IMPAIRED DARK ADAPTATION ASSOCIATED WITH A DISEASED BRUCH MEMBRANE IN PSEUDOXANTHOMA ELASTICUM.

PURPOSE: To characterize dark adaptation in patients with pseudoxanthoma elasticum, a systemic disease leading to calcification of elastic tissue including the Bruch membrane. METHODS: In this prospective case-control study, dark adaptation thresholds were measured using a Goldmann-Weekers dark adaptometer. Additional assessments included best-corrected visual acuity testing, contrast sensitivity, low luminance deficit, and vision-related quality of life. RESULTS: Dark adaptation thresholds were significantly higher, and adaptation periods were prolonged in patients with pseudoxanthoma elasticum (n = 35; 33 with 2 ABCC6 mutations) compared with controls (n = 35). The time to adapt 4 log units (20.6 ± 8.6 vs. 8.0 ± 1.3 minutes) and the mean dark adaptation threshold after 15 minutes (3.5 ± 1.1 vs. 1.8 ± 0.2 log units) were significantly different between patients and controls (both P < 0.001). Low luminance deficits (12.3 ± 6.4 vs. 6.1 ± 4.3 ETDRS letters), contrast sensitivity (1.4 ± 0.3 vs. 1.9 ± 0.1), and low luminance-related quality of life (LLQ score: 1,286 ± 355 vs. 2,167 ± 68) were also significantly worse in patients with pseudoxanthoma elasticum (all, P < 0.001). Two patients were treated with high-dose vitamin A which partially reversed impaired dark adaptation. CONCLUSION: Patients with pseudoxanthoma elasticum often have impaired dark adaptation. Positive effects of vitamin A supplementation may indicate restricted retinal access of vitamin A through the Bruch membrane as one possible underlying pathogenic factor.

Blast-induced brain injury in rats leads to transient vestibulomotor deficits and persistent orofacial pain.

Blast-induced traumatic brain injury (blast-TBI) is associated with vestibulomotor dysfunction, persistent post-traumatic headaches and post-traumatic stress disorder, requiring extensive treatments and reducing quality-of-life. Treatment and prevention of these devastating outcomes require an understanding of their underlying pathophysiology through studies that take advantage of animal models. Here, we report that cranium-directed blast-TBI in rats results in signs of pain that last at least 8 weeks after injury. These occur without significantly elevated behavioural markers of anxiety-like conditions and are not associated with glial up-regulation in sensory thalamic nuclei. These injuries also produce transient vestibulomotor abnormalities that resolve within 3 weeks of injury. Thus, blast-TBI in rats recapitulates aspects of the human condition.

Low-Level Nighttime Light Therapy for Age-Related Macular Degeneration: A Randomized Clinical Trial.

Purpose: To investigate the safety, acceptability, and effectiveness of light therapy on the progression of AMD over 12 months. Methods: This was a phase I/IIa, prospective, proof-of-concept, single-center, unmasked randomized controlled trial. Sixty participants (55 to 88 years) with early AMD in the study eye and neovascular AMD (nAMD) in the fellow eye were recruited from a hospital nAMD clinic. Eligible participants were randomized (ratio 1:1) to receive light therapy or to an untreated control group. Light therapy was delivered via a light-emitting mask (peak 505 nm, 23 scotopic Td), which was worn each night for 12 months. Co-primary outcome measures were disease progression (onset of nAMD or increased drusen volume beyond test-retest limits) and change in time constant of cone dark adaptation. Other main outcomes included adverse events, compliance, and subjective sleep quality data. Results: Disease progression over 12 months was seen in 38.1% (18.1%-61.6% confidence interval [CI]) of intervention participants and 48.3% (29.4%-67.5% CI) of controls (Mantel-Haenszel test, common odds ratio = 0.763, P = 0.495). A significantly larger delay in cone adaptation was observed in the intervention group (1.66 ± 0.61 minutes) than in the control group (0.66 ± 0.49 minutes) over the follow-up period. No reported adverse events were deemed to be associated with the intervention. Conclusions: Although acceptable to the patients, light therapy did not have a substantial effect on the progression of early AMD over 12 months. Further investigation is necessary to discover the permanency and cause of the adverse effect of light therapy on dark adaptation.

HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

PURPOSE: To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). METHODS: Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. RESULTS: Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; ß = 0.30, P = 0.045), taking AREDS vitamins (ß = 5.51, P < 0.001), and family history of AMD (ß = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (ß = 1.84, P = 0.006), taking AREDS supplements (ß = 1.67, P = 0.021) and alcohol intake (ß = 0.07, P = 0.017). CONCLUSION: Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

Light-Dark Adaptation of Channelrhodopsin Involves Photoconversion between the all-trans and 13-cis Retinal Isomers.

Channelrhodopsins (ChR) are light-gated ion channels of green algae that are widely used to probe the function of neuronal cells with light. Most ChRs show a substantial reduction in photocurrents during illumination, a process named "light adaptation". The main objective of this spectroscopic study was to elucidate the molecular processes associated with light-dark adaptation. Here we show by liquid and solid-state nuclear magnetic resonance spectroscopy that the retinal chromophore of fully dark-adapted ChR is exclusively in an all-trans configuration. Resonance Raman (RR) spectroscopy, however, revealed that already low light intensities establish a photostationary equilibrium between all-trans,15-anti and 13-cis,15-syn configurations at a ratio of 3:1. The underlying photoreactions involve simultaneous isomerization of the C(13)═C(14) and C(15)═N bonds. Both isomers of this DAapp state may run through photoinduced reaction cycles initiated by photoisomerization of only the C(13)═C(14) bond. RR spectroscopic experiments further demonstrated that photoinduced conversion of the apparent dark-adapted (DAapp) state to the photocycle intermediates P500 and P390 is distinctly more efficient for the all-trans isomer than for the 13-cis isomer, possibly because of different chromophore-water interactions. Our data demonstrating two complementary photocycles of the DAapp isomers are fully consistent with the existence of two conducting states that vary in quantitative relation during light-dark adaptation, as suggested previously by electrical measurements.

Using Flickering Light to Enhance Nonimage-Forming Visual Stimulation in Humans.

PURPOSE: Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate nonimage-forming visual functions such as pupillary constriction and circadian photoentrainment. Optimizing daytime nonimage-forming photostimulation has health benefits. We aimed to enhance ipRGC excitation using flickering instead of steady light. METHODS: Human subjects were tested with a three-dimensional matrix of flickering 463-nm stimuli: three photon counts (13.7, 14.7 and 15.7 log photons cm(-2)), three duty cycles (12%, 47%, and 93%) and seven flicker frequencies (0.1, 0.25, 0.5, 1, 2, 4, and 7 Hz). Steady-state pupil constrictions were measured. RESULTS: Among stimuli containing 13.7 log photons cm-2, the one flickering at 2 Hz with a 12% duty cycle evoked the greatest pupil constriction of 48% ± 4%, 71% greater than that evoked by an equal-intensity (12.3 log photons cm(-2) s(-1)) continuous light. This frequency and duty cycle were also best for 14.7 log photons cm-2 stimuli, inducing a 58% ± 4% constriction which was 38% more than that caused by an equal-intensity (13.3 log photons cm(-2) s(-1)) constant light. For 15.7 log photons cm-2 stimuli, the 1-Hz, 47% duty cycle flicker was optimal although it evoked the same constriction as the best 14.7 log photons cm(-2) flicker. CONCLUSIONS: Pupillary constriction depends on flicker frequency and duty cycle besides intensity. Among the stimuli tested, the one with the lowest photon count inducing a maximal response is 13.3 log photons cm(-2) s(-1) flickering at 2 Hz with 12% duty cycle. Our data could guide the design of healthier architectural lighting and better phototherapy devices for treating seasonal affective disorder and jet lag.

A pilot study of an acupuncture protocol to improve visual function in retinitis pigmentosa patients.

