Photosensitive Retinal Ganglion Cells Research Articles

Non-image-forming photoreceptors improve visual orientation selectivity and image perception.

It has long been a decades-old dogma that image perception is mediated solely by rods and cones, while intrinsically photosensitive retinal ganglion cells (ipRGCs) are responsible only for non-image-forming vision, such as circadian photoentrainment and pupillary light reflexes. Surprisingly, we discovered that ipRGC activation enhances the orientation selectivity of layer 2/3 neurons in the primary visual cortex (V1) of mice by both increasing preferred-orientation responses and narrowing tuning bandwidth. Mechanistically, we found that the tuning properties of V1 excitatory and inhibitory neurons are differentially influenced by ipRGC activation, leading to a reshaping of the excitatory/inhibitory balance that enhances visual cortical orientation selectivity. Furthermore, light activation of ipRGCs improves behavioral orientation discrimination in mice. Importantly, we found that specific activation of ipRGCs in human participants through visual spectrum manipulation significantly enhances visual orientation discriminability. Our study reveals a visual channel originating from "non-image-forming photoreceptors" that facilitates visual orientation feature perception.

Developmental control of rod number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells.

Photoreception is essential for the development of the visual system, shaping vision's first synapse to cortical development. Here, we find that the lighting environment controls developmental rod apoptosis via Opn4-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). Using genetics, sensory environment manipulations, and computational approaches, we establish a pathway where light-dependent glutamate released from ipRGCs is detected via a transiently expressed glutamate receptor (Grik3) on rod precursors within the inner retina. Communication between these cells is mediated by hybrid neurites on ipRGCs that sense light before eye opening. These structures span the ipRGC-rod precursor distance over development and contain the machinery for photoreception (Opn4) and neurotransmitter release (Vglut2& Syp). Assessment of the human gestational retina identifies conserved hallmarks of an ipRGC-to-rod axis, including displaced rod precursors, transient GRIK3 expression, and ipRGCs with deep-projecting neurites. This analysis defines an adaptive retrograde pathway linking the sensory environment to rod precursors via ipRGCs prior to eye opening.

Light tunes a novel long-term threat avoidance behavior.

Animals must constantly scan their environment for imminent threats to their safety. However, they must also integrate their past experiences across long timescales to assess the potential recurrence of new threats. Though visual inputs are critical for the detection of environmental danger, whether and how visual information shapes an animal's assessment of whether a new threat is likely to reappear in a given context is unknown. Using a novel behavioral assessment of long-term threat avoidance behavior, we find that animals will avoid a familiar location where they previously experienced a single exposure to an innately threatening visual stimulus. This avoidance behavior is highly sensitive and lasts for multiple days. Intriguingly, we find that the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells tune this behavior via a perihabenular-nucleus accumbens circuit distinct from the canonical visual threat detection circuits. These findings define a specific retinal cell type driving a new long-term threat avoidance behavior driven by prior visual experience.

Environmental Light Controls the Daily Organization of Breathing by Activating Brn3b-expressing Intrinsically Photosensitive Retinal Ganglion Cells in Mice.

Rhythmic, daily fluctuations in minute ventilation are controlled by the endogenous circadian clock located in the suprachiasmatic nucleus (SCN). While light serves as a potent synchronizer for the SCN, it also influences physiology and behavior by activating Brn3b-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). It is currently unclear the extent to which the external light environment shapes daily ventilatory patterns independent of the SCN. To determine the relative influence of environmental light versus circadian timing on the organization of daily rhythms in minute ventilation, we used whole-body plethysmography to measure the breathing of mice housed on a non-entraining T28 cycle (14 h light:14 h dark). Using this protocol, we found that minute ventilation exhibits a ~28-h rhythm with a peak at dark onset that coincides with the light:dark cycle and the animals' locomotor activity. To determine if this 28-h rhythm in minute ventilation was mediated by Brn3b-expressing ipRGCs, we measured the breathing of Brn3bDTA mice housed under the T28 cycle. Brn3bDTA mice lack the Brn3b-expressing ipRGCs that project to many non-SCN brain regions. We found that despite rhythmic light cues occurring on a 28-h basis, Brn3bDTA mice exhibited 24-h rhythms in minute ventilation, locomotor activity, and core body temperature consistent with organization by the SCN. The 24-h minute ventilation rhythm of Brn3bDTA mice was found to be driven predominantly by tidal volume rather than respiratory rate. These data indicate that the external light:dark cycle can directly drive daily patterns in minute ventilation by way of Brn3b-expressing ipRGCs. In addition, these data strongly suggest that the activation of Brn3b-expressing ipRGCs principally organizes daily patterns in breathing and locomotor activity when light:dark cues are presented in opposition to endogenous clock timing.

