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F Faude

Publications and source records attributed to F Faude.

48 records · Page 3Linked to original sources
PubMed1997

Comparison between functional characteristics of healthy and pathological human retinal Müller glial cells.

Enzymatically isolated, noncultured Müller glial cells from human organ donor and patient eyes were studied using the whole-cell-voltage-clamp and the patch-clamp technique. The patients suffered mainly from choroidal melanomas, retinal detachment due to proliferative vitreorentinopathy, glaucomas, and perforating eye injuries. The organ donor eyes were used as a source of corneas for corneal transplantation. Use of the human retinal tissue was approved by the Ethics Committee of the School of Medicine, University of Leipzig. Most of the patient Müller cells showed a marked or complete loss of inwardly rectifying K+ currents, causing a dramatic increase in the input resistance. The zero current potential of the patient Müller cells, which is equivalent to the membrane potential, was significantly reduced (depolarized) as compared with the donor Müller cells. In contrast to the K+ current loss, the Na+ current density was significantly higher in patient Müller cells than in donor Müller cells; the number of Müller cells depicting Na+ currents increased from 33% (3 pA/pF) in donor Müller cells to 85% (about 12pA/pF) in patient Müller cells. Application of glutamate to the Müller cells generated a glutamate-transporter-mediated current, such as that seen in other species. A highly significant increase was noted for the high-affinity Na+-dependent glutamate-transporter-current density in patient Müller cells compared with donor cells. The application of gamma-aminobutyric acid (GABA) evoked, in addition to the GABA transporter currents already known from Müller cells of other mammalian species, GABA(A)-receptor mediated currents in human Müller cells. We found that GABA(A) receptors are expressed in human Müller cells, but not in other nonprimate mammals. Whether a difference exists between the GABA(A) current density in donor and patient Müller cells remains to be seen. The results concerning the disappearance of K+ currents and diminution of the membrane potential may demonstrate early glial changes that may possibly precede pathological neuronal changes, at least in retinas from eyes with choroidal melanomas. In later stages of the diseases, the glial changes may be deleterious for the neurons, because they could diminish glutamate uptake due to the depolarized membrane potential. However, increased extracellular glutamate concentration is toxic for most neurons.

Adolescent↗
PubMed1997

Comparative studies on mammalian Müller (retinal glial) cells.

Müller cells from 22 mammalian species were subjected to morphological and electrophysiological studies. In the 'midperiphery' of retinae immunocytochemically labeled for vimentin, estimates of Müller cell densities per unit retinal surface area, and of neuron-to-(Müller) glia indices were performed. Müller cell densities were strikingly similar among the species studied (around 8000-11,000 mm-2) with the extremes of the horse (< or = 5000 mm-2) and the tree shrew (> or = 20,000 mm-2). By contrast, the number of neurons per Müller cell varied widely, being clustered at 6-8 (in retinae with many cones), at about 16, and at up to more than 30 (in strongly rod-dominated retinae). Isolated Müller cell volumes were estimated morphometrically, and cell surface areas were calculated from membrane capacities. Müller cells isolated from thick vascularized retinae (carnivores, rats, mice, ungulates) were longer and thinner, and had smaller volumes but higher surface-to-volume ratios than cells from thin paurangiotic (i.e. with blood vessels only near the optic disc) or avascular retinae (rabbits, guinea pigs, horses, zebras). In whole-cell voltage-clamp studies, Müller cells from all mammals studied displayed two dominant K+ conductances, inwardly rectifying currents and delayed rectifier currents. TTX-sensitive Na+ currents were recorded only in some species. Based on these data, the following hypotheses are presented, (a) neuron-to-(Müller) glia indices are determined by precursor cell proliferation rather than by metabolic demands; (b) Müller cell volumes depend on available space rather than on the number of supported neurons; and (c) it follows that, the specific metabolic activities of Müller cells must differ greatly between species, a difference that may contribute to distinct patterns of retinal vascularization.

Animals↗
PubMed1997

Mechanisms of graft rejection in the transplantation of retinal pigment epithelial cells.

