Impact of Extended Exposure to LED Light on Retinal Metabolome, Cognitive Function, and Behaviour

doi:10.21203/rs.3.rs-4962896/v1

Download PDF

Article

Impact of Extended Exposure to LED Light on Retinal Metabolome, Cognitive Function, and Behaviour

https://doi.org/10.21203/rs.3.rs-4962896/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background: Exposure to short-wavelength LEDs, which are increasingly common in the digital era, particularly between 400 nm and 490 nm, can negatively impact the visual system and retinal metabolome. Thisstudy aimed to determine the effects of blue light exposure on retinal metabolomic changes and behaviour in rodents via gas chromatography/mass spectrometry (GC/MS).

Methodology: A total of 18 healthy adult male Wistar rats were randomly divided into six groups (n=6), three control (NC) groups (n=3), and three experimental (EXP) groups (n=3). The EXP animals were exposed to a 4-hour (4.00–8.00 pm) light cycle of blue LED light with uniform illumination (450–500 lux) throughout 14, 21, and 28 days. Postexposure, the rats were subjected to behavioural tests via the passive avoidance test (PAT). The animals were subjected to the elevated plus maze (EPM) test, and retinal tissue was removed to evaluate the metabolomic profile via GC-MS.

Results: The PAT showed a notable difference in latency (p=0.0317) between the groups. The EXP to blue light resulted in worsened motor memory and a longer latency to enter the dark compartment (DC). The EPM test did not reveal noteworthy variance in the time spent in the closed arm (TSICA) across sessions (p=0.1801). When retinal metabolites were compared between the groups, there was a notable difference (p < 0.0001), with the experimental groups having different levels of hydroxylamine.

Conclusion: Extended exposure to blue LED light can cause molecular changes in the retina that may lead to significant structural damage over time. This damage can result in alterations in learning and motor memory, which can persist for up to 28 days.

Biological sciences/Biochemistry

Earth and environmental sciences/Environmental sciences

Health sciences/Anatomy

Health sciences/Health care

Blue light-emitting diodes (LEDs)

light exposure

amino acids

light-induced damage

retinal metabolomics

The current 24/7 lifestyle and widespread use of electric illumination are accompanied by self-imposed changes in exposure patterns (1). Short-wavelength light is exposed daily due to the increasing use of digital device technology(2). This light is secure within a particular wavelength. Short-wavelength blue light has wavelengths between 400 and 490 nm, which could lead to detrimental effects (3). Various studies have been conducted on the impact of LED light and blue light exposure on the function and morphology of the retina (4). Intense light exposure to retinal tissue causes irremediable photochemical (5), photothermal and photomechanical damage (6), which impairs cellular function and stimulates apoptosis, along with the degradation of deoxyribonucleic acid (DNA) resulting from the generation of reactive oxygen species (ROS) (7). The pigmentary retina (RPE)(8), photoreceptor cells, and retinal ganglion cells (RGCs) are likely affected by high oxygen tension and blue light exposure, which may lead to a high degree of oxidative stress(9)(10). These mechanisms involve retinal ganglion cells, which are naturally sensitive (IpRGCs), and the chromophores of retinal cells activate these cells (7)

The intrinsically programmed indemnities constitute changes in the intraocular metabolomic environment of the retina (3). Photoreceptors, comprising more than 80% of retinal cells, have the highest metabolic demand in any tissue(11). Since light causes structural damage to the retina, it might lead to metabolic variations in neurosensory retinal layers. To compensate metabolomic requirements, the retina undergoes biochemical changes during preconditioning (12). Both pigmented and neural retinas are vulnerable to defects in retinal metabolism (13). This is because the biochemical alterations and retinal changes in the vitreous fluid are firmly related, as vitreous fluid causes the upregulation and downregulation of metabolites (7). Since cumulative exposure to blue light causes programmed damage (oxidative stress, cellular damage, and photochemical and photothermal damage), it might alter retinal metabolism (protein and amino acids) and diminish visual and nonvisual metabolism(10) (14).

Experimental studies suggest that oxygen diffused from the retina can be metabolised in the vitreous. Additionally, the lens and trabecular meshwork may be shielded from oxidative damage. The ability of molecules to absorb UV radiation and act as free radical inhibitors may help to shield and protect the lens and retina via the negative consequences of singlet oxygen synthesis driven by light (15). Animal light experiments have revealed that to maintain the structural and functional aspects of the retina, amino acids ((16), such as aspartate and glutamine, are necessary for both metabolism and neurotransmission (17). An alteration in the retina's metabolic state may impact retinal metabolomic distribution or release (16).

