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Biomedical subjects

C Remé

Publications and source records attributed to C Remé.

At least 19 recordsLinked to original sources
PubMed2001

Protective effect of halothane anesthesia on retinal light damage: inhibition of metabolic rhodopsin regeneration.

PURPOSE: To determine whether the volatile anesthetic halothane protects against light-induced photoreceptor degeneration in the rodent retina. METHODS: Albino mice and rats were anesthetized with halothane and exposed to high levels of white or blue light. Nonanesthetized animals served as controls. Retinal morphology was assessed by light microscopy, and apoptosis of photoreceptor cells was verified by detection of fragmented genomic DNA and in situ staining of apoptotic nuclei (TUNEL assay). Rhodopsin regeneration after bleaching was determined by measuring rhodopsin levels in retinas of mice or rats at different time points in darkness. RESULTS: Halothane anesthesia reversibly inhibited metabolic rhodopsin regeneration and thus prevented rhodopsin from absorbing high numbers of photons during light exposure. Consequently, photoreceptors of mice and rats anesthetized with halothane were completely protected against degeneration induced by white light. In remarkable contrast, however, halothane anesthesia did not protect against blue-light-induced photoreceptor cell death. CONCLUSIONS: After the initial bleach, halothane impeded photon absorption by rhodopsin by inhibiting metabolic rhodopsin regeneration. Apparently, the rhodopsin-mediated uptake of the critical number of photons to initiate white light-induced retinal degeneration was prevented. In contrast, halothane did not protect the retina against blue light. Blue light can efficiently restore functional rhodopsin from bleaching intermediates through a process termed photoreversal of bleaching. This process does not depend on the visual cycle via the pigment epithelium but nevertheless enables rhodopsin molecules to absorb the critical number of photons required to induce retinal degeneration.

Anesthesia, Inhalation↗
PubMed2001

Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching.

PURPOSE: Acute white-light damage to rods depends on the amount of rhodopsin available for bleaching during light exposure. Bleached rhodopsin is metabolically regenerated through the visual cycle involving the pigment epithelium, or photochemically by deep blue light through photoreversal of bleaching. Because photoreversal is faster than metabolic regeneration of rhodopsin by several orders of magnitude, the photon catch capacity of the retina is significantly augmented during blue-light illumination, which may explain the greater susceptibility of the retina to blue light than to green light. However, blue light can also affect function of several blue-light-absorbing enzymes that may lead to the induction of retinal damage. Therefore, this study was conducted to test whether rhodopsin and its bleaching intermediates play a role in blue-light-induced retinal degeneration. METHODS: Eyes of anesthetized rats and mice that did or did not contain rhodopsin were exposed to green (550 +/- 10 nm) or deep blue (403 +/- 10 nm) light for up to 2 hours. Rats with nearly rhodopsinless retinas were obtained by bleaching rhodopsin in animals with inhibited metabolic rhodopsin regeneration-that is, under halothane anesthesia. In addition, Rpe65(-/-) mice that are completely without rhodopsin were used to test the susceptibility to blue-light damage of a rodent retina completely devoid of the visual pigment. Effects of illumination on photoreceptor morphology were assessed 24 hours or 10 days thereafter by morphologic and biochemical methods. RESULTS: Exposure to blue light resulted in severe retinal damage and activation of the transcription factor AP-1 in rats. In contrast, green light had no effect. When rhodopsin was almost completely bleached by short-term green-light exposure while metabolic regeneration (but not photoreversal) was prevented by halothane anesthesia, blue-light exposure induced distinct lesions in rat retinas. When both metabolic rhodopsin regeneration and photoreversal of bleaching were almost completely inhibited, blue-light exposure caused only very moderate lesions. When mice without rhodopsin were exposed to blue light, no damage occurred, in contrast to wild-type control mice. CONCLUSIONS: Short time exposure to blue light has deleterious effects on retinal morphology. Because damage was observed only in the presence of the visual pigment, blue-light-induced retinal degeneration is rhodopsin mediated. Absorption of blue light by other proteins is not sufficient to induce light damage. Photoreversal of bleaching, which occurs only in blue but not in green light, increases the photon-catch capacity of the retina and may thus account for the difference in the damage potential between blue and green light.

