Light Exposure Levels Research Articles

Photodynamic effects induced by meso-tris(pentafluorophenyl)corrole and its cyclodextrin conjugates on cytoskeletal components of HeLa cells.

The aim of this work was to synthesize new corrole β-cyclodextrin conjugates βCD1 (with one β-cyclodextrin moiety) and βCD2 (with two β-cyclodextrin moieties) from 5,10,15-tris(pentafluorophenyl)corrole (TPFC) and to test invitro the efficacy of these compounds towards tumoral HeLa cells. No dark cytotoxicity was observed for TPFC and βCD1 at the concentration used for PDT cell treatment, even during long incubation periods (24h). Fluorescence microscopy showed that TPFC and βCD1 accumulate in HeLa cells at lysosomes and in the Golgi apparatus, respectively. The cell survival after the PDT treatment with visible light was dependent on light exposure level and compound concentration. βCD1 was able to penetrate efficiently in the cytoplasm of the HeLa cells. In particular, we have analyzed the photodynamic effect of the corrole derivatives on the microtubules of HeLa cells and the morphological alterations on the mitotic spindle. TPFC and βCD1 caused photocytotoxicity in tumoral HeLa cells and induced a rapid metaphase blockage of cells that also showed clearly altered configurations of the mitotic spindle. The results showed that TPFC has the highest photosensitizing efficiency on tumoral cells.

Rapid measurement of molecular transport and interaction inside living cells using single plane illumination.

The ability to measure biomolecular dynamics within cells and tissues is very important to understand fundamental physiological processes including cell adhesion, signalling, movement, division or metabolism. Usually, such information is obtained using particle tracking methods or single point fluctuation spectroscopy. We show that image mean square displacement analysis, applied to single plane illumination microscopy data, is a faster and more efficient way of unravelling rapid, three-dimensional molecular transport and interaction within living cells. From a stack of camera images recorded in seconds, the type of dynamics such as free diffusion, flow or binding can be identified and quantified without being limited by current camera frame rates. Also, light exposure levels are very low and the image mean square displacement method does not require calibration of the microscope point spread function. To demonstrate the advantages of our approach, we quantified the dynamics of several different proteins in the cyto- and nucleoplasm of living cells. For example, from a single measurement, we were able to determine the diffusion coefficient of free clathrin molecules as well as the transport velocity of clathrin-coated vesicles involved in endocytosis. Used in conjunction with dual view detection, we further show how protein-protein interactions can be quantified.

In vivo and in vitro evaluation of the cytotoxic effects of Photosan-loaded hollow silica nanoparticles on liver cancer.

This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions (p < 0.05). Flow cytometry data demonstrated that laser-induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II (p < 0.05). Activated caspase-3 and caspase-9 levels were significantly higher in cells treated with Photosan-II loaded in silica nanoparticles than free Photosan-II (p < 0.05). Accordingly, treatment with nanoscale photosensitizers resulted in improved outcomes (tumor volume) in a mouse model of liver cancer, in comparison with conventional photosensitizers. Hollow silica nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro.

Degradation of kresoxim-methyl in soil: Impact of varying moisture, organic matter, soil sterilization, soil type, light and atmospheric CO2 level

In the present investigation, persistence of kresoxim-methyl (a broad spectrum strobilurin fungicide) was studied in two different soil types of India namely Inceptisol and Ultisol. Results revealed that kresoxim-methyl readily form acid metabolite in soil. Therefore, residues of kresoxim-methyl were quantified on the basis of parent molecule alone and sum total of kresoxim-methyl and its acid metabolite. Among the two soil types, kresoxim-methyl and total residues dissipated at a faster rate in Inceptisol (T1/2 0.9 and 33.8d) than in Ultisol (T1/2 1.5 and 43.6d). Faster dissipation of kresoxim-methyl and total residues was observed in submerged soil conditions (T1/2 0.5 and 5.2d) followed by field capacity (T1/2 0.9 and 33.8d) and air dry (T1/2 2.3 and 51.0d) conditions. Residues also dissipated faster in 5% sludge amended soil (T1/2 0.7 and 21.1d) and on Xenon-light exposure (T1/2 0.5 and 8.0d). Total residues of kresoxim-methyl dissipated at a faster rate under elevated CO2 condition (∼550μLL−1) than ambient condition (∼385μLL−1). The study suggests that kresoxim-methyl alone has low persistence in soil. Because of the slow dissipation of acid metabolite, the total residues (kresoxim-methyl+acid metabolite) persist for a longer period in soil. Statistical analysis using SAS 9.3 software and Duncan’s Multiple Range Test (DMRT) revealed the significant effect of moisture regime, organic matter, microbial population, soil type, light exposure and atmospheric CO2 level on the dissipation of kresoxim-methyl from soil (at 95% confidence level p<0.0001).

