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M Doly

Publications and source records attributed to M Doly.

At least 19 recordsLinked to original sources
PubMed1998

Light-induced variations of retinal sensitivity in rats.

PURPOSE: ERG responses were measured as a function of Ganzfeld luminance to evaluate functional damage induced by light on rat retinas. METHODS: Wistar rats were exposed to a fluorescent light of 1700 lux for 12 h, 24 h, 48 h and 72 h. We recorded ERGs before and one night after exposure, then 3, 8, 15, 22 and 29 days later. The b- and PIII-wave amplitudes were plotted against luminance for each group at each recovery time. RESULTS: The retinal damage induced by a pupillary illuminance of 1700 lux ranged from low to severe as exposure duration increased from 12 h to 72 h, respectively. We observed an effect immediately after light exposure but no improvement during the recovery period. The b-wave amplitude was reduced by 40, 60, 80 and 90 percent after 12, 24, 48 and 72 h of light exposure, respectively; the PIII-wave amplitude was reduced by 30, 40, 70 and 90 percent after these respective exposures. The Ganzfeld luminance eliciting a 50 microV b-wave amplitude increased significantly with exposure duration, but the luminance eliciting the maximal b-wave amplitude was not dependent on this duration. Hence we suggest that the ERG decrease is due to a reduction in photoreceptor number. CONCLUSIONS: We present a full analysis of the electrophysiological parameters recorded from light-exposed or non-exposed rats. This model is a useful tool to study in vivo retinal degeneration.

Animals↗
PubMed1997

Experimental electroretinographic exploration of retinal ischemia: preventive use of free radical scavengers and anti-PAF agents.

Electroretinographic exploration is an effective approach to evaluate retinal function. In order to investigate physiopathological mechanisms and evaluate potentially protective therapies for retinal ischemia, we developed three experimental models: the first two on isolated retina, with ischemia induced by either stopping perfusion or clamping the ophthalmic artery, and the third, in vivo, with ischemia induced by ocular hypertonia. Since free radicals are implicated in the formation of post-ischemic lesions, we evaluated the protective effects of drugs known to be free radical scavengers and of an immunomediator antagonist, an anti-PAF (platelet activating factor) agent.

Analysis of Variance↗
PubMed1997

Direct measurement of free radicals in ischemic/reperfused diabetic rat retina.

Electron paramagnetic resonance (EPR) spectroscopy was used to directly measure free radical generation in ischemic/reperfused diabetic rat retina. Tissue was frozen at 77 degrees K after 90 min ischemia, and 90 min ischemia followed by 1 min, 3 min, 5 min, and 24 hours reperfusion, respectively. After 90 min of ischemia followed by 1 min, 3 min, 5 min, and 24 hours of reperfusion (n = 10 in each group), free radical signal intensity was increased from its diabetic nonischemic control value of 12 +/- 3 arbitrary units to 58 +/- 6 (P < 0.05), 62 +/- 7 (P < 0.05), 32 +/- 5 (P < 0.05), and 14 +/- 4 arbitrary units, respectively. The peak intensity of free radical production was observed after 90 min ischemia followed by 3 min of reperfusion; therefore, this time point was selected to study the retinal free radical production in superoxide dismutase (conjugated with polyethylene glycol, PEG-SOD) and EGb 761 (Ginkgo biloba extract)-treated groups. With 7,500, 15,000, and 30,000 U/liter of SOD, and 25, 50, and 100 mg/kg of EGb 761, a dose-dependent reduction in oxygen free radical production was detected, respectively, which may be responsible for the attenuation of abnormal postischemic function in ischemic and reperfused diabetic retina.

Animals↗
PubMed1996

[Suppression of platelet activating factor effects (PAF) on the retina by G-proteins inhibitors].