In-silico predicted mouse melanopsins with blue spectral shifts deliver efficient subcellular signaling

Melanopsin is a photopigment belonging to the G Protein-Coupled Receptor (GPCR) family expressed in a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) and responsible for a variety of processes. The bistability and, thus, the possibility to function under low retinal availability would make melanopsin a powerful optogenetic tool. Here, we aim to utilize mouse melanopsin to trigger macrophage migration by its subcellular optical activation with localized blue light, while simultaneously imaging the migration with red light. To reduce melanopsin’s red light sensitivity, we employ a combination of in silico structure prediction and automated quantum mechanics/molecular mechanics modeling to predict minimally invasive mutations to shift its absorption spectrum towards the shorter wavelength region of the visible spectrum without compromising the signaling efficiency. The results demonstrate that it is possible to achieve melanopsin mutants that resist red light-induced activation but are activated by blue light and display properties indicating preserved bistability. Using the A333T mutant, we show that the blue light-induced subcellular melanopsin activation triggers localized PIP3 generation and macrophage migration, which we imaged using red light, demonstrating the optogenetic utility of minimally engineered melanopsins.

Effect of Diurnal Light Conditions on Electroretinogram Responses to Red and Blue Flickering Light.

Bright light impacts the human circadian system such that exposure to bright light at night can suppress melatonin secretion, and exposure to bright light in the morning prevents light-induced melatonin suppression at night. The preventive effect of morning light may attenuate the prior history of light sensitivity of intrinsically photosensitive retinal ganglion cells (ipRGCs) that regulate the circadian system. In this study, we evaluated electroretinogram (ERG) responses to red and blue flickering lights following dim and bright daylight conditions. Eleven healthy females underwent ERG measurements during exposure to 33Hz flickering red or blue light under dim and bright daytime conditions. We averaged ERG waves for 50 flickering light pulses of the trigger signal data. We obtained the amplitude of the signal-averaged ERG by calculating the difference between the waves' peaks and bottoms. Although there was no significant dim and bright light difference in the amplitude of ERG waves, the ERG amplitude to flickering blue light under the bright light condition was significantly lower than to flickering blue light under the dim light condition. In this study, blue light stimulated mainly ipRGCs and S-cones. Since S-cones may contribute minimally to the light-adapted 33Hz flicker ERG results, our findings suggest that bright light during the daytime attenuates the sensitivity of human ipRGCs.

Defining spatial nonuniformities of all ipRGC types using an improved Opn4cre recombinase mouse line

Intrinsically photosensitive retinal ganglion cells (ipRGCs) play a crucial role in several physiological light responses. In this study, we generate an improved Opn4cre knockin allele (Opn4cre(DSO)), which faithfully reproduces endogenous Opn4 expression and improves compatibility with widely used reporters. We evaluated the efficacy and sensitivity of Opn4cre(DSO) for labeling in retina and brain and provide an in-depth comparison with the extensively utilized Opn4cre(Saha) line. Through this characterization, Opn4cre(DSO) demonstrated higher specificity in labeling ipRGCs with minimal recombination escape. Leveraging a combination of electrophysiological, molecular, and morphological analyses, we confirmed its sensitivity in detecting all ipRGC types (M1-M6) and defined their unique topographical distribution across the retina. In the brain, the Opn4cre(DSO) line labels ipRGC projections with minimal labeling of cell bodies. Overall, the Opn4cre(DSO) mouse line represents an improved tool for studying ipRGC function and distribution, offering a means to selectively target these cells to study light-regulated behaviors and physiology.