BACKGROUND: Patients with retinitis pigmentosa are motivated to try complementary or integrative therapies to slow disease progression. Basic science, clinical research and retinitis pigmentosa patients' self-reports support the hypothesis that acupuncture may improve visual function. METHODS: A prospective, case series, pilot study enrolled 12 adult patients with RP treated at an academic medical centre with a standardised protocol that combined electroacupuncture to the forehead and below the eyes and acupuncture to the body, at 10 half-hour sessions over two weeks. Pre- and post-treatment tests included Early Treatment Diabetic Retinopathy Study visual acuity (VA), Pelli-Robson contrast sensitivity (CS), Goldmann visual fields, and dark-adapted full-field stimulus threshold (FST)(n = 9). Scotopic Sensitivity Tester-1 (SST-1) dark-adaptometry was performed on the last two subjects. RESULTS: Six of 12 subjects had measurable, significant visual function improvements after treatment. Three of nine subjects tested with the FST had a significant 10.3 to 17.5 dB (that is, 13- to 53-fold) improvement in both eyes at one week after acupuncture, maintained for at least 10 to 12 months, which was well outside typical test-retest variability (95% CI: 3-3.5 dB) previously found in retinitis pigmentosa. SST-1 dark-adaptation was shortened in both subjects tested on average by 48.5 per cent at one week (range 36 to 62 per cent across 10 to 30 dB), which was outside typical coefficients of variation of less than 30 per cent previously determined in patients with retinitis pigmentosa and normals. Four of the five subjects with psychophysically measured scotopic sensitivity improvements reported subjective improvements in vision at night or in dark environments. One subject had 0.2 logMAR improvement in VA; another had 0.55 logCS improvement. Another subject developed more than 20 per cent improvement in the area of the Goldmann visual fields. The acupuncture protocol was completed and well tolerated by all, without adverse events or visual loss. CONCLUSIONS: Acupuncture entails minimal risk, if administered by a well-trained acupuncturist and may have significant, measurable benefits on residual visual function in patients with retinitis pigmentosa, in particular scotopic sensitivity, which had not previously been studied. These preliminary findings support the need for future controlled studies of potential mechanisms.

Neuronal nonlinearity explains greater visual spatial resolution for darks than lights.

Astronomers and physicists noticed centuries ago that visual spatial resolution is higher for dark than light stimuli, but the neuronal mechanisms for this perceptual asymmetry remain unknown. Here we demonstrate that the asymmetry is caused by a neuronal nonlinearity in the early visual pathway. We show that neurons driven by darks (OFF neurons) increase their responses roughly linearly with luminance decrements, independent of the background luminance. However, neurons driven by lights (ON neurons) saturate their responses with small increases in luminance and need bright backgrounds to approach the linearity of OFF neurons. We show that, as a consequence of this difference in linearity, receptive fields are larger in ON than OFF thalamic neurons, and cortical neurons are more strongly driven by darks than lights at low spatial frequencies. This ON/OFF asymmetry in linearity could be demonstrated in the visual cortex of cats, monkeys, and humans and in the cat visual thalamus. Furthermore, in the cat visual thalamus, we show that the neuronal nonlinearity is present at the ON receptive field center of ON-center neurons and ON receptive field surround of OFF-center neurons, suggesting an origin at the level of the photoreceptor. These results demonstrate a fundamental difference in visual processing between ON and OFF channels and reveal a competitive advantage for OFF neurons over ON neurons at low spatial frequencies, which could be important during cortical development when retinal images are blurred by immature optics in infant eyes.

Intravitreal silicon-based quantum dots as neuroprotective factors in a model of retinal photoreceptor degeneration.

PURPOSE: To study the intravitreal application of silicon quantum dots (QDs) and their capabilities to deliver electrical stimulation to the retinal cells and to assess the potential effect on retinal electrophysiology and anatomy. METHODS: A Royal College of Surgeon rat model of retinal degeneration was used in this study. A total of 32 eyes were used, divided in four groups of 8 eyes each; the first group received the silicon-based QD, the second group received an inactive gold-based QD, the third group received a sham injection, and the fourth group was used as a control. An electroretinogram (ERG) was done at baseline and thereafter every week for 9 weeks. At the end of the follow-up, eyes were collected for further pathologic analysis and nuclei cell counts. RESULTS: Eyes within the silicon-based QD group showed a definite but transient increase in the waves of the ERG, especially in the rod response compared with the sham and control groups (P < 0.05). The pathologic examination demonstrated a higher nuclei count in the QD group, consistent with a higher cell survival rate than that in the sham and control groups in which cells degenerated as expected. CONCLUSIONS: Intravitreal injection of silicon-based QD seems to be safe and well tolerated, with no evident toxic reaction and demonstrates a beneficial effect by prolonging cell survival rate and improving ERG patterns in a well-established model of retinal degeneration. (ClinicalTrials.gov numbers NCT00407602, NCT01490827.).

Evaluation of extended release brimonidine intravitreal device in normotensive rabbit eyes.