Animals↗
PubMed2000

Age-related macular degeneration. The lipofusion component N-retinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells.

10-20% of individuals over the age of 65 suffer from age-related macular degeneration (AMD), the leading cause of severe visual impairment in humans living in developed countries. The pathogenesis of this complex disease is poorly understood, and no efficient therapy or prevention exists to date. A precondition for AMD appears to be the accumulation of the age pigment lipofuscin in lysosomes of retinal pigment epithelial (RPE) cells. In AMD, these cells seem to die by apoptosis with subsequent death of photoreceptor cells, and light may accelerate the disease process. Intracellular factors leading to cell death are not known. Here we show that the lipophilic cation N-retinyl-N-retinylidene ethanolamine (A2E), a lipofuscin component, induces apoptosis in RPE and other cells at concentrations found in human retina. Apoptosis is accompanied by the appearance of the proapoptotic proteins cytochrome c and apoptosis-inducing factor in the cytoplasm and the nucleus. Biochemical examinations show that A2E specifically targets cytochrome oxidase (COX). With both isolated mitochondria and purified COX, A2E inhibits oxygen consumption synergistically with light. Inhibition is reversed by the addition of cytochrome c or cardiolipin, a negatively charged phospholipid that facilitates the binding of cytochrome c to membranes. Succinate dehydrogenase activity is not altered by A2E. We suggest that A2E can act as a proapoptotic molecule via a mitochondria-related mechanism, possibly through site-specific targeting of this cation to COX. Loss of RPE cell viability through inhibition of mitochondrial function might constitute a pivotal step toward the progressive degeneration of the central retina.

Aging↗
PubMed2000

Membrane formation in the chamber angle after failure of argon laser trabeculoplasty: analysis of risk factors.

AIM: Membrane formation in the chamber angle induced by argon laser trabeculoplasty (ALT) can be a cause of treatment failure. Identification of risk factors for membrane formation was the primary aim of this retrospective study. METHODS: Semithin sections of trabeculectomy specimens obtained in a 2 year period were examined by light microscopy. 122 eyes which were treated with one or more ALTs before trabeculectomy were identified. In 46 eyes, a sufficient amount of trabecular meshwork was obtained to permit morphological analysis. RESULTS: Eyes treated with ALT had a significantly higher incidence of membrane formation (p=0.001). In 23/46 specimens a cellular and collagenous membrane was observed covering the entire trabecular meshwork. In 14/23 specimens (61%), this membrane was readily visible at low power magnification (x40). Comparison of these eyes with those without membrane formation revealed a significant difference in the number of ALTs (mean 2.07 (SD 0.73) v 1.48 (0.59); p=0.026) and in preoperative IOP (32.0 (9. 7) v 26.2 (8.4) mm Hg; p=0.04). CONCLUSIONS: Membrane formation in the chamber angle is a frequent cause of ALT failure. The major risk factor is the number of ALTs performed.

Aged↗
PubMed1996

Light damage revisited: converging evidence, diverging views?

Are observations on ultraviolet (UV)- and visible light-induced ocular changes in animals relevant for human pathology? Different conclusions are drawn by different groups, depending on their perspective: while in the epidemiologist's view the evidence for those lesions is mostly limited or insufficient, laboratory scientists continually extend observations on radiation damage in animals. Consequently, there are diverging views on the necessity and specifications for eye protection. In this review, problems of epidemiological surveys and observations in humans and animal studies are discussed, and natural and artificial protection of the eye is outlined. The human and animal eye has an inherent potential for photochemical lesions due to chromophores including the visual pigments that are present at birth. Lifelong light exposure gives rise to additional absorbing molecules. With decreasing wavelengths of the electromagnetic spectrum the number of absorbing molecules rises; therefore, the likelihood of a photochemical reaction grows. As the spectral energy is augmented, more damage will occur. In our view, the knowledge gained from laboratory studies is a significant component of the total evidence from different fields-epidemiology, clinical observations, model studies and theoretical calculations-that UV radiation and short-wavelength visible light can cause acute and chronic changes in ocular structures. Such changes may comprise irreversible damage. Following recently issued recommendations of the major visual health organizations in the United States, protection against UV and blue light should be incorporated into the spectrum of safety considerations for sunglasses.