The Platelet Activating Factor (PAF) have been shown to alter the transretinal potential recorded from light stimulated isolated retina. In the present study, we investigated the effect of cholera and pertussis toxins on PAF-induced electroretinogram (ERG) impairment. Administrated alone, 2.10(-7) M PAF induced a very marked and rapid drop in the b-wave amplitude of the ERG. When 75 micrograms/l of cholera toxin was coadministrated with PAF (2.10(-7) M) into the perfusion solution, the fall of the b-wave was not observed, suggesting that PAF effect on retinal function was mediated through GTP-binding protein (G-protein). Similarly, low-dose of pertussis toxin (5 micrograms/l) 1) were sufficient to antagonize PAF (2.10(-7) M) consequence on the ERG. Our results suggest that the irreversible and deleterious effect of PAF on ERG is mediated by a G-protein mechanism, located in the neural retina.

Animals↗
PubMed1995

Protective effect of a specific PAF antagonist on vincristine-induced experimental retinopathy.

The alkaloid vincristine displays considerable toxicity, particularly for the retina. This type of retinopathy being an inflammatory disease, we measured the effects of a new hetrazepine platelet activating factor antagonist, BN 50730, on a vincristine-induced retinopathy in the rat. Retinal impairments were established by recording several parameters of the electroretinogram obtained from isolated retina. Our results indicate that 1) the increase in PIII duration induced by vincristine is significantly reduced by BN 50730 administration 2) the decrease in the amplitude of the PIII/b wave ratio caused by vincristine is partially inhibited by treatment with BN 50730. These experiments suggest that platelet activating factor is implicated in vincristine retinopathy and demonstrate the therapeutic effect of a specific antagonist of the mediator.

Animals↗
PubMed1995

Inhibition of platelet-activating factor-induced retinal impairments by cholera and pertussis toxins.

Platelet-activating factor (PAF) has been shown to alter the trans-retinal potential recorded from light-stimulated isolated retina. In the present study, we investigated the effect of cholera and pertussis toxins on PAF-induced impairment of the electroretinogram (ERG). Administered alone, 2 x 10(-7) M PAF induced a very marked and rapid drop in the b-wave amplitude. When 75 micrograms/l of cholera toxin was coadministered with PAF in the perfusion solution, no b-wave drop was observed, suggesting that the effect of PAF on retinal function was mediated by GTP-binding protein (G protein). Similarly, a low dose of pertussis toxin (5 micrograms/l) was sufficient to antagonize the action of PAF on the ERG. Our results suggest that the irreversible and deleterious effect of PAF on ERG is mediated by a G protein mechanism, located in the neural retina.

Animals↗
PubMed1995

Antioxidant effect of a Ginkgo biloba extract (EGb 761) on the retina.

Several investigations have recently shown that the retina is very sensitive to oxygenated free radicals (O2-, OH.) at the origin of the membrane phospholipids peroxidation. Peroxy radical (ROO.) release is responsible for the induction of electrophysiological disturbances leading to retinopathy development. As Ginkgo biloba extract (EGb 761, IPSEN, France) was reported to scavenge primary (O2-, OH.) and secondary (ROO.) free radicals, we evaluated its antioxidant effect on retinas of albino rats submitted to different types of aggressors. On isolated rat retina, EGb 761 given orally significantly protected against lipoperoxidation induced by a mixture of ferrous sulfate and sodium ascorbate added to the perfusion solution. With EGb 761, the decrease of the b-wave ERG amplitude was less pronounced and the retina survival was increased. EGb 761 was also effective against ischaemia-reperfusion disorders due to occlusion of the central retinal artery or by intraocular hypertony. Like other antioxidants such as superoxide dismutase tested on these models, EGb 761 significantly attenuated, according to a dose-response effect, the free-radical injury. EGb 761 reduces the decrease of the b-wave amplitude, the oedema, necrosis and ion homeostasis disturbances. Xenobiotics are also responsible for the retinotoxicity partly due to free radicals and PAF release. We noted an EGb 761 dose-dependent protective effect against acute and chronic chloroquine toxicity to the retina. The deleterious effect of chloroquine was characterized by a delayed b-wave and an asymmetry of the signal with slow declining b-wave. After EGb 761 treatment, the ERG aspect was partially normal. In conclusion, EGb 761, by its general free-radical scavenger properties, is an antioxidant that inhibits or reduces the functional and morphological retina impairments observed after lipoperoxide release.

Animals↗
PubMed1994

Transduction of the light message: from the photon to the optic nerve.