Light Exposure and Physical Activity in Myopic and Emmetropic Children

To objectively assess daily light exposure and physical activity levels in myopic and emmetropic children. One hundred two children (41 myopes and 61 emmetropes) aged 10 to 15 years old had simultaneous objective measures of ambient light exposure and physical activity collected over a 2-week period during school term, using a wrist-worn actigraphy device (Actiwatch 2). Measures of visible light illuminance and physical activity were captured every 30 seconds, 24 hours a day over this period. Mean hourly light exposure and physical activity for weekdays and weekends were examined. To ensure that seasonal variations did not confound comparisons, the light and activity data of the 41 myopes was compared with 41 age- and gender-matched emmetropes who wore the Actiwatch over the same 2-week period. Mean light exposure and physical activity for all 101 children with valid data exhibited significant changes with time of day and day of the week (p < 0.0001). On average, greater daily light exposure occurred on weekends compared to weekdays (p < 0.05), and greater physical activity occurred on weekdays compared to weekends (p < 0.01). Myopic children (n = 41, mean daily light exposure 915 ± 519 lx) exhibited significantly lower average light exposure compared to 41 age- and gender-matched emmetropic children (1272 ± 625 lx, p < 0.01). The amount of daily time spent in bright light conditions (>1000 lx) was also significantly greater in emmetropes (127 ± 51 minutes) compared to myopes (91 ± 44 minutes, p < 0.001). No significant differences were found between the average daily physical activity levels of myopes and emmetropes (p > 0.05). Myopic children exhibit significantly lower daily light exposure, but no significant difference in physical activity compared to emmetropic children. This suggests the important factor involved in documented associations between myopia and outdoor activity is likely exposure to bright outdoor light rather than greater physical activity.

Daily activity and light exposure levels for five species of lemurs at the duke lemur center

Light is the primary synchronizer of all biological rhythms, yet little is known about the role of the 24-hour luminous environment on nonhuman primate circadian patterns, making it difficult to understand the photic niche of the ancestral primate. Here we present the first data on proximate light-dark exposure and activity-rest patterns in free-ranging nonhuman primates. Four individuals each of five species of lemurs at the Duke Lemur Center (Eulemur mongoz, Lemur catta, Propithecus coquereli, Varecia rubra, and Varecia variegata variegata) were fitted with a Daysimeter-D pendant that contained light and accelerometer sensors. Our results reveal common as well as species-specific light exposure and behavior patterns. As expected, all five species were more active between sunrise and sunset. All five species demonstrated an anticipatory increase in their pre-sunrise activity that peaked at sunrise with all but V. rubra showing a reduction within an hour. All five species reduced activity during mid-day. Four of the five stayed active after sunset, but P. coquereli began reducing their activity about 2 hours before sunset. Other subtle differences in the recorded light exposure and activity patterns suggest species-specific photic niches and behaviors. The eventual application of the Daysimeter-D in the wild may help to better understand the adaptive evolution of ancestral primates.

Hospital lighting and its association with sleep, mood and pain in medical inpatients