Toward an Indoor Lighting Solution for Social Jet Lag.

There is growing interest in developing artificial lighting that stimulates intrinsically photosensitive retinal ganglion cells (ipRGCs) to entrain circadian rhythms to improve mood, sleep, and health. Efforts have focused on stimulating the intrinsic photopigment, melanopsin; however, specialized color vision circuits have been elucidated in the primate retina that transmit blue-yellow cone-opponent signals to ipRGCs. We designed a light that stimulates color-opponent inputs to ipRGCs by temporally alternating short- and long-wavelength components that strongly modulate short-wavelength sensitive (S) cones. Two-hour exposure to this S-cone modulating light produced an average circadian phase advance of 1 h and 20 min in 6 subjects (mean age = 30 years) compared to no phase advance for the subjects after exposure to a 500 lux white light equated for melanopsin effectiveness. These results are promising for developing artificial lighting that is highly effective in controlling circadian rhythms by invisibly modulating cone-opponent circuits.

Comparative analysis of circadian lighting models: melanopic illuminance vs. circadian stimulus.

The influence of light exposure on human circadian rhythms has been widely recognized. This effect is mediated by a phototransduction process projected by the intrinsically photosensitive retinal ganglion cells (ipRGCs). The process also involves signal inputs from visual photoreceptors. However, the relative contributions of each photoreceptor to this process remain unclear; accordingly, two different types of circadian lighting models have been proposed: (i) the melanopic illuminance model based solely on ipRGC activation, including melanopic equivalent daylight D65 illuminance (m-EDI) and equivalent melanopic illuminance (EML), and (ii) the circadian stimulus (CS) model, which considers the participation of both ipRGC and visual photoreceptors. However, the two models can yield conflicting predictions. In this study, we assessed and compared the accuracies of these circadian lighting models by fitting a substantial amount of experimental data extracted from multiple laboratory studies. Upon evaluating the results across all exposure durations, data-fitting accuracy of the intricate CS model did not surpass that of the much simpler melanopic illuminance model. Consequently, the latter appears to be the more suitable model for lighting applications. Moreover, a recurring limitation of prior research was revealed: the lighting spectra were not tailored to effectively reflect the fundamental distinctions between the two types of models. Therefore, drawing clear conclusions regarding the accuracies of the models is challenging. To address this problem, we introduced a method for designing contrast-spectra pairs. This method can provide lighting spectra to highlight the difference in circadian illuminance based on one model while keeping the circadian illuminance of others constant.

Hypersensitivity of Intrinsically Photosensitive Retinal Ganglion Cells in Migraine Induces Cortical Spreading Depression.

Migraine is a complex disorder characterized by episodes of moderate-to-severe, often unilateral headaches and generally accompanied by nausea, vomiting, and increased sensitivity to light (photophobia), sound (phonophobia), and smell (hyperosmia). Photophobia is considered the most bothersome symptom of migraine attacks. Although the underlying mechanism remains unclear, the intrinsically photosensitive retinal ganglion cells (ipRGCs) are considered to be involved in photophobia associated with migraine. In this study, we investigated the association between the sensitivity of ipRGCs and migraines and cortical spreading depression (CSD), which may trigger migraine attacks. The pupillary responses closely associated with the function of ipRGCs in patients with migraine who were irradiated with lights were evaluated. Blue (486 nm) light irradiation elicited a response from ipRGCs; however, red light (560 nm) had no such effect. Melanopsin, a photosensitive protein, phototransduces in ipRGCs following blue light stimulation. Hypersensitivity of ipRGCs was observed in patients with migraine. CSD was more easily induced with blue light than with incandescent light using a mouse CSD model. Moreover, CSD was suppressed, even in the presence of blue light, after injecting opsinamide, a melanopsin inhibitor. The hypersensitivity of ipRGCs in patients with migraine may induce CSD, resulting in migraine attacks.