Although studies have explored the structural and functional aspects of the retina after light exposure, there is limited evidence of retinal metabolomic alterations after acute light exposure. Thus, we propose comprehending the connection between exposure to acute blue light at different intervals and retinal metabolomic remodelling.

Ethical statement

Approval for the study was obtained from the Institutional Research and the Animal Ethics Committee at Kasturba Medical College, MAHE (MCHP-mpl/IRC/PG/2023/034, IAEC/KMC/36/2023). All procedures involving the handling of animals were conducted in accordance with the ARRIVE guidelines.

Animals

In this research, we used eighteen adult male albino Wistar rats obtained from the Central Animal Research Facility (MAHE), weighing approximately 240 grams and eight weeks old. These rats were housed in sterile conditions, kept in polypropylene cages measuring 100 cm in length, 70 cm in width, and 50 cm in height, and were bedded with paddy husk. The rats had unlimited access to a standard pellet diet throughout the study.

The animals were divided into six groups, each comprising six. Specifically, three control groups (NC) with three rats each and three experimental groups (EXP) with three rats each. The experimental groups were subjected to blue LED light (3 W, InGan-series BL-chip) for four hours daily (from 4.00 pm to 8.00 pm) for 14, 21, and 28 days, respectively. In contrast, the rats in the control groups were maintained under standard laboratory conditions without exposure to the specified light cycle. The lighting setup for the experimental groups was arranged by mounting the light source 50 cm above the cages to maintain a luminosity level of 450–500 lux, replicating a standard laboratory environment, as detailed in Supplementary Figure 1.

Standardisation of light

Light standardisation was performed via a spectrometer (Asensetek Lighting Passport Pro, New Taipei City, Taiwan). By considering the geometry of the rat’s eye position horizontally and vertically (15), illumination at the surface and the bottom of the cage was measured (10). The instrument captures light waves of a particular wavelength, which are converted to the frequency spectrum and compared with the standard value (Supplementary Figure 1:), and retinal irradiance was calculated based on a previously published article(18).

Behavioural analysis

PAT

The rats were divided into control and light-exposed groups. They participated in PAT training, which was structured into three distinct components: the initial exploration phase, the conditioning trial, and a test for memory retention. In the exploration phase, rats were positioned at the centre of a larger enclosure (dimensions: 35 cm × 50 cm) adjacent to a more diminutive enclosure (dimensions: 15 cm × 15 cm). Five minutes were allotted for the rats to navigate the two enclosures, during which the duration spent in each enclosure and the instances of transition between them were meticulously documented. Subsequently, rats were returned to their respective enclosures.

The conditioning phase commenced on the subsequent day, where a fibreglass barrier sealed the opening (measuring 6 cm × 6 cm) that delineated the two enclosures. Upon entering the smaller enclosure, the animals were administered a series of electric shocks at five-second intervals. Each shock persisted for 2 seconds, with a frequency of 50 Hz and intensity set at 0.8 mA. Following this phase, subjects were relocated back to their original enclosures.

On the third day, the rats were subjected to an identical PAT protocol as that of the first day, with observations recorded regarding their time allocation in the larger versus smaller enclosures and their frequency of transitions between these spaces. Upon completing this task, the subjects were returned to their enclosures and provided with a three-day recuperation period to mitigate the effects of the shock treatment.

EPM

Following a period of three days dedicated to PAT, the rats were then evaluated using the EPM assessment. The EPM arms stood 40 cm above the floor, supported by synthetic stands. The enclosed arms had dimensions of 59 cm in length and 10 cm in width and were bordered by walls 50 cm tall, in contrast to the open arms, which lacked any barrier. Each rat was individually positioned at the juncture of these arms, away from the individual conducting the test. The exploration behaviours of the rats, specifically their mobility and their entries into both the open and enclosed arms, were documented over a five-minute duration using a video tracking system. The experimenter accurately recorded the frequency of entries and the duration spent by the rats in each arm type.