To describe light exposure, sleep-wake patterns, mood, pain and their relationships in adult medical inpatients. The hospital environment may contribute to patient discomfort by providing a lighting structure that interferes with circadian rhythmicity, sleep, mood and pain. A descriptive correlational design was used in this preliminary study. Between May 2011-April 2012, data were collected from a convenience sample of 23 women and 17 men admitted to a large academically affiliated hospital in the United States. Over 72hours, light exposure and sleep-wake patterns were continuously measured with wrist actigraph/light meters for each participant. Mood was measured daily using the Profile Of Mood States Brief™ Form. Subjective pain scores were abstracted from medical records. Light exposure levels were low: mean daytime light intensity was 104·80 lux. Sleep time was fragmented and low: mean 236·35minutes of sleep/night. Intra-daily stability scores indicated little sleep-wake synchronization with light. Fatigue and total mood disturbance scores were high and inversely associated with light. Pain levels were also high and positively associated with fatigue, but not directly with light exposure. Low light exposure significantly predicted fatigue and total mood disturbance. Medical inpatients were exposed to light levels insufficient for circadian entrainment. Nevertheless, higher light exposure was associated with less fatigue and lower total mood disturbance in participants with pain, suggesting the need for further investigation to determine if manipulating light exposure for medical inpatients would be beneficial in affecting sleep-wake disturbances, mood and pain.

Determining the Methoxypyrazine Biosynthesis Variables Affected by Light Exposure and Crop Level in Cabernet Sauvignon

Methoxypyrazines are sensorially potent volatile compounds responsible for herbaceous/vegetal attributes in wines made from certain grape varieties. The biosynthesis of these compounds in grape berries is known to occur via a pathway that involves the methylation of hydroxypyrazine intermediates. Certain viticultural management regimes can be used to alter methoxypyrazine concentrations in fruit of those varieties that have the genetic capability of producing them. This study explored the effect of light exposure and crop level on 3-isobutyl-2-methoxypyrazine (IBMP) concentrations in Cabernet Sauvignon fruit to better understand the effect of these variables on the concentration of the precursor 3-isobutyl-2-hydroxypyrazine (IBHP) and the expression of a methyltransferase gene (VvOMT3) responsible for the final step in methoxypyrazine biosynthesis. Light was found to reduce the expression of VvOMT3 and the concentration of IBHP, suggesting that a combination of these factors reduces IBMP concentration when fruit has greater light exposure. In contrast, reducing the crop level of vines to less than half of that of controls did not have a significant effect on IBHP concentration or VvOMT3 expression, despite the treatment causing a significant increase in IBMP concentration. IBMP appears to be synthesized in the flesh of the berry which suggests differences in berry size may explain the crop level effect on IBMP concentrations.

Performance enhancement of fullerene-based solar cells by light processing

A key challenge to the commercialization of organic bulk heterojunction solar cells is the achievement of morphological stability, particularly under thermal stress conditions. Here we show that a low-level light exposure processing step during fabrication of blend polymer:PC60BM solar cells can result in a 10-fold increase in device thermal stability and, under certain conditions, enhanced device performance. The enhanced stability is linked to the light-induced oligomerization of PC60BM that effectively hinders their diffusion and crystallization in the blend. We thus suggest that light processing may be a promising, general and cost-effective strategy to optimize fullerene-based solar cell performance. The low level of light exposure required suggests not only that this may be an easily implementable strategy to enhance performance, but also that light-induced PC60BM oligomerization may have inadvertently influenced previous studies of organic solar cell device behaviour.

361 Circadian Rhythm Disruption in Emergency Medicine Residents

361 Circadian Rhythm Disruption in Emergency Medicine Residents

Performance of Pacific white shrimp Litopenaeus vannamei raised in biofloc systems with varying levels of light exposure

Most research on biofloc systems has been performed in greenhouses with abundant natural light. The functionality of these systems in an environment devoid of light remains poorly understood, especially with regard to growth and survival of reared animals. This study evaluated the performance of Litopenaeus vannamei reared in a biofloc system with varying levels of light. Treatments were 24h with light (24WL), 12h with light/12h without light (12WL/12WOL), and 24h without light (24WOL), each with four replicate tanks. The 24WL and 12WL/12WOL treatments were supplied with light intensity of 10000lx. Shrimp with mean±SD initial weight of 3.3±0.1g were reared in 850L-tanks at a density of 300shrimpm−3. With the exception of nitrate, TSS, VSS and chlorophyll a, there were no significant differences (P>0.05) in water quality parameters among treatments. Nitrate was higher (P<0.05) in 24WOL treatment than in 24WL but neither was significantly different from 12WL/12WOL. TSS and VSS were higher (P<0.05) in 24WL treatment than 24WOL, but were not significantly different from 12WL/12WOL treatment. Chlorophyll a was higher (P<0.05) in 24WL treatment than in 12WL/12WOL and 24WOL treatments. There were no significant differences (P>0.05) in shrimp survival and feed conversion ratios among the treatments. However, shrimp in 24WL treatment grew at a significantly greater rate and reached a significantly greater final weight than shrimp in 24WOL treatment (P<0.05), but neither was significantly different from 12WL/12WOL. The results demonstrate that shrimp production was higher in the treatment that were exposed to light; however Pacific white shrimp can be raised in total absence of light with acceptable performance.