Retinal inputs that drive optomotor responses of mice under mesopic conditions

Optomotor responses are a popular way to assess sub-cortical visual responses in mice. We studied photoreceptor inputs into optomotor circuits using genetically-modified mice lacking the exocytotic calcium sensors synaptotagmin 1 (Syt1) and 7 (Syt7) in rods or cones. We also tested mice that in which cone transducin, GNAT2, had been eliminated. We studied spatial frequency sensitivity under mesopic conditions by varying the spatial frequency of a grating rotating at 12 deg/s and contrast sensitivity by varying luminance contrast of 0.2c/deg gratings. We found that eliminating Syt1 from rods reduced responses to a low spatial frequency grating (0.05c/deg) consistent with low resolution in this pathway. Conversely, eliminating the ability of cones to respond to light (by eliminating GNAT2) or transmit light responses (by selectively eliminating Syt1) showed weaker responses to a high spatial frequency grating (3c/deg). Eliminating Syt7 from the entire optomotor pathway in a global knockout had no significant effect on optomotor responses. We isolated the secondary rod pathway involving transmission of rod responses to cones via gap junctions by simultaneously eliminating Syt1 from rods and GNAT2 from cones. We found that the secondary rod pathway is sufficient to drive robust optomotor responses under mesopic conditions. Finally, eliminating Syt1 from both rods and cones almost completely abolished optomotor responses, but we detected weak responses to large, bright rotating gratings that are likely driven by input from intrinsically photosensitive retinal ganglion cells.

Dopamine enhances GABAA receptor-mediated current amplitude in a subset of intrinsically photosensitive retinal ganglion cells.

Neuromodulation in the retina is crucial for effective processing of retinal signal at different levels of illuminance. Intrinsically photosensitive retinal ganglion cells (ipRGCs), the neurons that drive nonimage-forming visual functions, express a variety of neuromodulatory receptors that tune intrinsic excitability as well as synaptic inputs. Past research has examined actions of neuromodulators on light responsiveness of ipRGCs, but less is known about how neuromodulation affects synaptic currents in ipRGCs. To better understand how neuromodulators affect synaptic processing in ipRGC, we examine actions of opioid and dopamine agonists have on inhibitory synaptic currents in ipRGCs. Although µ-opioid receptor (MOR) activation had no effect on γ-aminobutyric acid (GABA) currents, dopamine [via the D1-type dopamine receptor (D1R)]) amplified GABAergic currents in a subset of ipRGCs. Furthermore, this D1R-mediated facilitation of the GABA conductance in ipRGCs was mediated by a cAMP/PKA-dependent mechanism. Taken together, these findings reinforce the idea that dopamine's modulatory role in retinal adaptation affects both nonimage-forming and image-forming visual functions.NEW & NOTEWORTHY Neuromodulators such as dopamine are important regulators of retinal function. Here, we demonstrate that dopamine increases inhibitory inputs to intrinsically photosensitive retinal ganglion cells (ipRGCs), in addition to its previously established effect on intrinsic light responsiveness. This indicates that dopamine, in addition to its ability to intrinsically modulate ipRGC activity, can also affect synaptic inputs to ipRGCs, thereby tuning retina circuits involved in nonimage-forming visual functions.

Pupillary Light Reflex Reveals Melanopsin System Alteration in the Background of Myopia-26, the Female Limited Form of Early-Onset High Myopia.

