Effect of the chromaticity of stimuli on night vision disturbances.

The perception of halos and other night vision disturbances is a common complaint in clinical practice. Such visual disturbances must be assessed in order to fully characterize each patient's visual performance, which is particularly relevant when carrying out a range of daily tasks. Visual problems are usually assessed using achromatic stimuli, yet the stimuli encountered in daily life have very different chromaticities. Hence, it is important to assess the effect of the chromaticity of visual stimuli on night vision disturbances. The aim of this work is to study the influence of the chromaticity of different visual stimuli on night vision disturbances by analyzing straylight and visual discrimination under low-light conditions. For that, we assessed the monocular and binocular visual discrimination of 27 subjects under low illumination using the Halo test. The subjects' visual discrimination was assessed after exposure to different visual stimuli: achromatic, red, green, and blue, both at the monitor's maximum luminance and maintaining the same luminance value for the different visual stimuli. Monocular straylight was also measured for an achromatic, red, green, and blue stimuli. The blue stimulus had the greatest effect on halos in both monocular and binocular conditions. Visual discrimination was similar for the red, green, and achromatic stimuli, but worsened at lower luminance. The greatest influence of straylight was observed for the blue stimulus. In addition, visual discrimination correlated with straylight measurements for achromatic stimuli, wherein greater straylight values correlated with an increased perception of halos and other visual disturbances.

Spatially Resolved Association of Structural Biomarkers on Retinal Function in Non-Exudative Age-Related Macular Degeneration Over 4 Years.

Purpose: To longitudinally assess the impact of high-risk structural biomarkers for natural disease progression in non-exudative age-related macular degeneration (AMD) on spatially resolved mesopic and scotopic fundus-controlled perimetry testing. Methods: Multimodal retinal imaging data and fundus-controlled perimetry stimuli points were semiautomatically registered according to landmark correspondences at each annual visit over a period of up to 4 years. The presence of sub-RPE drusen, subretinal drusenoid deposits, pigment epithelium detachments (PEDs), hyper-reflective foci (HRF), vitelliform lesions, refractile deposits, and incomplete RPE and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) were graded at each stimulus position and visit. Localized retinal layer thicknesses were extracted. Mixed-effect models were used for structure-function correlation. Results: Fifty-four eyes of 49 patients with non-exudative AMD (mean age, 70.7 ± 9.1 years) and 27 eyes of 27 healthy controls (mean age, 63.4 ± 8.9 years) were included. During study course, presence of PED had the highest functional impact with a mean estimated loss of -1.30 dB (P < 0.001) for mesopic and -1.23 dB (P < 0.001) for scotopic testing, followed by HRF with -0.89 dB (mesopic, P = 0.001) and -0.87 dB (scotopic, P = 0.005). Subretinal drusenoid deposits were associated with a stronger visual impairment (mesopic, -0.38 dB; P = 0.128; scotopic, -0.37 dB; P = 0.172) compared with sub-RPE drusen (-0.22 dB, P = 0.0004; -0.18 dB, P = 0.006). With development of c-RORA, scotopic retinal sensitivity further significantly decreased (-2.15 dB; P = 0.02). Thickening of the RPE-drusen-complex and thinning of the outer nuclear layer negatively impacted spatially resolved retinal sensitivity. Conclusions: The presence of PED and HRF had the greatest prognostic impact on progressive point-wise sensitivity losses. Higher predominant rod than cone-mediated localized retinal sensitivity losses with early signs of retinal atrophy development indicate photoreceptor preservation as a potential therapeutic target for future interventional AMD trials.

Convergent mechanism underlying the acquisition of vertebrate scotopic vision.

High sensitivity of scotopic vision (vision in dim light conditions) is achieved by the rods' low background noise, which is attributed to a much lower thermal activation rate (kth) of rhodopsin compared with cone pigments. Frogs and nocturnal geckos uniquely possess atypical rods containing noncanonical cone pigments that exhibit low kth, mimicking rhodopsin. Here, we investigated the convergent mechanism underlying the low kth of rhodopsins and noncanonical cone pigments. Our biochemical analysis revealed that the kth of canonical cone pigments depends on their absorption maximum (λmax). However, rhodopsin and noncanonical cone pigments showed a substantially lower kth than predicted from the λmax dependency. Given that the λmax is inversely proportional to the activation energy of the pigments in the Hinshelwood distribution-based model, our findings suggest that rhodopsin and noncanonical cone pigments have convergently acquired low frequency of spontaneous-activation attempts, including thermal fluctuations of the protein moiety, in the molecular evolutionary processes from canonical cone pigments, which contributes to highly sensitive scotopic vision.

The role of visual conditions and aircraft type on different aspects of pilot workload.