Effect of Reduced Illumination on Insomnia in Office Workers

We evaluated the possible effects of reduced illumination in the workplace on insomnia among office workers. Seventy-two office workers answered the Athens Insomnia Scale (AIS) in July 2009 (under ordinary illumination, 01 conditions) and July 2010 (under reduced illumination, Rl conditions). The workers were divided into three groups, indoor workers (IWs), semi-outdoor workers (SWs) and outdoor workers (OWs), according to the frequency of working outside of the office because a worker with a high frequency of working outside of the office might rarely be exposed to the lighting condition within an office. The first five items of the AIS (AIS-5) were used to assess sleep difficulties, and the last three items (AIS-3) assessed next-day consequences of sleep or daytime symptoms, which often result from insomnia and/or sleep disorders. Illuminance levels at a height of 1,100 mm from the floor under the Rl conditions (550-490 lux) were significantly lower than under the Ol conditions (750-700 lux). The AIS-5 score of the IWs was significantly increased under the Rl conditions compared with the Ol conditions. There was no difference in AIS-3 scores between conditions for any group. Indoor workers hardly went outside of the office and were exposed only to office light during the daytime. Thus, the underexposure to light could have had an impact on insomnia in those individuals. A novel lighting environment is required to optimize work-related levels of light exposure.

Comparisons of three practical field devices used to measure personal light exposures and activity levels

This paper documents the spectral and spatial performance characteristics of two new versions of the Daysimeter, devices developed and calibrated by the Lighting Research Center to measure and record personal circadian light exposure and activity levels, and compares them to those of the Actiwatch Spectrum (Philips Healthcare). Photometric errors from the Daysimeters and the Actiwatch Spectrum were also determined for various types of light sources. The Daysimeters had better photometric performance than the Actiwatch Spectrum. To assess differences associated with measuring light and activity levels at different locations on the body, older adults wore four Daysimeters and an Actiwatch Spectrum for five consecutive days. Wearing the Daysimeter or Actiwatch Spectrum on the wrist compromises accurate light measurements relative to locating a calibrated photosensor at the plane of the cornea.

Glycophthalocyanines as Photosensitizers for Triggering Mitotic Catastrophe and Apoptosis in Cancer Cells

Photodynamic therapy (PDT) is a treatment modality for different forms of cancer based on the combination of light, molecular oxygen, and a photosensitizer (PS) compound. When activated by light, the PS generates reactive oxygen species leading to tumor destruction. Phthalocyanines are compounds that have already shown to be efficient PSs for PDT. Several examples of carbohydrate substituted phthalocyanines have been reported, assuming that the presence of carbohydrate moieties could improve their tumor selectivity. This work describes the photoeffects of symmetric and asymmetric phthalocyanines with D-galactose (so-called GPh1, GPh2, and GPh3) on HeLa carcinoma cells and their involvement in cell death. Photophysical properties and in vitro photodynamic activities for the compounds considered revealed that the asymmetric glycophthalocyanine GPh3 is very efficient and selective, producing higher photocytotoxicity on cancer cells than in nonmalignat HaCaT. The cell toxiticy after PDT treatment was dependent upon light exposure level and GPh3 concentration. GPh3 causes cell cycle arrest at the metaphase stage leading to multiple spindle poles, mitotic catastrophe, followed by apoptosis in cancer cells. These effects were partially negated by the pancaspase inhibitor Z-VAD-FMK. Together, these results indicate that GPh3 is an excellent candidate drug for PDT, able to induce selective tumor cell death.