PURPOSE: To evaluate the safety profile of a brimonidine extended release intravitreal implant, in normotensive rabbit eyes. METHODS: Devices were made from hollow poly-l-lactic acid (PLA) tubes and contained hundred micrograms of brimonidine pamoate. Device was injected intravitreally in one eye of 12 New Zealand pigmented rabbits, whereas other eye was injected with a sham implant in masked fashion. Ocular examination was conducted at baseline and months 1, 3 and 6 including dilated fundus examination and electro-retinogram (ERG). Four rabbits were sacrificed at each time-point for retinal histology. ERG data were compared between groups and time-points using anova. RESULTS: No complications were reported from either eye of any rabbits over a 6-month period. Photopic A wave was reduced in the control eye at 1 month compared with baseline (p < 0.01). There was no significant difference in other ERG parameters between the groups at different time-points. Gross retinal histology was normal at all time-points. CONCLUSION: Extended release intravitreal brimonidine device was found to be safe and in normotensive rabbit eyes.

Regression of early diabetic macular oedema is associated with prevention of dark adaptation.

HYPOTHESIS: Dark-adapted rods consume oxygen at high rates and light adaptation decreases this oxygen burden and can have therapeutic effects on diabetic macular oedema (DMO). METHODS: Patients with mild non-proliferative diabetic retinopathy (DR) and early, untreated non-sight-threatening DMO slept for 6 months wearing masks that illuminated the eyelid of one closed eye by 505 nm light. Exclusion criteria were any concomitant eye disease, DR >ETDRS grade 35, and other systemic diseases. PRIMARY OUTCOME: change of OCT retinal thickness in the local region where oedema was present. RESULTS: A total of 34 out of 40 patients completed the study. Mean baseline OCT macular cube thickness was equivalent for study and fellow eyes. But study eyes had a greater mean thickness in the central subfield zone 1 (282±53 µm) vs (256±19 µm) the fellow eyes. Twenty-eight study eyes showed intraretinal cysts compared with nine in the fellow eyes. At 6 months, only 19 study eyes had cysts while cysts were seen in 20 fellow eyes. After 6 months, the worst affected ETDRS zone and the central subfield zone 1 reduced in thickness in study eyes only by 12 µm (95% CI 20 to -7, P=0.01). The secondary outcomes of change in visual acuity, achromatic contrast sensitivity, and microperimetric thresholds improved significantly in study eyes and deteriorated in fellow eyes. CONCLUSIONS: Sleeping in dim light that can keep rods light adapted may reverse the changes of DMO.

Maternal dietary loads of α-tocopherol differentially influence fear conditioning and spatial learning in adult offspring.

α-Tocopherol, the main component of vitamin E, is well known to be a radical scavenger, so an increased intake of vitamin E is recommended in complicated pregnancy, to prevent possible fetus damage by free radical. In a previous work, we found that maternal α-tocopherol supplementation affects PKC-mediated cellular signaling and hippocampal synaptic plasticity in developing brain; the latter effect persists in adulthood. Here, adult rats maternally exposed to supranutritional doses of α-tocopherol were evaluated for Contextual Fear Conditioning and spatial learning in Morris Water Maze, two different hippocampus-dependent learning tasks. Moreover, anxiety, spontaneous activity, and explorative drive were also evaluated as factors potentially affecting learning performance. Treated rats showed a different behavior with respect to controls: performance in Contextual Fear Conditioning was improved, while spatial learning tested in Morris Water Maze, was impaired. The improvement of fear response was not ascribable to differences in anxiety level and/or spontaneous activity; thus it appears to be a specific effect of α-tocopherol overloading during brain development. On the contrary, the impaired performance in Morris Water Maze exhibited by treated rats can be in part explained by their enhanced explorative drive. Although extrapolation from rats to humans is difficult, a caveat in assuming supranutritional doses of vitamin E in pregnancy arises from this study.

Inflammation modulates anxiety in an animal model of multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by inflammation, but also degenerative changes. Besides neurological deficits, the rate of affective disorders such as depression and anxiety is at least six fold increased. Many aspects of MS can be mimicked in the animal model of myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (MOG-EAE). Here we investigate behavioral changes in C57BL/6 mice suffering from mild MOG-EAE. In the later phase of the disease, mice were subjected to behavioral tests including the light-dark-box (LD Box), the acoustic startle response (SR) with a pre-pulse inhibition protocol as well as the learned helplessness (LH) paradigm. Behavioral data were correlated with the motor performance in an open field and rotarod test (RR). In the RR and open field, there was no significant difference in the motor performance between controls and mice suffering from mild MOG-EAE. Yet EAE mice displayed an increased anxiety-like behavior with a 23% reduction of the time spent in the bright compartment of the LD Box as well as an increased SR. In the LH paradigm, mice suffering from MOG-EAE were twice as much prone to depressive-like behavior. These changes correlate with an increase of hippocampal tissue tumor necrosis factor alpha levels and neuronal loss in the hippocampus. Modulation of monoaminergic transmission by chronic application of the antidepressant amitriptyline resulted in a decreased startle reaction and increased hippocampal norepinephrine levels. These data imply that chronic inflammation in the CNS may impact on emotional responses in rodent models of anxiety.