Retinal metabolomic analysis

Enucleation and storage

Post-behavioural tests, the rats were sacrificed with a fatal dosage of xylazine (10 ppm) and pentobarbital via intraperitoneal injection (i.p. 100 mg/kg) (Proxylaz). The rats were placed on a dry, level, smooth surface, and the surrounding areas and eyelids were cleaned with a cotton swab. Using sterilised forceps, the canthus was gently pressed to remove the eye from its socket and expose the optic nerve. The optic nerve was securely grasped while forceps were held behind the eye. With the forceps in hand, circular motions were made with the least resistance until the optic nerve was reduced to two. The detached eyeballs were extracted and stored in 4% paraformaldehyde to preserve the enucleated eyes. The retina was kept at a temperature of -80°C.

Homogenisation of retina

Mechanical homogenisation of the samples was performed by grinding the retinal tissues in liquid nitrogen with a precooled mortar and pestle (19). The mortar and pestle were precooled at -20°C for approximately one hour before the procedure. After each retinal sample was placed in the mortar, flash freezing was carried out by adding approximately 50 ml of liquid nitrogen to the retinal sample. The precooled pestle crushed and ground the frozen sample to a powder form (Supplementary Figure 2). The ground sample was then carefully removed via a spatula and collected in 1.5 ml microcentrifuge tubes (Thermo Fisher Scientific). The homogenised samples were stored at -80°C for further gas chromatography/mass spectrometry (GC/MS).

Sample preparation for GC‒MS

We used cryogenic processing using liquid nitrogen and added 1 ml of methanol to prepare retinal tissue to run GC-MS. To aid in quantification, we incorporated 40 µl of an internal standard, heptadecanoic acid, at a concentration of 0.5 mg/ml dissolved in ethyl acetate into each sample tube. The reaction mixture was then treated with 0.5 ml of 5% hydroxylamine hydrochloride (prepared by dissolving 5 g in 100 ml distilled water) and 400 µl of a 2.5 M sodium hydroxide solution to facilitate derivatisation, mixed thoroughly using a vortex mixer, and allowed to stabilise at ambient temperature for one hour. Subsequently, the mixture's pH was adjusted by adding 350 µl of 6 M hydrochloric acid and extracting the compounds of interest using 6 ml of ethyl acetate. Centrifugation of the mixture was performed at 3000 revolutions per minute for 5 minutes, after which 1 ml of the resultant supernatant was carefully transferred to a clean glass tube for further processing. The collected supernatant was then concentrated by evaporating to dryness at 40°C under a stream of nitrogen for 15 minutes. The residue obtained was resuspended in a mixture containing 20 µl of silyne and 200 µl of N-Methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA), sealed in aluminium foil to protect from light and heated at 80°C for 40 minutes in a dry bath to complete the derivatisation process. Finally, a 200 µl aliquot of the derivatised sample was placed into an insert vial for subsequent gas chromatography-mass spectrometry (GC-MS) analysis.

GC‒MS analysis and metabolite detection

Methanol extraction of the sample was performed using LC-MS grade solvent acquired from RCI Labscan and subjected to analysis utilising GC-MS (GC/MS—QP2020 NX, Shimadzu Corporation, Tokyo, Japan). The chromatographic separation of metabolites was achieved using an SH-I-5Sil MS capillary column measuring 30 m long with an internal diameter of 0.25 mm and a film thickness of 0.25 µm. An aliquot of 20 µl from each sample was introduced into the system by an autosampler at an injector temperature of 25°C. The separation process operated in a splitless mode, employing a mobile phase flow rate of 1.69 mL/min through the column. Helium gas was employed as the carrier medium at a 50 mL/min flow rate. The temperature protocol was initiated in the oven at 75°C, maintained for 4 minutes, followed by a rise to 280°C at a rate of 4°C per minute, before holding at this terminal temperature for 1.56 minutes. Operations in the mass spectrometer were conducted at an ion source temperature of 230°C and a transfer line temperature of 290°C, scanning masses ranging from 40 to 600 amu with a scan speed of 3333. A solvent delay was observed for 3 minutes, and overall, the MS operational duration was programmed for 56 minutes and 81 seconds. Identification of the metabolites utilised the NIST 2011 version spectral library.

Statistical analysis

The software Prism GraphPad version 6.0 was used to analyse the alterations in the rats' behaviour. One-way ANOVA and Tukey’s post hoc test were used to compare data across groups. Two-way ANOVA and the Bonferroni post hoc correction were used to analyse the GC/MS data.