Relationship of Chronotype to Sleep, Light Exposure, and Work-Related Fatigue in Student Workers

Students who work during the school year face the potential of sleep deprivation and its effects, since they have to juggle between school and work responsibilities along with social life. This may leave them with less time left for sleep than their nonworking counterparts. Chronotype is a factor that may exert an influence on the sleep of student workers. Also, light and social zeitgebers may have an impact on the sleep-related problems of this population. This study aimed to document sleep, light exposure patterns, social rhythms, and work-related fatigue of student workers aged 19–21 yrs and explore possible associations with chronotype. A total of 88 student workers (mean ± SD: 20.18 ± .44 yrs of age; 36 males/52 females) wore an actigraph (Actiwatch-L; Mini-Mitter/Respironics,Bend, OR) and filled out the Social Rhythm Metric for two consecutive weeks during the school year. Also, they completed the Morningness-Eveningness Questionnaire (MEQ), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Occupational Fatigue Exhaustion/Recovery Scale (OFER). Repeated and one-way analyses of variance (ANOVAs), Pearson's chi-square tests, and correlation coefficients were used for statistical comparisons. Subjects slept an average of 06:28 h/night. Actigraphic sleep parameters, such as sleep duration, sleep efficiency, wake after sleep onset, and sleep latency, did not differ between chronotypes. Results also show that evening types (n = 17) presented lower subjective sleep quality than intermediate types (n = 58) and morning types (n = 13). Moreover, evening types reported higher levels of chronic work-related fatigue, exhibited less regular social rhythms, and were exposed to lower levels of light during their waking hours (between 2 and 11 h after wake time) as compared to intermediate types and morning types. In addition, exposure to light intensities between 100 and 500 lux was lower in evening types than in intermediate types and morning types. However, bright light exposure (≥1000 lux) did not differ between chronotypes. In conclusion, results suggest that student workers may constitute a high-risk population for sleep deprivation. Evening types seemed to cope less well with sleep deprivation, reporting poorer sleep quality and higher levels of work-related fatigue than intermediate types and morning types. The higher chronic work-related fatigue of evening types may be linked to their attenuated level of light exposure and weaker social zeitgebers. These results add credence to the hypothesis that eveningness entails a higher risk of health-impairing behaviors. (Author correspondence: luc.laberge@uqac.ca)

Melatonin Production and Light Exposure of Rotating Night Workers

Decreased melatonin production, due to acute suppression of pineal melatonin secretion by light exposure during night work, has been suggested to underlie higher cancer risks associated with prolonged experience of night work. However, the association between light exposure and melatonin production has never been measured in the field. In this study, 24-h melatonin production and ambulatory light exposure were assessed during both night-shift and day/evening-shift periods in 13 full-time rotating shiftworkers. Melatonin production was estimated with the excretion of urinary 6-sulfatoxymelatonin (aMT6s), and light exposure was measured with an ambulatory photometer. There was no difference in total 24-h aMT6s excretion between the two work periods. The night-shift period was characterized by a desynchrony between melatonin and sleep-wake rhythms, as shown by higher melatonin production during work and lower melatonin production during sleep when working night shifts than when working day/evening shifts. Light exposure during night work showed no correlation with aMT6s excreted during the night of work (p > .5), or with the difference in 24-h aMT6s excretion between the two work periods (p > .1). However, light exposure during night work was negatively correlated with total 24-h aMT6s excretion over the entire night-shift period (p < .01). In conclusion, there was no evidence of direct melatonin suppression during night work in this population. However, higher levels of light exposure during night work may have decreased total melatonin production, possibly by initiating re-entrainment and causing internal desynchrony. This interpretation is consistent with the proposition that circadian disruption, of which decreased melatonin production is only one of the adverse consequences, could be the mediator between night shiftwork and cancer risks. (Author correspondence: marie.dumont@umontreal.ca)

An Exploratory Study to Determine the Association Between Assessed Facial Skin Aging and Plasma Isoprostane Levels in Middle-Aged Japanese Women

One of the central mechanisms of aging is hypothesized to be oxidative stress. Quantification of oxidative stress in human organ systems has been difficult. One of the best methods is using plasma isoprostane levels, which have been shown to reflect oxidative stress in multiple nondermatologic organ systems. To determine whether severity of aging of human skin is associated with plasma isoprostane levels, specifically prostaglandin F2a (PGF2a) and 8-iso-PGF2a while controlling for covariates such as body mass index, ultraviolet light exposure, diet, medication, supplement use, and stress levels. Facial skin aging assessments performed by four blinded dermatologists were correlated with plasma isoprostane levels in 46 healthy, nonsmoking Japanese women aged 45 to 60. Individuals whose assessed skin age exceeded chronological age had mean plasma isoprostane levels of PGF2a and 8-iso-PGF2a that were higher than those whose skin age was assessed to be less than chronological age (p=.001 and .001, respectively). These results remained statistically significant when adjusted for confounding variables (8-iso-PGF2a, p=.02; PGF2a, p=.03). Plasma isoprostanes as markers of accelerated aging of the skin merit further study.