PURPOSE: The role of activated retinal pigment epithelium (RPE) cells was investigated in the rejection after subretinal transplantation. METHODS: RPE cells from 7 pigmented rabbits were separated and evaluated regarding their MHC class II expression as the sign of activation. The activation of the RPE cells was augmented with a treatment of 1,000 U/ml interferon gamma (IFN-gamma) for 8 days. These cells were then transplanted into 7 albino rabbits. As control, RPE transplantations without a pretreatment were performed in 7 albino rabbits. Six weeks after the transplantation, the transplanted eyes were enucleated and histology was performed. RESULTS: In culture, without IFN-gamma addition, 11.38 +/- 0.94% of the RPE cells presented MHC class II. After IFN-gamma treatment, this quantity increased to 78.26 +/- 1.46% of the RPE cells. These cells transplanted into the rabbits caused an obvious rejection in the transplantation area which was verified histologically. The control group presented a transplantation area without signs of rejection or inflammation. CONCLUSION: In culture, some of the adult RPE cells are activated. These cells may accelerate the rejection cascade after transplantation. An elimination of activated RPE cells from the transplant should be recommended before transplantation.

Animals↗
PubMed1997

The Müller (glial) cell in normal and diseased retina: a case for single-cell electrophysiology.

In the retina of most vertebrates there exists only one type of macroglia, the Müller cell. Müller cells express voltage-gated ion channels, neurotransmitter receptors and various uptake carrier systems. These properties enable the Müller cells to control the activity of retinal neurons by regulating the extracellular concentration of neuroactive substances such as K+, GABA and glutamate. We show here how electrophysiological recordings from enzymatically dissociated mammalian Müller cells can be used to study these mechanisms. Müller cells from various species have Na(+)-dependent GABA uptake carriers, but only cells from primates have additional GABA receptors that activate Cl- channels. Application of glutamate analogues causes enhanced membrane currents recorded from Müller cells in situ but not from isolated cells. We show that mammalian Müller cells have no ionotropic glutamate receptors but respond to increased K+ release from glutamate-stimulated retinal neurons. This response is involved in extracellular K+ clearance and is mediated by voltage-gated (inwardly rectifying) K+ channels which are abundantly expressed by healthy Müller cells. In various cases of human retinal pathology, currents through these channels are strongly reduced or even extinguished. Another type of voltage-gated ion channels, observed in Müller cells from many mammalian species, are Na+ channels. In Müller cells from diseased human retinae, voltage-dependent Na+ currents were significantly increased in comparison to cells from control donors. Thus, the expression of glial ion channels seems to be controlled by neuronal signals. This interaction may be involved in the pathogenesis of retinal gliosis which inevitably accompanies any degeneration of retinal neurons. In particular, Müller cell proliferation may be triggered by mechanisms requiring the activation of Ca(2+)-dependent K+ channels. Ca(2+)-dependent K+ currents are easily elicitable in Müller cells from degenerating retinae and can be blocked by 1 mM TEA (tetraethylammonium). In purified Müller cell cultures, the application of 1 mM TEA greatly reduces the proliferative activity of the cells. These data clearly show that Müller cells are altered in cases of neuronal degeneration and may be crucially involved in pathogenetic mechanisms of the retina.

Animals↗
PubMed1997

Changes in CD44 and ApoE immunoreactivities due to retinal pathology of man and rat.

In cases of retinal light damage, glaucoma, or senile macula degeneration, the loss of retinal neurons is thought to cause alterations of glial cells. We performed immunocytochemical studies on retinae of (i) healthy rats and human donors, (ii) rats exposed to enhanced illumination for 24 months, a procedure which leads to complete loss of photoreceptor cells, (iii) a human donor who had suffered from senile macula (photoreceptor cell) degeneration, and (iv) human donors who had suffered from glaucoma, known to be accompanied by a loss of ganglion cells and other retinal neurons. Furthermore, Müller cells were enzymatically isolated from human glaucomatous retinae. All preparations were subjected to immunocytochemistry for CD44 antigen and Apolipoprotein E (ApoE). In normal rat and human retinae, CD44 immunoreactivity was observed in the microvillous sclerad processes of Müller cells: in human retinae, perivascular (astro-)glial cell processes were also CD44 immunopositive. ApoE immunoreactivity was only found in some perivascular (astro-)glial cell processes of human retinae. Both rat and human Müller cells respond to photoreceptor cell damage by increased, and ectopic, expression of the CD44 antigen. Increased ApoE immunoreactivity was found in Müller cells from degenerative human retinae, but rarely in light-damaged rat retinae. It is concluded that degeneration-related reorganization involves enhanced expression of the glial cell adhesion molecule CD44 as well as elevated activity of the glial lipid transport molecule ApoE.