PAT

We aimed to determine the effects of acute exposure to blue LED light on the behaviour of rats. The latency to enter the dark compartment (DC) on the first and third days was considered (Figure 1a&1b). The groups' mean latency was compared via one-way ANOVA, and a significant difference was detected (F=_3.613p=0.0317) between EXP 21-EXP 28 on the first day and EXP 21-NC 28 on the third day (F=_3.149p=0.0480). Following post hoc analysis, a noteworthy distinction was found (p<0.05) between EXP 21 and EXP 28 on the first day, whereas no difference was detected in EXP 14 on the same day (p>0.05). During the exploration phase, none of the groups significantly differed in the time taken to return to the light compartment (TTRBLC) from the dark compartment (DC) (F=_2.940 p=0.0584) (Figure 1c). There was a significant difference (F=_5.949 p=0.0054) on the third day between EXP 14--NC 21 (P<0.05), EXP 14--NC 28 (P<0.05), and EXP 14--EXP 21 (p<0.05) (Figure 1d). The time spent in the dark compartment (TSIDC) on the third-day post-shock treatment was not significantly different among the groups (F=_2.429_, p=0.0965) (Figure 1f). However, a considerable difference (F=_5.923 p=0.0055) occurred in the TSIDC during the exploration phase (Figure 1e). Post hoc analysis revealed substantial differences between NC 14-NC 21 (p<0.01), NC 14-NC 28 (p<0.05), and NC 14-EXP 28 (p<0.05). Finally, neither the retention phase (F=_0.5000 p=0.7708) (Figure 1h) nor the exploration phase (F=_1.044 p=0.4360) (Figure 1g) presented a statistically significant number of crossings (NOC) between the light compartment (LC) and DC.

EPM

Our study analyzed the behavioural responses of normal control rats and those exposed to blue LED light, explicitly focusing on their activity within an Elevated Plus Maze (EPM) apparatus after undergoing the Passive Avoidance Test (PAT) for three days. The duration required for the subjects to venture into and exit the open arms of the EPM was meticulously recorded (as illustrated in Figure 2a and 2b, respectively). Our findings indicated a statistically significant difference in the time it took for the subjects to enter the open arms across both groups (F=_3.550, p=0.0335), with further analysis identifying a notable difference between the NC14 and NC21 subgroups (p<0.05). Conversely, the time to return from the open arms to the centre did not display a significant disparity (F=_2.731, p=0.0714), similar to the entries into and exits from the closed arms, which were also not significantly different (F=_1.291, p=0.3304 for entry and F=_1.187, p=0.3713 for exit, as shown in Figures 2c&2d, respectively).

Moreover, no significant variation was observed in the average duration spent within the closed arms across sessions (F=_1.836, p=0.1801, see Figure 2f). However, a significant difference in the time spent in the open arms was detected (F=_3.886, p=0.0251), especially after conducting post-hoc analysis between the NC28 and groups, indicating a significant disparity (p<0.05) as depicted in Figure 2e. Lastly, the aggregate mean time spent at the maze's centre did not significantly vary among the groups, as determined by a one-way ANOVA (F=_0.8969, p=0.5136; Figure 2g).

Results of GC-MS

Our study examined eighteen retinal specimens assigned to control (NC) and experimental (EXP) cohorts, utilizing the NIST Version 2011 for our analysis. The investigation identified roughly 150 metabolites within each cohort. Notably, nine similar compounds were detected across the two groups (NC 14, EXP 14, NC 21, EXP 21, NC 28, and EXP 28). Through employing a two-way ANOVA, we scrutinised both the area (illustrated in Figure 3a) and the peak heights (depicted in Figure 3b) of the metabolites for each group, uncovering raw factor values of 62.20 and 65.32, respectively, with associated p<0.0001.

Further scrutiny into the area on the hydroxylamine (NH2OH) metabolite showcased notable variance between the groups NC 14 and NC 21 (p<0.01), between EXP 14 and NC 21 (p<0.001), between EXP 14 and EXP 21 (p<0.01), between EXP 14 and NC 28 (p<0.01), and finally between EXP 14 and EXP 28 (p=0.001). Comparable significant disparities were noted in peak heights for identical group comparisons, with p-values of less than 0.01 in most instances, thereby underscoring the impact of blue light on retinal metabolite profiles, particularly concerning hydroxylamine metabolites. These alterations have potent implications for retinal health. Further, to pinpoint the metabolic pathways influenced by light exposure in animals, we used MetaboAnalyst 6.0 for our metabolomic data examination. This analysis highlighted a prominent alteration in the linoleic acid metabolic process and the biosynthesis of unsaturated fatty acids within the light-exposed cohorts, marked by p-values of less than 0.05. As a result of light exposure, such perturbations in metabolic processes suggest a detrimental effect on the photochemical metabolism in animals, particularly the linoleic acid pathway, as visualised in Figure 4.