Light-dependent alteration of serotonin-1A receptor binding in cortical and subcortical limbic regions in the human brain

Objective. Climate, in particular sunshine, influences mood and energy levels, creating a positive upswing of mood on bright, sunny days and negative downswing in cold, dark winter seasons. Higher serotonin transporter availability in healthy human subjects in times of lesser light exposure and lower serotonin levels have been shown in winter. Methods. We examined the light-dependent variations in serotonin-1A receptor binding in limbic regions in 36 drug-naive healthy human subjects. Receptor binding was quantified using positron emission tomography and the radioligand [carbonyl-11C]WAY-100635. Binding potential values were related to the amount of individual exposure to sunlight (daily duration of sunshine) and global radiation (total light intensity). Results. We found a 20–30% lower serotonin-1A receptor binding in the group exposed to a lower amount of global light radiation. Partial correlation analysis revealed significant positive correlations between the regional postsynaptic serotonin-1A receptor binding and global radiation accumulated over a period of 5 days. Conclusions. Seasonal factors, such as daily amount of sunshine and global radiation, influence serotonin-1A receptor binding in limbic brain regions of healthy human subjects. Combined with recently demonstrated seasonal fluctuations in the serotonin transporter availability, our results underline the importance of seasonal factors in the regulation of the serotonergic transmission.

The Influence of Light at Night Exposure on Melatonin Levels among Canadian Rotating Shift Nurses

Shift work has been identified as a risk factor for several cancer sites in recent years, with melatonin as a potential intermediate on the proposed causal pathway. This study examined the influence of nighttime light exposure on melatonin levels among 123 rotating shift nurses. Nurses working a rotating shift schedule (two 12-hour days, two 12-hour nights, and five days off) were recruited and participated on a day and night shift in both the summer and winter seasons. Over each 48-hour study period, nurses wore a light data logger and provided two urine and four saliva samples. Saliva measurements showed that the pattern of melatonin production did not differ between day and night shifts. Mean light exposure was significantly higher (P < 0.0001) when nurses were working at night, although peak melatonin levels (P = 0.65) and the daily change in melatonin levels (P = 0.80) were similar across day/night shifts. Multivariate analysis did not show an association between light exposure and melatonin levels when data from both shifts was combined; however, when data from the night shift was considered alone, a statistically significant inverse relationship between light and change in melatonin was observed (P = 0.04). These results show that light exposure does not seem to be strongly related to reduced melatonin production among nurses on this rapidly rotating shift schedule. Future research considering more extreme shift patterns or brighter lighting conditions could further clarify the relationship between light exposure and melatonin production in observational settings.

Hydrogen Sulfide Protects the Retina from Light-induced Degeneration by the Modulation of Ca2+ Influx

Hydrogen sulfide (H(2)S) has recently been recognized as a signaling molecule as well as a cytoprotectant. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are well-known as H(2)S-producing enzymes. We recently demonstrated that 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT) produces H(2)S in the brain and in vascular endothelium. However, the cellular distribution and regulation of these enzymes are not well understood. Here we show that 3MST and CAT are localized to retinal neurons and that the production of H(2)S is regulated by Ca(2+); H(2)S, in turn, regulates Ca(2+) influx into photoreceptor cells by activating vacuolar type H(+)-ATPase (V-ATPase). We also show that H(2)S protects retinal neurons from light-induced degeneration. The excessive levels of light exposure deteriorated photoreceptor cells and increased the number of TUNEL- and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. Degeneration was greatly suppressed in the retina of mice administered with NaHS, a donor of H(2)S. The present study provides a new insight into the regulation of H(2)S production and the modulation of the retinal transmission by H(2)S. It also shows a cytoprotective effect of H(2)S on retinal neurons and provides a basis for the therapeutic target for retinal degeneration.