The purpose of this study was to evaluate pupillary light reflex (PLR) to chromatic flashes in patients with early-onset high-myopia (eoHM) without (myopic controls = M-CTRL) and with (female-limited myopia-26 = MYP-26) genetic mutations in the ARR3 gene encoding the cone arrestin. Participants were 26 female subjects divided into 3 groups: emmetropic controls (E-CTRL, N = 12, mean age = 28.6 ± 7.8years) and 2 myopic (M-CTRL, N = 7, mean age = 25.7 ± 11.5years and MYP-26, N = 7, mean age = 28.3 ± 15.4years) groups. In addition, one hemizygous carrier and one control male subject were examined. Direct PLRs were recorded after 10-minute dark adaptation. Stimuli were 1-second red (peak wavelength = 621nm) and blue (peak wavelength = 470nm) flashes at photopic luminance of 250 cd/m². A 2-minute interval between the flashes was introduced. Baseline pupil diameter (BPD), peak pupil constriction (PPC), and postillumination pupillary response (PIPR) were extracted from the PLR. Group comparisons were performed with ANOVAs. Dark-adapted BPD was comparable among the groups, whereas PPC to the red light was slightly reduced in patients with myopia (P = 0.02). PIPR at 6 seconds elicited by the blue flash was significantly weaker (P < 0.01) in female patients with MYP-26, whereas it was normal in the M-CTRL group and the asymptomatic male carrier. L/M-cone abnormalities due to ARR3 gene mutation is currently claimed to underlie the pathological eye growth in MYP-26. Our results suggest that malfunction of the melanopsin system of intrinsically photosensitive retinal ganglion cells (ipRGCs) is specific to patients with symptomatic MYP-26, and may therefore play an additional role in the pathological eye growth of MYP-26.

Prefrontal cortex neurons encode ambient light intensity differentially across regions and layers

While light can affect emotional and cognitive processes of the medial prefrontal cortex (mPFC), no light-encoding was hitherto identified in this region. Here, extracellular recordings in awake mice revealed that over half of studied mPFC neurons showed photosensitivity, that was diminished by inhibition of intrinsically photosensitive retinal ganglion cells (ipRGCs), or of the upstream thalamic perihabenular nucleus (PHb). In 15% of mPFC photosensitive neurons, firing rate changed monotonically along light-intensity steps and gradients. These light-intensity-encoding neurons comprised four types, two enhancing and two suppressing their firing rate with increased light intensity. Similar types were identified in the PHb, where they exhibited shorter latency and increased sensitivity. Light suppressed prelimbic activity but boosted infralimbic activity, mirroring the regions’ contrasting roles in fear-conditioning, drug-seeking, and anxiety. We posit that prefrontal photosensitivity represents a substrate of light-susceptible, mPFC-mediated functions, which could be ultimately studied as a therapeutical target in psychiatric and addiction disorders.

Circadian-independent light regulation of mammalian metabolism.

The daily light-dark cycle is a key zeitgeber (time cue) for entraining an organism's biological clock, whereby light sensing by retinal photoreceptors, particularly intrinsically photosensitive retinal ganglion cells, stimulates the suprachiasmatic nucleus of the hypothalamus, a central pacemaker that in turn orchestrates the rhythm of peripheral metabolic activities. Non-rhythmic effects of light on metabolism have also been long known, and their transduction mechanisms are only beginning to unfold. Here, we summarize emerging evidence that, in mammals, light exposure or deprivation profoundly affects glucose homeostasis, thermogenesis and other metabolic activities in a clock-independent manner. Such light regulation could involve melanopsin-based, intrinsically photosensitive retinal ganglion cell-initiated brain circuits via the suprachiasmatic nucleus of the hypothalamus and other nuclei, or direct stimulation of opsins expressed in the hypothalamus, adipose tissue, blood vessels and skin to regulate sympathetic tone, lipolysis, glucose uptake, mitochondrial activation, thermogenesis, food intake, blood pressure and melanogenesis. These photic signalling events may coordinate with circadian-based mechanisms to maintain metabolic homeostasis, with dysregulation of this system underlying metabolic diseases caused by aberrant light exposure, such as environmental night light and shift work.

Increase in choroidal thickness after blue light stimulation of the blind spot in young adults.