Retinal transduction consists of the conversion of a physical stimulus, light, into an electrophysiological signal. This conversion takes place in several stages. First of all, at the photoreceptor level, via a sequence of molecular activations and deactivations, the detection of light results in an hyperpolarization of the cell membrane. This initial electrical signal is then relayed onto the functional cells of the retina. The bipolar cells are the first associated neurons, responding to the light stimulus by either hyperpolarization (OFF), or depolarization (ON). The second associated neurons are the ganglion cells where the ON-OFF duality also operates and whose fibers make up the optic nerve. In coloured photopic vision, the photoreceptor--bipolar cell--ganglion cell circuit is direct. For the cone-bipolar cell transmission, horizontal cells delimit excitatory (center) and inhibitory (surround) zones at the origin of the receptive field. In scotopic vision, however, i) there is only a single class of bipolar cells, that depolarize in response to light, and ii) the bipolar-ganglion cell connection is not direct. Here, the AII amacrine cells are responsible for the inhibition of the OFF ganglion cells directly connected to them or for the excitation of the ON ganglion cells via ON bipolar cells of the cone circuit. Finally, in mesopic vision, the sensory message originates in rods, and is subsequently relayed by the cone circuit via gap junctions between photoreceptors.

Animals↗
PubMed1993

Modification of ischemia/reperfusion-induced ion shifts (Na+, K+, Ca2+ and Mg2+) by free radical scavengers in the rat retina.

We investigated the contribution of scavenging of oxygen free radicals to retinal ion contents during ischemia and reperfusion with the use of superoxide dismutase (SOD, Sigma), allopurinol (Sigma), EGB 761 (extract of Ginkgo biloba, Tanakan, IPSEN, Paris, France) and allopurinol plus EGB 761 in the rat. SOD (15,000 U/kg/day), allopurinol (50 mg/kg/day), EGB 761 (100 mg/kg/day) and allopurinol (50 mg/kg/day) plus EGB 761 (100 mg/kg/day) were administered for 10 days, respectively. Then, the eyes were subjected to 90 min of ischemia followed by 4 and 24 h of reperfusion, respectively. Retinal Na+, K+, Ca2+ and Mg2+ contents were measured by atomic absorption spectrophotometry after the washing out of blood and extracellular fluid from the vasculature. SOD, EGB 761 and the combination of EGB 761 with allopurinol significantly reduced the ischemia/reperfusion-induced Na+ and Ca2+ accumulation and K+ loss in ischemic/reperfused retinal tissue. Allopurinol alone failed to reduce the maldistribution of Na+, Ca2+ and K+ induced by ischemia/reperfusion in the retina. Neither intervention inhibited the cell Mg2+ loss which was observed during ischemia and reperfusion. Despite the responsible mechanisms remaining controversial, many studies confirmed that ischemia/reperfusion could trigger very sudden metabolic, electrophysiologic, morphologic and functional changes. There is general agreement that major ionic shifts are implicated; what triggers these changes is unclear, although many investigators believe that free radicals and oxidant stress may be important.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Prevention of chloroquine-induced electroretinographic damage by a new platelet-activating factor antagonist, BN 50730.

Chloroquine retinopathy is a severe toxic retinal impairment which may result in loss of vision by alterations of the retinal pigment epithelium and photoreceptors. Currently, there is no specific treatment for this retinopathy. Platelet-activating factor (PAF) is known to modulate retinal function and is one of the major immunomediators of the retina. In order to test the possible involvement of PAF in chloroquine-induced retinopathy and the effectiveness of PAF antagonists in the prevention of this condition, we investigated the effects of BN 50730, a specific PAF antagonist, on the electroretinogram (ERG) of the isolated rat retina exposed to chloroquine. When retinas from normal rats were perfused with chloroquine (10(-6) M), a marked and rapid decrease in b-wave amplitude was observed. In contrast, chloroquine had no effect on the b-wave of the retina isolated from animals pretreated with the PAF antagonist BN 50730 (30 mg/kg/day, i.p., for 5 days). The results obtained indicate that (i) chloroquine is a toxic drug for retinal function, (ii) PAF plays a key role in the mediation of chloroquine retinopathy and (iii) PAF antagonists may constitute valuable agents for the treatment of this retinal impairment.