The study revealed that exposure to blue LEDs for 28 (4:00 hours) days resulted in impaired cognitive functions (learning and memory) and elevated anxiety with altered hydroxylamine levels. These effects may be caused by molecular level changes (20), light-induced stress, circadian rhythm alterations, or hippocampal modifications in the CA1 and CA3 regions (21). Furthermore, this exposure may have affected the prefrontal cortex and ipRGCs of the retina (22). The results of this research complement the observations of 28 days of cumulative blue LED light exposure for a 12:12 period with uniform illumination of 450–500 lux, which resulted in impaired cognitive functions (learning and memory), elevated anxiety levels and decreased melatonin levels (23), affecting image-forming and non-image-forming functions (21). Short-term acute blue LED light exposure for four hours daily is consistent with previous research. Hydroxylamine substantially changed on the 14th, 21st, and 28th days of exposure to the nine significant metabolites. Altered hydroxylamine could be due to photochemical damage to photoreceptor and RPE levels (24). This hydroxylamine directly impacts photoreceptors, inhibiting the light-dependent phosphorylation of rhodopsin by directly inhibiting the production of rhodopsin and ATP (24). This inhibition can cause photoreceptor degeneration, resulting in continued apoptotic activity(25), oxidative stress, and structural alterations of the retina and hippocampus along with changes in the IpRGC, which project into the suprachiasmatic nucleus (SCN)(26). These changes may negatively impact or harm the photochemistry of vision and cause changes in the complexity of the basal dendrites of hippocampal neurons in the CA1 and CA3 regions and functional deficits in spatial learning and memory(21).

The subsequent disruption of natural light-dark lighting for one-week results in changes in behaviour and physiology suggestive of stress (27),(28),(29) in male mice, resulting in elevated levels of plasma corticosterone (30), affecting both glucocorticoid and mineralocorticoid receptors throughout the brain, including the hippocampus (31). Neurotransmitter levels decline in animals exposed to light and dark, supporting the theory that prolonged exposure reduces dopamine and metabolites in the striatum of rodents (32). A reward-motivated neurotransmitter, dopamine, is directly related to stress and sleep. It is downregulated during stressful situations involving light and dark exposure (33). Changes in hydroxylamine levels can considerably impact neural systems beyond visual systems. When exposed to light, rods lose their structural integrity, which disrupts the connection between metarhodopsin II and proteins. As a result, hydroxylamine binds to the retinal binding site of metarhodopsin, significantly affecting the neural and visual systems (24). Recent studies have demonstrated that the addition of hydroxylamine partially hinders phosphorylation in the retina (34) (35). Additionally, the decay of metarhodopsin II, which follows bleaching, was significantly accelerated by two mM hydroxylamines. However, the overall time course of rod dark adaptation has remained unchanged (34). On the other hand, experiments conducted on isolated, bleached retinas of rats revealed that the dark adaptation kinetics of the rod were unaffected by one mM hydroxylamine (35). Therefore, more work is needed to quantify hydroxylamine metabolites to explore their photochemistry further.

Evidence suggests that acute exposure to blue LED light can cause neuronal changes and stress in animals, impacting their memory and potentially affecting the neuronal system when animals are exposed to LEDs for extended periods(36). However, minimal alterations were noted on the 14th and 21st days of exposure, potentially due to the self-protective mechanism through which the animals developed. Further studies are necessary to address this issue. Our research investigated the effects of acute light exposure to blue LEDs on rats. This study aimed to observe the resulting molecular changes in the retina and any related behavioural changes in animals exposed to light for a shorter duration. This study serves as base-level research to be built upon in future studies.

Rat eyes are 25 times smaller and more transparent than human eyes, which means that there is a more significant potential for harm from light absorption. To add more value to this study, we considered functional modifications such as electroretinography (ERG), even though the results may not directly apply to humans. This technique possibly enabled us to gauge the retina’s electrical activity in response to light stimulation, which offered more information about how exposure to blue LEDs affects the retina. Overall, this research provides valuable insights into the consequences of blue LED exposure on retina and rat behaviour. According to previous studies, the outer nuclear layer of the retina may be thin due to short-term exposure to blue LED light. However, this effect was reversible after the healing period, and the thickness returned to normal. This research investigated the potential harm caused by light exposure to the metabolites present in the retina. The findings of this study indicate a noticeable change in the levels of a chemical messenger within the retina, which can significantly impact learning and motor behaviour. Moreover, acute light exposure can alter these behaviours. Therefore, exercising caution in acute light exposure is essential, as acute light exposure can harm the retina and overall health.