Aged↗
PubMed1996

Sodium current amplitude increases dramatically in human retinal glial cells during diseases of the eye.

Müller cells, the main macroglial cells of the retina, express several types of voltage and ligand-activated ion channels, including Na+ channels. Using the whole-cell voltage-clamp technique, we studied the expression of Na+ currents in acutely isolated, non-cultivated human Müller cells from retinas of healthy organ donors and patients suffering from different eye diseases. In both types of retinas transient Na+ currents could be recorded from Müller cells. The tetrodotoxin-resistant Na+ currents, which were not completely blocked even at a concentration of 10 microM tetrodotoxin, had a mean current density of 3.0 +/- 3.0 pA/pF (mean +/- SD, n = 10) in Müller cells from donor retinas and of 12.2 +/- 9.6 pA/pF (n = 74) in Müller cells from patient retinas. Only 33.3% of healthy but 88.4% of pathological Müller cells depicted such currents. The GNa+/GK+ ratio was very high in several Müller cells from patient retinas, such that action potential-like activity could be generated after prehyperpolarizing current injection in some of these cells. Apparently, the Na+ channels, due to their negative steady-state inactivation curve (Vh = -84.5 mV), do not influence the lowered membrane potential of the pathological cells, since they are inactivated at these voltages. Currently, we do not have an explanation for the increase in amplitude and frequency of Na+ currents in human Müller cells under pathological conditions. However, the up-regulation of Na+ channels may mirror a basic glial response to pathological conditions, since it has also been found previously in human hippocampal astrocytes from epileptic foci and in rat cortex stab wounds lined by an astrocytic scar.

Electric Conductivity↗
PubMed1987

Central and regional vascular hemodynamics following intravenous milrinone in the conscious rat: comparison with dobutamine.

This study examined the hemodynamic and regional vascular profile of intravenous (i.v.) milrinone during increasing doses (3, 6, 12 micrograms/kg/min, n = 8) and by intraindividual comparison of milrinone and dobutamine (n = 10) in normal conscious rats. At 3 micrograms/kg/min, Milrinone increased coronary and cerebral blood flow (radioactive microspheres 15 +/- 5 microns) (7.7-9.8 and 1.05-1.27 ml/min/g respectively, both p less than 0.05) without significant changes in systemic hemodynamics. At 6 micrograms/kg/min milrinone increased skeletal muscle blood flow (0.19-0.24 ml/min/g, p less than 0.05) along with increases in cardiac output, stroke volume, and stroke work (all p less than 0.05), while systemic vascular resistance decreased (-51%, p less than 0.05). When compared with dobutamine, milrinone caused a greater increase in cardiac output (+26% vs. +17%) and a greater reduction in systemic vascular resistance. Milrinone and dobutamine increased renal, intestinal, cerebral, and coronary flow to a similar extent, but only milrinone enhanced hepatic arterial blood flow (+26%, p less than 0.05) and tended to increase flow to skeletal muscle (+35%, p = 0.07). We conclude that milrinone exerts significant regional vasodilating effects in a conscious rat model, being most prominent in the coronary and cerebral circulations at a dosage that does not alter central hemodynamics. At higher doses, milrinone causes a balanced increase in regional blood flow including enhanced flow to skeletal muscle. The hemodynamic (particularly as compared with dobutamine) and regional vascular profile of milrinone suggests a predominant vasodilating effect in the rat. Given a similar limited response of rat and diseased human myocardium to milrinone, these findings may have important clinical implications.