Absorption↗
PubMed1996

[Risk factors for development of argon laser trabeculoplasty failure producing membrane in the chamber angle].

INTRODUCTION: The major cause of ALT failure is membrane formation in the chamber angle. The aim of this retrospective study was to identify possible risk factors. MATERIAL AND METHODS: We studied sections from the surgical specimens from all trabeculectomies at our department within 2 years. We identified 122 eyes with at least one preoperative ALT. In 46 specimens enough trabecular meshwork for morphological analysis was present. RESULTS: Half of the patients showed a membrane covering the trabecular meshwork. In 14 of 23 eyes we could see this membrane even at low-power magnification (40 x). Various possible risk factors were evaluated, but none showed a significant correlation. When we compared only these eyes with membranes visible at low-power magnification with eyes without, however, we found a significant difference in the number of ALTs (mean +/- SD 2.07 +/- 0.73 vs 1.48 +/- 0.59; P = 0.026) and preoperative intraocular pressure (32.0 +/- 9.7 mmHg vs 26.2 +/- 8.4 mmHg; P = 0.04). CONCLUSION: We found no distinct risk factor for membrane formation, but it becomes more frequent with every additional laser treatment.

Adult↗
PubMed1994

Light-evoked arachidonic acid release in the retina: illuminance/duration dependence and the effects of quinacrine, mellitin and lithium. Light-evoked arachidonic acid release.

Arachidonic acid (AA) is the precursor molecule of a variety of cellular lipid mediators that interact with retinal physiology. In this study, we investigated the time- and illuminance-dependence of the release of AA in the rat retina in vitro in control and lithium-pretreated rats. We also studied the effects of the specific phospholipase A2 (PLA2) inhibitor quinacrine and the specific PLA2 stimulator mellitin on the release of AA. Isolated rat retinas were labelled with 3H-AA for 90 min in vitro in darkness and the incorporation of AA into retinal phospholipids was monitored by thin-layer chromatography. The release of 3H-AA in the incubation medium was determined under different illuminance and timing conditions, with the addition of quinacrine and mellitin, and after pretreatment of the animals with lithium. Light exposure of the prelabelled isolated retinas evoked up to a two-fold increase in AA release compared with retinas incubated for the same time in darkness. The AA release was dependent on illuminance time (10,000 1x white fluorescent light for 0.25, 2, 5 and 10 min) and illuminance level (0, 100, 1000, 5000, and 10,000 1x for 10 min). Complete rhodopsin bleaching occurred after 2 min at 10,000 1x. Quinacrine significantly suppressed the light-elicited AA release whereas mellitin increased the release of AA in dark-adapted and light-exposed retinas. Lithium pretreatment, which is known to potentiate light-evoked rod outer segment disruptions, significantly augmented the light-evoked AA release. Our results confirm a light-stimulated release of AA in the retina.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
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↗
PubMed1990

Effect of in vivo modulation of membrane docosahexaenoic acid levels on the dopamine-dependent adenylate cyclase activity in the rat retina.

We have studied the effect of a dietary deprivation of n-3 fatty acids on the activity of the dopamine (DA)-dependent adenylate cyclase in the rat retina. Experiments were conducted in 6-month-old rats raised on semipurified diets containing either safflower oil (n-3 deficient diet) or soybean oil (control diet). The levels of docosahexaenoic acid [22:6 (n-3)] in retinal phospholipids were significantly decreased in n-3 deficient rats (35-42% of control levels). This was compensated by a rise in 22:5 (n-6), the total content of polyunsaturated fatty acids (PUFA) remaining approximately constant. Adenylate cyclase activity was measured in retinal membrane preparations from dark-adapted or light-exposed rats. The enzyme activity was stimulated by DA and SKF 38393 in a light-dependent fashion. The activation was lower in rats exposed to light than in dark-adapted animals, suggesting a down-regulation of the D1 DA receptors by light. The activation by guanine nucleotides and forskolin was also decreased in light-exposed rats. There was no significant effect of the dietary regimen on the various adenylate cyclase activities and their response to light. Furthermore, the guanine nucleotide- and DA-dependent adenylate cyclase activities of retinal membranes were found to be relatively resistant to changes in membrane fluidity induced in vitro by benzyl alcohol. The results indicate that in the absence of changes in total PUFA content, a decreased ratio of n-3 to n-6 fatty acids in membrane phospholipids does not significantly affect the properties of adenylate cyclase in the rat retina.