Adaptações fisiológicas e anatômicas de melissa officinalis L. (Lamiaceae) cultivadas sob malhas termorrefletoras em diferentes intensidades luminosas / Physiological and morphological adaptations of melissa officinalis L. (Lamiaceae) cultivated under thermo-reflector shading nets at different luminous intensities

Objetivou-se, com a realização da pesquisa, avaliar modificações fisiológicas e anatômicas em plantas de melissa, cultivadas sob malhas termorrefletoras (Aluminet®), em diferentes níveis de sombreamento, visando conhecer a plasticidade fenotípica em resposta de adaptação a diferentes quantidades de luz. Os tratamentos foram caracterizados por plantas submetidas a pleno sol e a 20 e 60 por cento de intensidade luminosa, e arranjados conforme o delineamento inteiramente casualizado (DIC). As quantificações de clorofila foram feitas em quatro repetições, as medições das epidermes e parênquimas foram repetidas 15 vezes e utilizou-se 10 repetições para as avaliações das características de cloroplastos e grãos de amido destes. Plantas submetidas a 20 por cento de intensidade luminosa apresentaram maior quantidade de clorofila a e, portanto, maior razão clorofila a/b. Comparativamente, as folhas de melissa a pleno sol e a 60 por cento de luz apresentaram células da epiderme adaxial mais espessas, mas as células da epiderme abaxial mostraram características encontradas em folhas de sombra, ou seja, mais finas. Quanto maior a intensidade luminosa, maior o número de cloroplastos, porém, a pleno sol mostraram-se mais finos e com menor área. Os grãos de amido de plantas cultivadas sob ambientes sombreados tiveram maior área e ocuparam maior parte nos cloroplastos de plantas a 60 por cento de intensidade luminosa. Assim, plantas de melissa, quando submetidas ao sombreamento, tiveram plasticidade fenotípica.

The aim of this study was to evaluate physiological and anatomical modifications in lemon balm plants, cultivated under thermo-reflector nets (Aluminet®) at different levels of shading, in order to understand the phenotypic plasticity in adaptation response to different light quantities. The treatments were characterized by plants subjected to full sun and 20 and 60 percent of luminous intensity, and arranged in completely randomized design (CRD). The quantifications of chlorophylls were done in four replicates, the measurements of epidermis and parenchymas were repeated 15 times and 10 replicates were used to evaluate characteristics of chloroplasts and their starch grains. Plants subjected to 20 percent of luminous intensity showed higher quantity of chlorophyll a and, therefore, higher chlorophyll a/b ratio. Lemon balm leaves under full sun and 60 percent of light showed thicker adaxial epidermis cells, but the abaxial epidermis cells showed characteristics found in shaded leaves, i.e., they were slender. The higher the light intensity, the larger the number of chloroplasts; however, under full sun, they were slender and had smaller area. The starch grains of leaves grown under shaded environments showed larger area and, at 60 percent of luminous intensity, occupied the largest part of chloroplasts. Thus, lemon balm plants, subjected to shading conditions, showed phenotypic plasticity.

Adaptive changes in firing of primary auditory cortical neurons following illumination shift from light to dark in freely moving guinea pigs.

Some animals are forced to rely more on non-visual signals, such as audition or olfaction, than on vision when a bright environment becomes dark. By recording from a primary-like auditory cortex (field A) in freely moving guinea pigs, possible changes in the responsiveness of single units were explored in association with illumination changes. For a subset of units, we found that robust decreases (off-decrease) or increases (off-increase) in baseline discharge (BsD) were initiated soon after room light was silently extinguished. These neuronal changes were accompanied by the initiation of explorative locomotion, possibly reflecting a changed internal brain state. Preferred acoustic stimuli evoked salient excitatory responses against the reduced BsD level in the dark for the off-decrease units, and salient inhibitory responses against the increased BsD level for the off-increase units. Histological verification indicated that the units showing such BsD changes were located predominantly in layer V or its vicinity. These results are discussed in the context of the effects of the brainstem neuromodulatory systems that are activated during behavioral adaptation to new environments.