Animals↗
PubMed1987

Blood flow distribution within skeletal muscle during exercise in the presence of chronic heart failure: effect of milrinone.

Recent studies suggest that, in the presence of heart failure, the capability of skeletal muscle to utilize delivered flow may be impaired due to maldistribution of blood flow within working muscle. Similarly, this mechanism could explain the failure of drugs to improve maximal oxygen consumption (VO2max) immediately. Accordingly, we assessed muscular blood flow distribution (ml/min/g, radioactive microspheres, 15 +/- 5 micron) among and within working muscle, VO2max, and arterial lactate in a rat preparation of myocardial infarction and heart failure (infarct size 36.0 +/- 3.3% of the left ventricle, n = 9), and in sham-operated animals (n = 11). Data were obtained at maximal treadmill exercise during alternate infusions of milrinone and saline. Total skeletal muscle blood flow during exercise was significantly lower in the infarction group (p less than .05 vs sham); reduced blood flow was primarily attributed to decreased flow to oxidative working muscle such as soleus and the red portion of gastrocnemius, whereas blood flow to glycolytic muscle portions (e.g., gastrocnemius white, vastus lateralis white) was similar in the infarction and sham-operated groups. Milrinone increased flow to the glycolytic working muscle portions in sham-operated animals (e.g., vastus lateralis white, 0.23 vs 0.29, p less than .05); by contrast, blood flow to the oxidative muscle fibers was increased in the infarction group (e.g., gastrocnemius red, 1.45 vs 1.87, p less than .05). Arterial lactate levels at similar workloads during exercise were higher in the infarction group (p less than .05). Neither lactate nor VO2max were significantly altered with milrinone in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Central and regional vascular hemodynamics of milrinone in experimental heart failure: comparison with captopril and dobutamine].

The present study was designed to evaluate the regional vascular profile of milrinone in the setting of experimental heart failure. Utilizing the rat model of myocardial infarction and failure (average infarct size 28%), we measured cardiac output (CO), arterial pressure (MAP), LVEDP, heart rate and systemic vascular resistance, as well as regional blood flow (radioactive microspheres 15 +/- 5 microns) before and after milrinone i.v. (20 microns/kg bolus, 3 micrograms/kg/min infusion) in the conscious state (LVEDP 22 mm Hg versus 10 mm Hg in the sham-operated group, p less than 0.01). Similarly, central hemodynamics and regional blood flow were determined before and after dobutamine or captopril, administering equipotent doses. Milrinone reduced LVEDP more than dobutamine, both more than captopril; MAP was decreased by captopril only. Although all three drugs reduced SVR to a similar extent and increased CO, a quite different blood flow distribution occurred. Improvement in flow to skeletal muscle and splanchnic circulatory bed was exerted by milrinone only. Thus, milrinone attenuated the vasoconstriction in those circulations known to be impaired in heart failure. In contrast to captopril, the effects of milrinone on renal perfusion were modest. These results demonstrate the potent vasodilator activity of milrinone, which is independent of its direct-positive inotropic effects, being most prominent in the splanchnic, coronary and skeletal muscle circulation. The latter might have clinical relevance since improved muscular flow during exercise is likely to improve exercise capacity in heart failure after long-term treatment.

Animals↗
PubMedDate not supplied

360 degrees retinectomy in severe anterior PVR and PDR.

We reviewed 30 cases of 360 degrees retinectomy in advanced anterior PVR or PDR with anterior traction. The preoperative visual acuity was light perception or hand motions. In all cases, a 360 degrees retinectomy with silicone oil tamponade was performed. After a mean follow-up of 10 months, the retina was attached in 83% and the visual acuity had improved in 47% of the patients. The mean visual field in patients with a visual acuity of more than counting fingers extended to 29 degrees nasally and 38 degrees temporally. Hypotony was seen in 6 patients, of whom two developed keratopathy. In conclusion, eyes with severe PDR or PVR and a preoperative low visual acuity can be treated successfully with 360 degrees retinectomy when conventional methods have failed. The patients can regain an ambulatory visual acuity and a visual field.

Diabetic Retinopathy↗