Effect of Age and Refractive Error on the Melanopsin Mediated Post-Illumination Pupil Response (PIPR).
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ABSTRACT:
SUBMITTER: Adhikari P
PROVIDER: S-EPMC4664956 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:PurposeHuman and animal studies suggest that light-mediated dopamine release may underlie the protective effect of time outdoors on myopia development. Melanopsin-containing retinal ganglion cells may be involved in this process by integrating ambient light exposure and regulating retinal dopamine levels. The study evaluates this potential involvement by examining whether melanopsin-driven pupillary responses are associated with adult refractive error.MethodsSubjects were 45 young adults (73% female, 24.1 ± 1.8 years) with refractive errors ranging from -6.33 D to +1.70 D. The RAPDx (Konan Medical) pupillometer measured normalized pupillary responses to three forms of square-wave light pulses alternating with darkness at 0.1 Hz: alternating long wavelength (red, peak at 608 nm) and short wavelength (blue, peak at 448 nm), followed by red only and then blue only.ResultsNon-myopic subjects displayed greater pupillary constriction in the blue-only condition and slower redilation following blue light offset than subjects with myopia (P = 0.011). Pupillary responses were not significantly different between myopic and non-myopic subjects in the red-only condition (P = 0.15). More hyperopic/less myopic refractive error as a continuous variable was linearly related to larger increases in pupillary constriction in response to blue-only stimuli (r = 0.48, P = 0.001).ConclusionsRepeated light exposures to blue test stimuli resulted in an adaptation in the pupillary response (more constriction and slower redilation), presumably due to increased melanopsin-mediated input in more hyperopic/less myopic adults. This adaptive property supports a possible role for these ganglion cells in the protective effects of time outdoors on myopia development.
| S-EPMC7594593 | biostudies-literature
Project description:We collected and analyzed pupil diameter data from of 7 visually normal participants to compare the maximum pupil constriction (MPC) induced by "Red Only" vs. "Blue+Red" visual stimulation conditions. The "Red Only" condition consisted of red light (640±10 nm) stimuli of variable intensity and duration presented to dark-adapted eyes with pupils at resting state. This condition stimulates the cone-driven activity of the intrinsically photosensitive retinal ganglion cells (ipRGC). The "Blue+Red" condition consisted of the same red light stimulus presented during ongoing blue (470±17 nm) light-induced post-illumination pupil response (PIPR), representing the cone-driven ipRGC activity superimposed on the melanopsin-driven intrinsic activity of the ipRGCs ("The Absence of Attenuating Effect of Red light Exposure on Pre-existing Melanopsin-Driven Post-illumination Pupil Response" Lei et al. (2016) [1]). MPC induced by the "Red Only" condition was compared with the MPC induced by the "Blue+Red" condition by multiple paired sample t-tests with Bonferroni correction.
| S-EPMC5036441 | biostudies-literature
Project description:PURPOSE:The intrinsically photosensitive retinal ganglion cells (ipRGCs) signal environmental light, control pupil size and entrain circadian rhythm. There is speculation that ipRGCs may be involved in the protective effects of light exposure in myopia. Here, the ipRGC-driven pupil response was evaluated in children and examined with light exposure and refractive error. METHODS:Children ages 5-15 years participated. Subjects wore an actigraph device prior to the lab visit for objective measures of light exposure and sleep. For pupillometry, the left eye was dilated and presented with stimuli, and the consensual pupil response was measured in the right eye. Pupil measurements were preceded by 5 min dark adaptation. In Experiment 1 (n = 14), 1 s long wavelength light ('red,' 651 nm, 167 cd m-2 ) and 10 increasing intensities of 1 s short wavelength light ('blue,' 456 nm, 0.167-167 cd m-2 ) were presented with a 60 s interstimulus interval. A piecewise two-segment regression was fit to the stimulus response function to determine the functional melanopsin threshold. Pupil responses were analysed with light exposure over the previous 24 h. For Experiment 2 (n = 42), three 1 s red and three 1 s blue alternating stimuli were presented with a 60 s interstimulus interval. Following an additional 5-min dark adaption, the experiment was repeated. Pupil metrics included peak constriction, the 6 s and 30 s post-illumination response (PIPR), early and late area under the curve (AUC). Following pupil measurements, cycloplegic refractive error and axial length were measured. RESULTS:For Experiment 1, PIPR metrics demonstrated a graded response to increasing intensity blue stimuli, with a mean functional melanopsin threshold of 6.2 ± 4.5 cd m-2 (range: 0.84-16.7 cd m-2 ). The 6 s PIPR and early AUC were associated with 24-h light exposure for high intensity stimuli (33.3 and 83.3 cd m-2 , p < 0.005 for both). For Experiment 2, there were no associations between pupil metrics and refractive error. The 6 s PIPR and early AUC to blue stimuli were significantly increased for Trial 2 compared to Trial 1. CONCLUSIONS:The ipRGC-driven pupil responses in children were robust and similar to responses previously measured in an adult population. The 6 s PIPR and early AUC to high intensity blue stimuli were associated with previous light exposure. There were no associations between the ipRGC-driven pupil response and refractive status in this cohort.