Blue light activates melanopsin, a photopigment that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs). The axons of ipRGCs converge on the optic disc, which corresponds to the physiological blind spot in the visual field. Thus, a blue light stimulus aligned with the blind spot captures the ipRGCs axons at the optic disc. This study examined the potential changes in choroidal thickness and axial length associated with blue light stimulation of melanopsin-expressing ipRGCs at the blind spot. It was hypothesized that blue light stimulation at the blind spot in adults increases choroidal thickness. The blind spots of both eyes of 10 emmetropes and 10 myopes, with a mean age of 28 ± 6 years (SD), were stimulated locally for 1-minute with blue flickering light with a 460nm peak wavelength. Measurements of choroidal thickness and axial length were collected from the left eye before stimulation and over a 60-minute poststimulation period. At a similar time of day, choroidal thickness and axial length were measured under sham control condition in all participants, while a subset of 3 emmetropes and 3 myopes were measured after 1-minute of red flickering light stimulation of the blind spot with a peak wavelength of 620nm. Linear mixed model analyses were performed to examine the light-induced changes in choroidal thickness and axial length over time and between refractive groups. Compared with sham control (2 ± 1μm, n = 20) and red light (-1 ± 2μm, n = 6) stimulation, subfoveal choroidal thickness increased within 60min after blue light stimulation of the blind spot (7 ± 1μm, n = 20; main effect of light, p < 0.001). Significant choroidal thickening after blue light stimulation occurred in emmetropes (10 ± 2μm, p < 0.001) but not in myopes (4 ± 2μm, p > 0.05). Choroidal thickening after blue light stimulation was greater in the fovea, diminishing in the parafoveal and perifoveal regions. There was no significant main effect of light, or light by refractive error interaction on the axial length after blind spot stimulation. These findings demonstrate that stimulating melanopsin-expressing axons of ipRGCs at the blind spot with blue light increases choroidal thickness in young adults. This has potential implications for regulating eye growth.

Cell-specific localization of β-synuclein in the mouse retina.

β-synuclein, a member of the synuclein family, is frequently co-expressed with α-synuclein in the neural system, where it serves to inhibit abnormal aggregation of α-synuclein in neurodegenerative diseases. Beyond its role in pathological conditions, β-synuclein plays various functions independently of α-synuclein. In our investigation, we discovered a broader expression of β-synuclein in the mouse retina compared to α-synuclein. This widespread pattern implies its potential significance in the retina. Through detailed examination via light- and electron-microscopic immunocytochemistry, we identified β-synuclein expression from the inner segment (IS) and outer segment (OS) of photoreceptor cells to the ganglion cell layer (GCL). Our findings unveiled unique features, including β-synuclein immunoreactive IS and OS of cones, higher expression in cone pedicles than in rod spherules, absence in horizontal cells, limited expression in cone bipolar dendrites and somas, higher expression in cone bipolar terminals, presence in most amacrine cells, and expression in almost majority of somas in GCL with an absence in intrinsically photosensitive retinal ganglion cell (ipRGCs) processes. Notably, all cholinergic amacrine cells express high β- but not α-synuclein, while dopaminergic amacrine cells express α-synuclein exclusively. These distinctive expression patterns offer valuable insights for further exploration into the functions of β-synuclein and its potential role in synuclein pathology within the retina.

Effect of hydrogen-rich saline on melanopsin after acute blue light-induced retinal damage in rats.

Excessive exposure to blue light can cause retinal damage. Hydrogen-rich saline (HRS), one of the hydrogen therapies, has been demonstrated to be effective in eye photodamage, but the effect on the expression of melanopsin in intrinsically photosensitive retinal ganglion cells (ipRGCs) is unknown. In this study, we used a rat model of light-induced retinal injury to observe the expression of melanopsin after HRS treatment and to determine the effect of HRS on retinal ganglion cell protection. Adult SD rats were exposed to blue light (48 h) and treated with HRS for 0, 3, 7, and 14 days. Real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) were performed to find the expression of genes and proteins, respectively. The function of retinal ipRGCs was measured by pattern-evoked electroretinography (pERG). The number and morphological changes of melanopsin-positive ganglion cells in the retina were observed by immunofluorescence (IF). Acute blue light exposure caused a decrease in ipRGC function, decreased expression of melanopsin protein and the melanopsin-positive RGCs, and diminished immunoreactivity in dendrites. However, over time, melanopsin showed a tendency to self-recovery, with an increase in melanopsin protein expression and the number of melanopsin-positive RGCs, with incomplete recovery of function within two weeks. HRS treatment accelerated the recovery process, with a significant increase in melanopsin expression and the number of melanopsin-positive RGCs, and an improvement in the pERG waveform within two weeks.