OBJECTIVE: The objective of our work was to assess the impact of flight conditions by aircraft type on the workload estimated using NASA-Task Load Index (NASA-TLX). BACKGROUND: Learning about subjective workload is important for assessing the impact of a pilot's work environment on their performance in the cockpit. This is an important element of flight safety and includes the prevention of aviation accidents. METHODS: The study included 146 military pilots that fly the following aircrafts: flying fast-jet (21), fixed-wing (24), and rotary-wing (101). The NASA-TLX questionnaire was used to assess workload and pilots were asked to determine the level of workload resulting from flying under the following conditions: daytime flight (VFR), night-vision flight performed under Night Visual Flight Rules (NVFR), and night-vision flight using night-vision goggles (NVGs). RESULTS: The highest level of workload was consistently attributed to flights performed under NVG conditions. NVFR conditions were rated as the most burdensome, while VFR conditions were rated as the least burdensome. Fast-jet pilots rated their mental performance and effort workload as significantly higher than pilots of other aircrafts. CONCLUSION: Pilots' perceived workload is influenced by both flight conditions and the type of aircraft they fly. Workload knowledge is important for flight safety and should be taken into account during training and flight-task planning. APPLICATION: The results of our study can be useful both in flight training and in work on the effectiveness of the human-machine interface. Awareness of one's own limitations due to the work environment can help improve flight safety.

Visual function correlates of self-reported vision-related nighttime driving difficulties.

PURPOSE: To investigate the visual function correlates of self-reported vision-related night driving difficulties among drivers. METHODS: One hundred and seven drivers (age: 46.06 ± 8.24, visual acuity [VA] of 0.2logMAR or better) were included in the study. A standard vision and night driving questionnaire (VND-Q) was administered. VA and contrast sensitivity were measured under photopic and mesopic conditions. Mesopic VA was remeasured after introducing a peripheral glare source into the participants' field of view to enable computation of disability glare index. Regression analyses were used to assess the associations between VND-Q scores, and visual function measures. RESULTS: The mean VND-Q score was -3.96±1.95 logit (interval scale score: 2.46±1.28). Simple linear regression models for photopic contrast sensitivity, mesopic VA, mesopic contrast sensitivity, and disability index significantly predicted VND-Q score (P<0.05), with mesopic VA and disability glare index accounting for the greatest variation (21 %) in VND-Q scores followed by photopic contrast sensitivity (19 %), and mesopic contrast sensitivity (15 %). A multiple regression model to determine the association between the predictors (photopic contrast sensitivity, mesopic VA, mesopic contrast sensitivity, and disability index) and VND-Q score yielded significant results, F (4, 102) = 8.58, P < 0.001, adj. R2 = 0.2224. Seeing dark-colored cars was the most challenging vision task. CONCLUSION: Changes in mesopic visual acuity, photopic and mesopic contrast sensitivity, as well as disability glare index are associated with and explain night driving-related visual difficulties. It is recommended to incorporate measurement of these visual functions into assessments related to driving performance.

Facial Fracture Injury Criteria from Night Vision Goggle Impact.

INTRODUCTION: Military personnel extensively use night vision goggles (NVGs) in contemporary scenarios. Since NVGs may induce or increase injuries from falls or vehicular accidents, biomechanical risk assessments would aid design goal or mitigation strategy development.METHODS: This study assesses injury risks from NVG impact on cadaver heads using impactors modeled on the PVS-14 NVG. Impacts to the zygoma and maxilla were performed at 20° or 40° angles. Risks of facial fracture, neurotrauma, and neck injury were assessed. Acoustic sensors and accelerometers assessed time of fracture and provided input variables for injury risk functions. Injuries were assessed using the Abbreviated Injury Scale (AIS); injury severity was assessed using the Rhee and Donat scales. Risk functions were developed for the input variables using censored survival analyses.RESULTS: The effects of impact angle and bone geometry on injury characteristics were determined with loading area, axial force, energy attenuation, and stress at fracture. Probabilities of facial fracture were quantified through survival analysis and injury risk functions. These risk functions determined a 50% risk of facial bone fracture at 1148 N (axial force) at a 20° maxillary impact, 588 N at a 40° maxillary impact, and 677 N at a 20° zygomatic impact. A cumulative distribution function indicates 769 N corresponds to 50% risk of fracture overall.DISCUSSION: Results found smaller impact areas on the maxilla are correlated with higher angles of impact increasing risk of facial fracture, neck injuries are unlikely to occur before fracture or neurotrauma, and a potential trade-off mechanism between fracture and brain injury.Davis MB, Pang DY, Herring IP, Bass CR. Facial fracture injury criteria from night vision goggle impact. Aerosp Med Hum Perform. 2023; 94(11):827-834.

Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice.

Interphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visual function for demanding visual tasks was assessed in IRBP knock-out (KO) mice. Surprisingly, IRBP KO mice showed no differences in scotopic critical flicker frequency (CFF) compared to wildtype (WT). However, they did have lower photopic CFF than WT. IRBP KO mice had reduced scotopic and photopic acuity and contrast sensitivity compared to WT. IRBP KO mice had a significant reduction in outer nuclear layer (ONL) thickness, PR outer and inner segment, and full retinal thickness (FRT) compared to WT. There were fewer cones in IRBP KO mice. Overall, these results confirm substantial loss of rods and significant loss of cones within 30 days. Absence of IRBP resulted in cone circuit damage, reducing photopic flicker, contrast sensitivity, and spatial frequency sensitivity. The c-wave was reduced and accelerated in response to bright steps of light. This result also suggests altered retinal pigment epithelium activity. There appears to be a compensatory mechanism such as higher synaptic gain between PRs and bipolar cells since the loss of the b-wave did not linearly follow the loss of rods, or the a-wave. Scotopic CFF is normal despite thinning of ONL and reduced scotopic electroretinogram (ERG) in IRBP KO mice, suggesting either a redundancy or plasticity in circuits detecting (encoding) scotopic flicker at threshold even with substantial rod loss.

Increased Metabolic Demand During Outside Walking in Darkness With No Vision or With Visual Aid.

INTRODUCTION: For tactical reasons, the foot-borne soldiers sometimes undertake nighttime operations. However, the metabolic demand during walking in complete darkness may be markedly increased. The purpose of this study was to investigate if metabolic demand and kinematics would change while walking on a gravel road and a slightly hilly trail in darkness with or without visual aid. MATERIALS AND METHODS: Fourteen cadets (11 men and 3 women, age: 25 ± 7 years, height: 178 ± 8 cm, and weight: 78 ± 13 kg) walked at 4 km/h on a straight gravel road and on a slightly hilly forest trail (n = 9). Both trials were performed at nighttime under four different conditions, wearing a headlamp (Light), blindfold (Dark), monocular (Mono), or binocular (Bino) night vision goggles. During the 10-minute walks, oxygen uptake, heart rate, and kinematic data were assessed. Ratings of perceived exertion, discomfort, and mental stress were evaluated after each condition using a category ratio scale. Physiologic and kinematic variables were evaluated using repeated-measures analysis of variance, whereas ratings were evaluated using non-parametric Friedman analysis of variance. RESULTS: Oxygen uptake was higher in all three conditions with no or limited vision (Dark, Mono, and Bino) than in the Light condition (P ≤ 0.02) when walking on both the gravel road (+5-8%) and the forest trail (+6-14%). Heart rate was higher during the Dark than during the Light condition when walking on the forest trail, whereas there was no difference between conditions on the gravel road. During both trials, gait frequency was higher during the Dark than during the Light, Mono, and Bino conditions. Ratings were generally low during all conditions. CONCLUSIONS: Walking on a gravel road or a forest trail wearing a blindfold or visual aid increased the metabolic demand. Thus, it appears that the metabolic demand is higher during overground walking with night vision goggles than with full vision, which may influence the performance of nighttime operations.

Night Vision Anti-Halation Method Based on Infrared and Visible Video Fusion.

In order to address the discontinuity caused by the direct application of the infrared and visible image fusion anti-halation method to a video, an efficient night vision anti-halation method based on video fusion is proposed. The designed frame selection based on inter-frame difference determines the optimal cosine angle threshold by analyzing the relation of cosine angle threshold with nonlinear correlation information entropy and de-frame rate. The proposed time-mark-based adaptive motion compensation constructs the same number of interpolation frames as the redundant frames by taking the retained frame number as a time stamp. At the same time, considering the motion vector of two adjacent retained frames as the benchmark, the adaptive weights are constructed according to the interframe differences between the interpolated frame and the last retained frame, then the motion vector of the interpolated frame is estimated. The experimental results show that the proposed frame selection strategy ensures the maximum safe frame removal under the premise of continuous video content at different vehicle speeds in various halation scenes. The frame numbers and playing duration of the fused video are consistent with that of the original video, and the content of the interpolated frame is highly synchronized with that of the corresponding original frames. The average FPS of video fusion in this work is about six times that in the frame-by-frame fusion, which effectively improves the anti-halation processing efficiency of video fusion.

A randomized phase 2 clinical trial of phentolamine mesylate eye drops in patients with severe night vision disturbances.

PURPOSE: Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD. METHODS: In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed. RESULTS: Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia. CONCLUSION: PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD. TRIAL REGISTRATION: The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.