Animals↗
PubMed1993

Ischaemia and reperfusion-induced injury in rat retina obtained from normotensive and spontaneously hypertensive rats: effects of free radical scavengers.

The authors have studied the effects of free radical scavengers, superoxide dismutase (SOD) and extract of Ginkgo biloba (EGb 761, flavone-rich extract) on ion shifts (Na, K and Ca) induced by ischaemia and reperfusion in rat retina obtained from normotensive and spontaneously hypertensive rats. Eyes were subjected to 90 min of ischaemia by occlusion of the retinal artery, followed by 4 and 24 hours of reperfusion. SOD (15,000 U/kg, i.v.) or EGb 761 (50 mg/kg, per os) was administered in a daily dose for 10 days. In the drug-free control groups, 90 min of ischaemia significantly increased tissue Na gains from their pre-ischaemic control values of 63 +/- 7 microM/g dry weight (in retina obtained from normotensive rats) and 76 microM/g dry weight (in retina obtained from hypertensive rats) to 89 +/- 9 microM/g dry weight and 101 +/- 7 microM/g dry weight, respectively. During reperfusion, a further elevation was found in retinal Na in both the normotensive and hypertensive groups. Probably, because of the ischaemia-induced inhibition of Na-K-ATPase, retinal K loss was detected after ischaemia and reperfusion, respectively. An accumulation of retinal Ca was measured after ischaemia and reperfusion in the normotensive and spontaneously hypertensive groups. Both free radical scavengers significantly reduced the maldistribution of ions induced by ischaemia and reperfusion, but the effectiveness of drugs was more evident in normotensive than hypertensive groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Oxidative stress in diabetic retina.

The authors describe the alterations usually associated with diabetic retinopathy. They concern the classical thickening of the basal membrane of retinal capillaries and the associated modification of retinal vessel permeability. These alterations correspond to the blood-retinal barrier disruption. The authors then discuss the participation of oxygenated free radicals in the pathogenesis of diabetic retinopathy. They report several experimental studies establishing such a participation and finally describe their own results obtained on a model of retinas isolated from alloxan-induced diabetic rats. After one month of evolution, the electroretinograms (ERG) recorded on isolated retinas from diabetic rats had an amplitude about 20% lower than the controls, whereas after two months of diabetes, this decrease was about 60%. Under these conditions, the authors tested the protective properties of Ginkgo biloba extract (EGb 761) on their model. They observed that in EGb-treated animals (100 mg/kg/day), the ERG had a significantly (p less than 0.001) greater amplitude than untreated animals after two months of diabetes evolution. In conclusion, the authors discuss the possible utilization of a free radical scavenger, such as EGb 761, in the prevention of the retinal impairment in diabetes.

Animals↗
PubMed1992

Light and lithium effects in the rat retina: modification by the PAF antagonist BN 52021.

We tested the effect of an antagonist of platelet-activating factor (PAF), BN 52021, on both acute light-induced and light plus lithium-induced rod outer segment (ROS) lesions. Rats were fed lithium carbonate (2.6 g/kg chow) for 3 weeks. Half of the lithium-treated rats received BN 52021 (25 mg/kg) via gastric intubation prior to light exposure. Control and treated rats were exposed to 400-450 lux (measured at the eye level of the rats) of diffuse, white fluorescent light for 30 min, followed by 2 h of darkness and then decapitated. The eyes were removed and prepared for light and electron microscopic observation. The structural alterations of ROS were quantified from electron micrographs using a multifunctional computer image-analysis system. Our data show a significant reduction of ROS lesions by BN 52021, and this is most pronounced in light plus lithium-treated rats. Furthermore, in confirmation of previous studies, chronic lithium treatment significantly augmented light-elicited phagosome numbers, and BN 52021 reduced this effect. Our findings thus suggest that light and lithium may act via PAF responses in the rat retina.

Analysis of Variance↗
PubMed1992

Ischaemia- and reperfusion-induced Na+, K+, Ca2+ and Mg2+ shifts in rat retina: effects of two free radical scavengers, SOD and EGB 761.