The targeted analysis of metabolomics and related biomarkers of the retinal pigment epithelium (RPE) has the potential to provide valuable insights into the molecular changes occurring within this tissue. By mapping these changes, we can complement and enhance the results we have already obtained. This approach could improve our understanding of RPE function and pathology and ultimately lead to the development of better diagnostic and therapeutic strategies.

Extended exposure to blue LED light can cause molecular changes in the retina that may lead to significant structural damage over time. This damage can result in alterations in learning and motor memory, which can persist for up to 28 days. The blue spectrum of LED lights has been found to potentially cause molecular, structural and functional damage, raising concerns about the potential adverse effects of this type of lighting. Therefore, it is crucial to be cautious with prolonged exposure to blue LED lights to avoid negative impacts on health and well-being. Preventative measures such as limiting the exposure time, using protective filters, and adjusting the light intensity can help mitigate the potential risks of blue LED lights.

Conflict of interest:

Nil

Author Contribution

Conceptualisation, N.T., A.Y., R.S., and DK. .; methodology, N.T., A.Y., R.S., P.M., M.B., M.S., A.A., and DK. .; software., A.Y., R.S., P.M., M.B., M.S., A.A., and DK. .validation., N.T., R.S., P.M., M.B., M.S., and A.A.; investigation, N.T., A.Y., R.S., and DK resources, N.T., A.Y., R.S., P.M., M.B., M.S., A.A., and DK. data curation, N.T., P.M., M.B., M.S., and A.A.; writing-original draft preparation, N.T., A.Y., R.S., and DK. writing-review and editing, .T., R.S., P.M., M.B., M.S., and A.A. visualisation, N.T., R.S., P.M., M.B., M.S., and A.A. supervision, N.T., R.S., P.M., M.B., M.S., and A.A. All authors have read and agreed to the published version of the manuscript.

Acknowledgement

We would like to acknowledge the institutional review committee (MCHP) for their valuable input during the study protocol and the MAHE Manipal for supporting student SEED Money.

Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request

Cheung IN, Zee PC, Shalman D, Malkani RG, Kang J, Reid KJ. Morning and evening blue-enriched light exposure alters metabolic function in normal-weight adults. PloS one. 2016 May 18;11(5): e0155601.
Lin JB, Gerratt BW, Bassi CJ, Apte RS. Short-wavelength light-blocking eyeglasses attenuate symptoms of eye fatigue. Investigative ophthalmology & visual science. 2017 Jan 1;58(1):442-7.
Li H, Zhang M, Wang D, Dong G, Chen Z, Li S, Sun X, Zeng M, Liao H, Chen H, Xiao S. Blue light from cell phones can cause chronic retinal light injury: the evidence from a clinical observational study and an SD rat model. BioMed Research International. 2021 May 16; 2021:1-3.
Shang YM, Wang GS, Sliney D, Yang CH, Lee LL. White light–emitting diodes (LEDs) at domestic lighting levels and retinal injury in a rat model. Environmental health perspectives. 2014 Mar;122(3):269-76.
Kim GH, Kim HI, Paik SS, Jung SW, Kang S, Kim IB. Functional and morphological evaluation of blue light-emitting diode-induced retinal degeneration in mice. Graefe's Archive for Clinical and Experimental Ophthalmology. 2016 Apr; 254:705-16.
Zhao ZC, Zhou Y, Tan G, Li J. Research progress about the effect and prevention of blue light on eyes. International journal of ophthalmology. 2018;11(12):1999.
Wu J, Seregard S, Algvere PV. Photochemical damage of the retina. Survey of ophthalmology. 2006 Sep 1;51(5):461-81.
Nagarajan TN, Joshi MB, Valiathan M, Rao SB, Bhat S, Surendran S. The effect of different bands of LED exposure on vitreous metabolites and retinal architecture.
Sahin K, Gencoglu H, Akdemir F, Orhan C, Tuzcu M, Sahin N, Yilmaz I, Juturu V. Lutein and zeaxanthin isomers may attenuate photooxidative retinal damage via modulation of G protein-coupled receptors and growth factors in rats. Biochemical and biophysical research communications. 2019 Aug 13;516(1):163-70.
Osborne NN, Núñez-Álvarez C, del Olmo-Aguado S. The effect of visual blue light on mitochondrial function associated with retinal ganglion cells. Experimental eye research. 2014 Nov 1; 128:8-14.
Akansha EO, Bui BV, Ganeshrao SB, Bakthavatchalam P, Gopalakrishnan S, Mattam S, Poojary RR, Jathanna JS, Jose J, Theruveethi NN. Blue-Light-Blocking Lenses Ameliorate Structural Alterations in the Rodent Hippocampus. International Journal of Environmental Research and Public Health. 2022 Oct 9;19(19):12922.
Murenu E, Kostidis S, Lahiri S, Geserich AS, Imhof A, Giera M, Michalakis S. Metabolic analysis of vitreous/lens and retina in wild type and retinal degeneration mice. International Journal of Molecular Sciences. 2021 Feb 26;22(5):2345.
de La Barca JM, Huang NT, Jiao H, Tessier L, Gadras C, Simard G, Natoli R, Tcherkez G, Reynier P, Valter K. Retinal metabolic events in preconditioning light stress as revealed by wide-spectrum targeted metabolomics. Metabolomics. 2017 Mar; 13:1-3.
Xu R, Ritz BK, Wang Y, Huang J, Zhao C, Gong K, Liu X, Du J. The retina and retinal pigment epithelium differ in nitrogen metabolism and are metabolically connected. Journal of Biological Chemistry. 2020 Feb 21;295(8):2324-35.
Provencio. I, Cooper HM, Foster RG, Hannibal; J. Phototransduction by Retinal Ganglion Cells That Set the Circadian Clock [Internet]. Vol. 395, Neurosci. Biobehav. Rev. 1998. Available from: http://science.sciencemag.org/
Nagarajan TN, Joshi MB, Ganeshrao SB, Valiathan M, Surendran S. Blue LED light exposure induces metabolic rewiring in vitreous tissues in rat models. Journal of King Saud University-Science. 2022 Jun 1;34(4):101986.
Kalloniatis M, Tomisich G. Amino acid neurochemistry of the vertebrate retina. Progress in retinal and eye research. 1999 Nov 1;18(6):811-66.
Kalloniatis M, Loh CS, Acosta ML, Tomisich G, Zhu Y, Nivison‐Smith L, Fletcher EL, Chua J, Sun D, Arunthavasothy N. Retinal amino acid neurochemistry in health and disease. Clinical and Experimental Optometry. 2013 May 1;96(3):310-32.
Sliney DH. Quantifying retinal irradiance levels in light damage experiments. Current Eye Research. 1984 Jan 1;3(1):175-80.
Joylin S, Mutalik S, Kalaivani M, Shenoy RP, Ghosh M, Kumar EO, Theruveethi N. Influence of different LED wavelengths on retinal melatonin levels A rodent study. Science of The Total Environment. 2023 Dec 15; 904:166665.
Abı́lio VC, Freitas FM, Dolnikoff MS, Castrucci AM, Frussa-Filho R. Effects of continuous exposure to light on behavioural dopaminergic supersensitivity. Biological Psychiatry. 1999 Jun 15;45(12):1622-9.
Ewbank R. The Assessment of Stress in Laboratory Animals Caroline E Manser (1992). RSPCA: Horsham. 208 pp. Paperback. Obtainable from the publishers, The Royal Society for the Prevention of Cruelty to Animals, Causeway, Horsham, West Sussex RH12 1HG, UK. Price£ 7 including postage. Animal Welfare. 1993 Nov;2(4):368-9.
Van Loo PL, Van der Meer E, Kruitwagen CL, Koolhaas JM, Van Zutphen LF, Baumans V. Long-term effects of husbandry procedures on stress-related parameters in male mice of two strains. Laboratory animals. 2004 Apr 1;38(2):169-77.
Van der Meer E, Van Loo PL, Baumans V. Short-term effects of a disturbed light-dark cycle and environmental enrichment on aggression and stress-related parameters in male mice. Laboratory Animals. 2004 Oct 1;38(4):376-83.
Reiter RJ, Tan DX, Korkmaz A, Ma S. Obesity and metabolic syndrome: association with chronodisruption, sleep deprivation, and melatonin suppression. Annals of medicine. 2012 Sep 1;44(6):564-77.
Romeo S, Viaggi C, Di Camillo D, Willis AW, Lozzi L, Rocchi C, Capannolo M, Aloisi G, Vaglini F, Maccarone R, Caleo M. Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology. Scientific reports. 2013 Mar 6;3(1):1395.
Al-Asmari AR, Riyasdeen A, Al-Shahrani HM, Idris MM. Role of Neurotransmitter and Behavioral Changes in Mice Due to Light-Dark Stress. Neurochem Neuropharm Open Access. 2015;1(103):2.
Theruveethi N, Bui BV, Joshi MB, Valiathan M, Ganeshrao SB, Gopalakrishnan S, Kabekkodu SP, Bhat SS, Surendran S. Blue light-induced retinal neuronal injury and amelioration by commercially available blue light-blocking lenses. Life. 2022 Feb 7;12(2):243.
Fonken, L. K., & Nelson, R. J. (2014). The effects of light at night on circadian clocks and metabolism. Endocrine Reviews, 35(4), 648–670. https://doi.org/10.1210/er.2013-1051
Pepperberg, D. R., & Okajima, T. I. (1992). Hydroxylamine-dependent inhibition of rhodopsin phosphorylation in the isolated retina. Experimental eye research, 54(3), 369–376. https://doi.org/10.1016/0014-4835(92)90049-x
Lee, H. H., Tu, Y. C., & Yeh, S. L. (2021). In search of blue-light effects on cognitive control. Scientific reports, 11(1), 15505. https://doi.org/10.1038/s41598-021-94989-6
Brin, K. P., & Ripps, H. (1977). Rhodopsin photoproducts and rod sensitivity in the skate retina. The Journal of General Physiology, 69(1), 97–120. https://doi.org/10.1085/jgp.69.1.97
Kolesnikov, A. V., Fan, J., Crouch, R. K., & Kefalov, V. J. (2010). Age-related deterioration of rod vision in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30(33), 11222–11231. https://doi.org/10.1523/JNEUROSCI.4239-09.2010
Naz, S., Moreira dos Santos, D. C., García, A., & Barbas, C. (2014). Analytical protocols based on LC‒MS, GC‒MS and CE-MS for nontargeted metabolomics of biological tissues. Bioanalysis, 6(12), 1657–1677. https://doi.org/10.4155/bio.14.119
Schaefer, T. L., Grace, C. E., Gudelsky, G. A., Vorhees, C. V., & Williams, M. T. (2010). Effects on plasma corticosterone levels and brain serotonin from interference with methamphetamine-induced corticosterone release in neonatal rats. Stress, 13(6), 469–480. https://doi.org/10.3109/10253891003786407
Li, Z., Lee, C. S., Chen, S., He, B., Chen, X., Peng, H. Y., Lin, T. B., Hsieh, M. C., Lai, C. Y., & Chou, D. (2023). Blue light at night produces stress-evoked heightened aggression by enhancing brain-derived neurotrophic factor in the basolateral amygdala. Neurobiology of stress, 28, 100600. https://doi.org/10.1016/j.ynstr.2023.100600
Sliney D. H. (1984). Quantifying retinal irradiance levels in light damage experiments. Current eye research, 3(1), 175–179. https://doi.org/10.3109/02713688408997199

