channels may provide a link between second messenger systems and membrane conductance of retinal Müller cells and may have an important function in repolarization of the Müller cell membrane and, therefore, in the maintainance of the retinal spatial K+ buffering mechanisms.

Adenosine Triphosphate↗
PubMed1997

Loss of inwardly rectifying potassium currents by human retinal glial cells in diseases of the eye.

We compared the inward K+ currents of Müller glial cells from healthy and pathologically changed human retinas. To this purpose, the whole-cell voltage-clamp technique was performed on noncultured Müller cells acutely isolated from human retinas. Cells originated from retinas of four healthy organ donors and of 24 patients suffering from different vitreoretinal and chorioretinal diseases. Müller cells from organ donors displayed inward K+ currents in the whole-cell mode similar to those found in other species. In contrast, this pattern was clearly changed in the Müller cells from patient retinas. In whole-cell recordings many Müller cells had strongly decreased inward K+ current amplitudes or lost these currents completely. Thus, the mean input resistance of Müller cells from patients was significantly increased to 1,129 +/- 812 M omega, compared to 279 +/- 174 M omega in Müller cells from healthy organ donor retinas. Accordingly, since the membrane potential is mainly determined by the K+ inward conductance in healthy Müller cells, a large amount of Müller cells from patient retinas had a membrane potential which was significantly lower than that of Müller cells from control eyes. The mean membrane potentials were -37 +/- 24 mV and -63 +/- 25 mV for patient and donor Müller cells, respectively. The newly described membrane characteristic changes of Müller cells from patient eyes are assumed to interfere severely with normal retinal function: (1) the retinal K+ homeostasis, which is partly regulated by the Müller cell-mediated spatial buffering, should be disturbed, and (2) the diminished membrane potential should influence voltage-dependent transporter systems of the Müller cells, e.g., the Na(+)-dependent glutamate uptake.

Barium↗
PubMed1997

[Autologous thrombocyte administration in treatment of idiopathic macular foramen].

BACKGROUND: Recent studies have shown the usefulness of pars plana vitrectomy with the use of growth factors in the treatment of macular holes. Autologous platelet concentrates contain many growth factors to stimulate glial wound healing. PATIENTS: Nineteen patients with idiopathic macular hole underwent vitrectomy, membrane peeling, air injection and installation of autologous platelet concentrate (0.1 ml). The platelet concentrate contained a mean of 1.8 x 10(9) platelets/ml. RESULTS: The anatomic success rate in stage 2 macular hole was 100%, in stage 3, 82% and in stage 4, 50%. Visual acuity improved in all patients with stage 2 (two lines) and in 73% of stage 3 at least (one line). CONCLUSION: Platelets are effective in the treatment of macular holes due to the high amount of different growth factors (PDGF, EGF, bFGF, IGF-1) which have a high affinity binding to Müller cells helping to seal the hole by photoreceptor adaption.

Aged↗