Using Sprague-Dawley rats with transient (90-min) regional ischaemia induced by retinal artery occlusion in the eye, we have shown that superoxide dismutase (SOD) and EGB 761 (IPSEN, France), two free radical scavengers, can dramatically reduce the reperfusion-induced sodium and calcium gains, and potassium loss in retinal tissue. Investigating whether this was a 'direct' protective effect, operating during reperfusion, or an 'indirect' effect arising from the action of SOD or EBG 761 on the tissue during ischaemia. SOD (15,000 U kg-1) and EGB 761 (100 mg kg-1) were added to the rats at the moment of reperfusion (after an ischaemic insult). Eyes were subjected to 90 min ischaemia followed by 4 and 24 hr of reperfusion, respectively. In the drug-free control group, 90 min of ischaemia resulted in an accumulation of retinal sodium (2-fold) and calcium (3-fold), and a loss of cell potassium (by 40%) and magnesium (by 40%). During the first 4 hr of reperfusion the ionic imbalance was unchanged, while after 24 hrs of reperfusion a normalization was observed and the ion content of the retina almost returned to their preischaemic values. SOD and EGB 761 treatment significantly reduced the reperfusion-induced ionic imbalance (magnesium was an exception) and improved the recovery of retinal ion contents. Our results indicate that the elimination of oxygen radicals by free radical scavengers may reduce the reperfusion-induced ionic imbalance and improve the ionic homeostasis in the injured retinal cells.

Animals↗
PubMed1992

Modification of reperfusion-induced ionic imbalance by free radical scavengers in spontaneously hypertensive rat retina.

We studied the effects of free radical scavengers, superoxide dismutase (SOD), vitamin E, and EGB 761, on ion shifts (Na+, K+, and Ca2+) induced by ischemia reperfusion in rat retina obtained from spontaneously hypertensive rats. Eyes were subjected to 90 min of retinal ischemia followed by 24 h of reperfusion. Two basic protocols were used: (1) chronic application, in which rats received SOD (7500, 15,000, and 30,000 U/kg, i.v.), vitamin E (50, 100, and 200 mg/kg, i.v.), and EGB 671 (50, 100, and 200 mg/kg, orally) for 10 d, respectively; and (2) acute administration, in which 7500, 15,000, and 30,000 U/kg of SOD, 50, 100, and 200 mg/kg of vitamin E, and 50, 100, and 200 mg/kg of EGB 761 were administered after an ischemic episode, at the onset of reperfusion, respectively. In the drug-free control group, 90 min ischemia followed by 24 h of reperfusion resulted in an accumulation of retinal sodium and calcium from their nonischemic control values of 76 +/- 4 and 3.2 +/- 0.1 mumol/g dry weight to 112 +/- 6 (p < .001) and 6.2 (p < .001) mumol/g dry weight, respectively. Tissue potassium loss was also observed in this model of retinal ischemia reperfusion, and after 90 min ischemia followed by 24 h of reperfusion potassium content was significantly reduced from its nonischemic control value of 266 +/- 5 to 207 +/- 6 (p < .001) mumol/g dry weight. The chronic administration of SOD, vitamin E, and EGB 761 dose dependently reduced the reperfusion-induced ionic imbalance and improved the recovery of retinal ion contents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of Gingko biloba extract (EGb 761) on chloroquine induced retinal alterations.

Electroretinography was used to investigate the preventive action of Ginkgo biloba extract (EGb 761) in experimental chloroquine-induced retinopathy in rats. EGb 761 contains flavones and anthocyanosides known for their oxygenated radical scavenging properties. Chronic administration of chloroquine (20 days) caused an overall lengthening of the duration of the ERG b-wave, together with delayed peaking. These anomalies became more marked with increased duration of treatment. In rats treated simultaneously with chloroquine and EGb 761 no such modification of the electroretinogram (ERG) was observed. These results suggest that retinal toxicity may be related to a localized inflammation releasing oxygenated free radicals and/or PAF. EGb 761 may thus afford a useful preventive treatment for chloroquine-induced retinopathy, and generally for xenobiotic retinotoxicities.

Animals↗