The structure-function relationship between multifocal pupil perimetry and retinal nerve fibre layer in glaucoma.

Multifocal pupillographic objective perimetry (mfPOP) is a novel method for assessing functional change in diseases like glaucoma. Previous research has suggested that, in contrast to the pretectally-mediated melanopsin response of intrinsically photosensitive retinal ganglion cells, mfPOP responses to transient onset stimuli involve the extrastriate cortex, and thus the main visual pathway. We therefore investigate the correlation between peripapillary retinal nerve fibre layer (pRNFL) thickness and glaucomatous visual field changes detected using mfPOP. Parallel analyses are undertaken using white on white standard automated perimetry (SAP) for comparison. Twenty-five glaucoma patients and 24 normal subjects were tested using SAP, 3 mfPOP variants, and optical coherence tomography (OCT). Arcuate clusters of the SAP and mfPOP deviations were weighted according to their contribution to published arcuate divisions of the retinal nerve fibre layer. Structure-function correlation coefficients (r) were computed between pRNFL clock-hour sector thickness measurements, and the local visual field sensitivities from both SAP and mfPOP. The strongest correlation was observed in the superior-superotemporal disc sector in patients with worst eye SAP MD < -12dB: r = 0.93 for the mfPOP LumBal test (p < 0.001). Correlations across all disc-sectors were strongest in these same patients in both SAP and mfPOP: SAP r = 0.54, mfPOP LumBal r = 0.55 (p < 0.001). In patients with SAP MD ≥ -6dB in both eyes, SAP correlations across all sectors were higher than mfPOP; mfPOP correlations however, were higher than SAP in more advanced disease, and in normal subjects. For both methods the largest correlations with pRNFL thickness corresponded to the inferior nasal field of more severely damaged eyes. Head-to-head comparison of mfPOP and SAP showed similar structure-function relationships. This agrees with our recent reports that mfPOP primarily stimulates the cortical drive to the pupils.

ICNIRP Statement on Short Wavelength Light Exposure from Indoor Artificial Sources and Human Health.

Concerns have been raised about the possibility of effects from exposure to short wavelength light (SWL), defined here as 380-550 nm, on human health. The spectral sensitivity of the human circadian timing system peaks at around 480 nm, much shorter than the peak sensitivity of daytime vision (i.e., 555 nm). Some experimental studies have demonstrated effects on the circadian timing system and on sleep from SWL exposure, especially when SWL exposure occurs in the evening or at night. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has identified a lack of consensus among public health officials regarding whether SWL from artificial sources disrupts circadian rhythm, and if so, whether SWL-disrupted circadian rhythm is associated with adverse health outcomes. Systematic reviews of studies designed to examine the effects of SWL on sleep and human health have shown conflicting results. There are many variables that can affect the outcome of these experimental studies. One of the main problems in earlier studies was the use of photometric quantities as a surrogate for SWL exposure. Additionally, the measurement of ambient light may not be an accurate measure of the amount of light impinging on the intrinsically photosensitive retinal ganglion cells, which are now known to play a major role in the human circadian timing system. Furthermore, epidemiological studies of long-term effects of chronic SWL exposure per se on human health are lacking. ICNIRP recommends that an analysis of data gaps be performed to delineate the types of studies needed, the parameters that should be addressed, and the methodology that should be applied in future studies so that a decision about the need for exposure guidelines can be made. In the meantime, ICNIRP supports some recommendations for how the quality of future studies might be improved.