Sleep and sleep homeostasis in constant darkness in the rat.

According to the two-process model of sleep regulation, a homeostatic Process S increases during waking and decreases during sleep. The time course of Process S can be derived on the basis of changes in vigilance states and changes in electroencephalogram slow-wave activity (SWA, activity below 4 Hz) during non-rapid eye movement (NREM) sleep. In most mouse strains, an optimal fit between S and SWA was achieved with one increasing (active during waking and REM sleep) and one decreasing time constant (active during NREM sleep) for Process S. However, in the rat, systematic deviations in the light and dark periods were observed, which were resolved by introducing different decreasing time constants between the light and dark periods. The present study shows that this difference between the rest (light) and active (dark) phases remains, and may even be larger, after animals are adapted to constant dark conditions for at least a week. In addition, the data show that the build-up rate of SWA at the onset of a NREM sleep episode is slow compared with the increase rate under light-dark conditions, and that this build-up rate changes with the circadian phase. The slow build-up rate introduces a systematic error between the simulation of Process S and SWA in NREM sleep. The circadian modulation of the build-up rate may, together with circadian changes in NREM sleep episode duration, be the source of the necessity of introducing a difference in the decreasing time constant between the rest and active phases.

Impact of light therapy on rod and cone functions in healthy subjects.

Light therapy is an effective treatment for patients with seasonal affective disorders and is commonly used at an intensity of 10,000 lx. The aim of this study was to investigate the direct impact of light therapy on cones and rods photoreceptors using the electroretinogram (ERG) technique. Twelve healthy subjects were exposed for 60 min to three light conditions: 10,000 lx, 100 lx and 5 lx. ERG cone and rod luminance response functions were obtained immediately after exposures. Cone function was not affected by any light conditions. Maximal response achieved by the rods was significantly lower following the 100 lx and 10,000 lx conditions when compared with the 5 lx condition. Retinal rod sensitivity was significantly lower in the 10,000 lx condition when compared with the 12 lx condition. A decrease in rod function can readily be observed at 100 lx, that is, at regular indoor lighting. This decrease could be related to the triggering of retinal dopamine production, which would favour day vision over night vision. The further decrease in light sensitivity observed after 60 min at 10,000 lx may be perceived as a protective mechanism of the rod system against bright light.

Effect of short-term, high-dose retinol on dark adaptation in aging and early age-related maculopathy.

PURPOSE: To examine the effect of a short course of high-dose retinol (preformed vitamin A) on dark adaptation in older adults with normal retinal health or early age-related maculopathy (ARM). METHODS: The study design was a randomized, double-masked, placebo-controlled experiment. Adults > or = 50 years of age whose fundus photographs for the eye to be tested psychophysically fell within steps 1 to 9 of the Age-Related Eye Disease Study (AREDS) Grading System were randomly assigned to a 30-day course of 50,000 IU oral retinol or a placebo. At baseline and 30-day follow-up, dark adaptation was tested and the Low Luminance Questionnaire (LLQ), an instrument for assessing difficulty with vision in reduced lighting, was administered. Primary outcomes of interest were rod- and cone-mediated parameters of dark adaptation, with scores on the LLQ's six subscales as secondary outcomes. RESULTS: The sample consisted of 104 participants with 52 each in the intervention and placebo groups. There were no group differences in baseline variables. At 30-days, the dark-adaptation parameters of cone time-constant, cone threshold, rod-cone break, and rod threshold did not differ. The retinol intervention group had significantly larger (i.e., steeper) rod slopes, indicating faster sensitivity recovery, than did the placebo group (P = 0.0419). There were no group differences in scores on the LLQ subscales driving, extreme lighting, emotional distress, general lighting, or peripheral vision. The retinol group had a higher score by five points on the mobility subscale compared with the placebo group (P = 0.0141). Those who had the most self-reported change on the mobility subscale at day 30 were more likely to have greater change in the speed of dark adaptation, as indicated by the rod slope parameter (r = 0.24, P = 0.0141). CONCLUSIONS: A short-term, high-dose course of retinol increased the rate of rod-mediated dark adaptation in older adults who were in the early phases of ARM or were exhibiting normal retinal aging. These results are consistent with the hypothesis that depositions and other structural changes in the retinal pigment epithelium and Bruch's membrane in aging and early ARM cause a localized retinoid deficiency.