| S-EPMC6202139 | biostudies-literature
Project description:Individuals with seasonal affective disorder (SAD) may have a decreased retinal sensitivity in the non-image forming light-input pathway. We examined the post illumination pupil response (PIPR) among individuals with SAD and healthy controls to identify possible differences in the melanopsin signaling pathway. We also investigated whether melanopsin gene (OPN4) variations would predict variability in the PIPR. Fifteen SAD and 15 control participants (80% women, mean age 36.7 years, S.D.=14.5) were assessed in the fall/winter. Participants were diagnosed based on DSM-IV-TR criteria. Infrared pupillometry was used to measure pupil diameter prior to, during, and after red and blue stimuli. In response to blue light, the SAD group had a reduced PIPR and a lower PIPR percent change relative to controls. The PIPR after the blue stimulus also varied on the basis of OPN4 I394T genotype, but not OPN4 P10L genotype. These findings may indicate that individuals with SAD have a less sensitive light input pathway as measured by the PIPR, leading to differences in neurobiological and behavioral responses such as alertness, circadian photoentrainment, and melatonin release. In addition, this sensitivity may vary based on sequence variations in OPN4, although a larger sample and replication is needed.
| S-EPMC3795919 | biostudies-literature
Project description:We conducted a cross-sectional study on 403 participants in the 10-year follow-up examination of the Beaver Dam Offspring Study. The participants included 172 male and 231 female, with age ranging from 33 to 81 years (mean ± SD, 60.7 ± 9.3). The post-illumination pupil response (PIPR) was recorded using binocular infrared pupillometer (Neur-Optics, Inc., Irvine, CA). Cognitive testing consisted of Trail Making Test (TMT) Parts A and B, Rey Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), and Verbal Fluency Test (VFT) (F, A, and S). Principal component analysis (PCA) was used to calculate an overall cognitive function score. There was a significant reduction in the mean baseline pupil diameter by 0.21 mm for every 5-year increase in age (95% CI: -0.25, -0.17). There was also a significant increase in the PCA cognitive score by 0.20 (linear regression, 95% CI: 0.08, 0.32) for every 0.1 unit increase in the PIPR. The association remained significant after adjusting for age, sex, education, medications, systemic and ocular disease, and short form-12 physical and mental component score. The results of this study demonstrated a modest association between the PIPR and cognitive function, warranting longitudinal studies to evaluate the role of the PIPR in predicting cognitive function in the middle-aged and older adults.
| S-EPMC6607919 | biostudies-literature
Project description:Myopia, or nearsightedness, is the most common form of refractive abnormality and is characterized by excessive ocular elongation in relation to ocular power. Retinal neurotransmitter signaling, including dopamine, is implicated in myopic ocular growth, but the visual pathways that initiate and sustain myopia remain unclear. Melanopsin-expressing retinal ganglion cells (mRGCs), which detect light, are important for visual function, and have connections with retinal dopamine cells. Here, we investigated how mRGCs influence normal and myopic refractive development using two mutant mouse models: Opn4-/- mice that lack functional melanopsin photopigments and intrinsic mRGC responses but still receive other photoreceptor-mediated input to these cells; and Opn4DTA/DTA mice that lack intrinsic and photoreceptor-mediated mRGC responses due to mRGC cell death. In mice with intact vision or form-deprivation, we measured refractive error, ocular properties including axial length and corneal curvature, and the levels of retinal dopamine and its primary metabolite, L-3,4-dihydroxyphenylalanine (DOPAC). Myopia was measured as a myopic shift, or the difference in refractive error between the form-deprived and contralateral eyes. We found that Opn4-/- mice had altered normal refractive development compared to Opn4+/+ wildtype mice, starting ∼4D more myopic but developing ∼2D greater hyperopia by 16 weeks of age. Consistent with hyperopia at older ages, 16 week-old Opn4-/- mice also had shorter eyes compared to Opn4+/+ mice (3.34 vs 3.42 mm). Opn4DTA/DTA mice, however, were more hyperopic than both Opn4+/+ and Opn4-/- mice across development ending with even shorter axial lengths. Despite these differences, both Opn4-/- and Opn4DTA/DTA mice had ∼2D greater myopic shifts in response to form-deprivation compared to Opn4+/+ mice. Furthermore, when vision was intact, dopamine and DOPAC levels were similar between Opn4-/- and Opn4+/+ mice, but higher in Opn4DTA/DTA mice, which differed with age. However, form-deprivation reduced retinal dopamine and DOAPC by ∼20% in Opn4-/- compared to Opn4+/+ mice but did not affect retinal dopamine and DOPAC in Opn4DTA/DTA mice. Lastly, systemically treating Opn4-/- mice with the dopamine precursor L-DOPA reduced their form-deprivation myopia by half compared to non-treated mice. Collectively our findings show that disruption of retinal melanopsin signaling alters the rate and magnitude of normal refractive development, yields greater susceptibility to form-deprivation myopia, and changes dopamine signaling. Our results suggest that mRGCs participate in the eye's response to myopigenic stimuli, acting partly through dopaminergic mechanisms, and provide a potential therapeutic target underling myopia progression. We conclude that proper mRGC function is necessary for correct refractive development and protection from myopia progression.