No competing interests reported.

Supplimentary1.tif
Supplementary Figure 1: NC (A) and EXP (B) albino Wistar rats are being handled while they are in their cages. C) Blue LED spectral transmission, with the Y axis representing the relative intensity of light transmission and the X axis representing the wavelength in nm. D) Passive avoidance apparatus with dark and light compartments. E) Elevated plus maze apparatus.

Download PDF

Reviews received at journal
24 Oct, 2024
Reviews received at journal
23 Oct, 2024
Reviewers agreed at journal
14 Oct, 2024
Reviewers agreed at journal
14 Oct, 2024
Reviewers agreed at journal
12 Oct, 2024
Reviewers invited by journal
12 Oct, 2024
Editor assigned by journal
06 Oct, 2024
Editor invited by journal
05 Sep, 2024
Submission checks completed at journal
05 Sep, 2024
First submitted to journal
23 Aug, 2024

You are reading this latest preprint version

Impact of Extended Exposure to LED Light on Retinal Metabolome, Cognitive Function, and Behaviour

Status:

Version 1

Abstract

Figures

Introduction

Methodology

Results of behavioural analysis

Discussion

Conclusion

Declarations

Conflict of interest:

Author Contribution

Acknowledgement

Data Availability

References

Additional Declarations

Supplementary Files

Status:

Version 1