Adenylyl Cyclases↗
PubMed1988

Light-induced phosphoinositide degradation and light-induced structural alterations in the rat retina are enhanced after chronic lithium treatment.

In the rat retina, light-induced break down of polyphosphoinositides and structural alterations of photoreceptor outer segment disk-membranes were enhanced by chronic lithium treatment at doses equivalent to therapeutic levels in humans. Furthermore, the recovery of phosphoinositide baseline levels after light exposure was delayed in lithium treated retinas. Light and lithium may thus affect phospholipid membranes in the retina. Initial processes in the pathogenesis of light damage in the retina are largely unknown to date. The hydrolysis of polyphosphoinositides may possibly constitute such an initial event.

Animals↗
PubMed1988

[Lithium-induced lesions in the rat retina--potentiation by light].

The treatment of manic-depressive patients with lithium salts is a widespread procedure. Ocular side effects of this therapy comprise changes in electrophysiological and psychophysical parameters. Photochemical damage to the human and animal retina is a widely recognized and investigated phenomenon. The present paper describes lithium-induced changes in the albino rat retina on a morphological and biochemical level that are significantly enhanced by acute light exposure in an intensity-dependent manner. Preliminary biochemical data reveal an increase in phosphatidylinositol metabolites. As a clinical consequence of the study the authors advocate careful ophthalmological examination of chronically lithium-treated patients, especially those suffering from retinal degeneration or who are exposed to light of higher than normal intensity.

Animals↗
PubMed1988

Morphology and time-course of defined photochemical lesions in the rabbit retina.

The present study demonstrates an experimental set-up to study light injury with defined parameters including retinal irradiance levels and spectral composition of the damaging light. The time-course of acute morphological changes at constant light intensity and increasing exposure durations (from 5-30 minutes) was evaluated, the wavelength of the damaging light being 400-550 nm. Pigment epithelial lesions appeared already after 5 minutes, and rod outer segment membrane disruptions after 15-20 minutes of light exposure. Striking was the observation of disruption and vesiculation of disk membranes at the base of rod outer segments. This "clear zone" was consistently observed beginning after twenty minutes of light exposure. The comparison of morphological changes in pigmented and albinotic eyes revealed no essential differences. This result confirms the observations of other laboratories that pigment epithelial melanin neither protects against nor promotes light damage to a significant extent. Long-term changes after light exposure revealed pigment epithelial lesions and rod outer segment disruptions, followed by macrophage invasion and pigment epithelial proliferation with subsequent loss of photoreceptor cells.

Albinism↗
PubMed1986

Circadian rhythm in the light response of rat retinal disk-shedding and autophagy.

Under a light-dark cycle, disk-shedding and autophagy in the rat retina peak in the early and mid light phase, respectively. Under constant conditions, disk-shedding and autophagy responses after light stimulation were elicited at different time points of a 24-h cycle. The greatest magnitude of response occurred in the late dark and early light phase. Thus there is a circadian variation of the light response of important metabolic parameters in the mammalian retina. Inhibition of dopamine synthesis during the early light phase caused a significant dampening of the light responses of both disk-shedding and autophagy.

Animals↗
PubMed1986

[Visual cells of the vertebrate retina. Renewal processes, rhythms, and light].

Vertebrate visual cells represent a system in an extraordinarily dynamic state. Major parts of the photoreceptors are continually degraded and resynthesized, thus, the cell's morphological and functional integrity is maintained. Some components of visual cell renewal processes follow an endogenous, circadian rhythm driven by an ocular oscillator. Regulative mechanisms of these circadian rhythms may comprise interactions between the neurohormone melatonin and the putative retinal neurotransmitter and neuromodulator dopamine.

Animals↗