| S-EPMC8792255 | biostudies-literature
Project description:Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin. These cells receive afferent inputs from rods and cones, which provide inputs to the postreceptoral visual pathways. It is unknown, however, how melanopsin activation is integrated with postreceptoral signals to control the pupillary light reflex. This study reports human flicker pupillary responses measured using stimuli generated with a five-primary photostimulator that selectively modulated melanopsin, rod, S-, M-, and L-cone excitations in isolation, or in combination to produce postreceptoral signals. We first analyzed the light adaptation behavior of melanopsin activation and rod and cones signals. Second, we determined how melanopsin is integrated with postreceptoral signals by testing with cone luminance, chromatic blue-yellow, and chromatic red-green stimuli that were processed by magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways, respectively. A combined rod and melanopsin response was also measured. The relative phase of the postreceptoral signals was varied with respect to the melanopsin phase. The results showed that light adaptation behavior for all conditions was weaker than typical Weber adaptation. Melanopsin activation combined linearly with luminance, S-cone, and rod inputs, suggesting the locus of integration with MC and KC signals was retinal. The melanopsin contribution to phasic pupil responses was lower than luminance contributions, but much higher than S-cone contributions. Chromatic red-green modulation interacted with melanopsin activation nonlinearly as described by a "winner-takes-all" process, suggesting the integration with PC signals might be mediated by a postretinal site.
| S-EPMC5054726 | biostudies-literature
Project description:Genome-wide association studies (GWAS) have dissected numerous genetic factors underlying refractive errors (RE) such as myopia. Despite significant insights into understanding the genetic architecture of RE, few studies have validated and explored the functional role of candidate genes within these loci. To functionally follow-up on GWAS and characterize the potential role of candidate genes on the development of RE, we prioritized nine genes (TJP2, PDE11A, SHISA6, LAMA2, LRRC4C, KCNQ5, GNB3, RBFOX1, and GRIA4) based on biological and statistical evidence; and used CRISPR/cas9 to generate knock-out zebrafish mutants. These mutant fish were screened for abnormalities in axial length by spectral-domain optical coherence tomography and refractive status by eccentric photorefraction at the juvenile (2 months) and adult (4 months) developmental stage. We found a significantly increased axial length and myopic shift in refractive status in three of our studied mutants, indicating a potential involvement of the human orthologs (LAMA2, LRRC4C, and KCNQ5) in myopia development. Further, in-situ hybridization studies showed that all three genes are expressed throughout the zebrafish retina. Our zebrafish models provide evidence of a functional role of these three genes in refractive error development and offer opportunities to elucidate pathways driving the retina-to-sclera signaling cascade that leads to myopia.
| S-EPMC9898536 | biostudies-literature
Project description:NEI Refractive Error Collaboration (KORA)
| PRJNA75817 | ENA
Project description:The human pupillary light response is driven by all classes of photoreceptors in the human eye-the three classes of cones, the rods, and the intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin. These photoreceptor classes have distinct but overlapping spectral tuning, and even a monochromatic light with a wavelength matched to the peak spectral sensitivity of a given photoreceptor will stimulate all photoreceptors. The method of silent substitution uses pairs of lights ("metamers") to selectively stimulate a given class of photoreceptors while keeping the activation of all others constant. In this primer, we describe the method of silent substitution and provide an overview of studies that have used it to examine inputs to the human pupillary light response.
| S-EPMC6277556 | biostudies-literature