Comment on Richer et al. Night Vision and Carotenoids (NVC): A Randomized Placebo Controlled Clinical Trial on Effects of Carotenoid Supplementation on Night Vision in Older Adults. Nutrients 2021, 13, 3191.

Richer and colleagues [...].

Reply to Green-Gomez et al. Comment on "Richer et al. Night Vision and Carotenoids (NVC): A Randomized Placebo Controlled Clinical Trial on Effects of Carotenoid Supplementation on Night Vision in Older Adults. Nutrients 2021, 13, 3191".

We welcome the additional reviews and insights of Green-Gomez, Roche and Nolan [...].

Ancient whale rhodopsin reconstructs dim-light vision over a major evolutionary transition: Implications for ancestral diving behavior.

Cetaceans are fully aquatic mammals that descended from terrestrial ancestors, an iconic evolutionary transition characterized by adaptations for underwater foraging via breath-hold diving. Although the evolutionary history of this specialized behavior is challenging to reconstruct, coevolving sensory systems may offer valuable clues. The dim-light visual pigment, rhodopsin, which initiates phototransduction in the rod photoreceptors of the eye, has provided insight into the visual ecology of depth in several aquatic vertebrate lineages. Here, we use ancestral sequence reconstruction and protein resurrection experiments to quantify light-activation metrics in rhodopsin pigments from ancestors bracketing the cetacean terrestrial-to-aquatic transition. By comparing multiple reconstruction methods on a broadly sampled cetartiodactyl species tree, we generated highly robust ancestral sequence estimates. Our experimental results provide direct support for a blue-shift in spectral sensitivity along the branch separating cetaceans from terrestrial relatives. This blue-shift was 14 nm, resulting in a deep-sea signature (λmax = 486 nm) similar to many mesopelagic-dwelling fish. We also discovered that the decay rates of light-activated rhodopsin increased in ancestral cetaceans, which may indicate an accelerated dark adaptation response typical of deeper-diving mammals. Because slow decay rates are thought to help sequester cytotoxic photoproducts, this surprising result could reflect an ecological trade-off between rod photoprotection and dark adaptation. Taken together, these ancestral shifts in rhodopsin function suggest that some of the first fully aquatic cetaceans could dive into the mesopelagic zone (>200 m). Moreover, our reconstructions indicate that this behavior arose before the divergence of toothed and baleen whales.

Feasibility of Obtaining Intraosseous and Intravenous Access Using Night Vision Goggle Focusing Adaptors.

BACKGROUND: The optimal tactical lighting for performing medical procedures under low-light conditions is unclear. METHODS: United States Navy medical personnel (N = 23) performed intravenous (IV) and intraosseous (IO) procedures on mannequins using a tactical headlamp, night vision goggles (NVGs), and night vision goggles with focusing adaptors (NVG+A) utilizing a randomized within-subjects design. Procedure success, time to completion, and user preferences were analyzed using analysis of variance (ANOVA) and nonparametric statistics at p < .05. RESULTS: IV success rates were significantly greater for the headlamp (74%) than for NVG (35%; p < .03) and somewhat greater than for NVG+A (52%; p = .18). IO success rates were high under each lighting condition (96% to 100%). Time to completion was significantly faster using headlamp (IV, 106 ± 28 s; IO, 47 ± 11 s) than NVG (IV, 168 ± 80 s; IO, 56 ± 17 s) or NVG-A (IV, 157 ± 52 s; IO, 59 ± 27 s; each p < .01). Posttesting confidence on a 1-to-5 scale was somewhat higher for NVG+A (IV, 2.9 ± 0.2; IO, 4.2 ± 0.2) than for NVG (IV, 2.6 ± 0.2; IO, 4.0 ± 0.2). Participants cited concerns with NVG+A depth perception and with adjusting the adaptors, and that the adaptors were not integrated into the NVG. CONCLUSION: While this mannequin study was limited by laboratory conditions and by the lack of practice opportunities, we found some small advantages of focusing adaptors over NVG alone but not over headlamp for IV and IO access in low-light conditions.

Spatial Dissociation of Subretinal Drusenoid Deposits and Impaired Scotopic and Mesopic Sensitivity in AMD.

Purpose: Subretinal drusenoid deposits (SDD) first appear in the rod-rich perifovea and can extend to the cone-rich fovea. To refine the spatial relationship of visual dysfunction with SDD burden, we determined the topography of mesopic and scotopic light sensitivity in participants with non-neovascular AMD with and without SDD. Methods: Thirty-three subjects were classified into three groups: normal (n = 9), AMD-Drusen (with drusen and without SDD; n = 12), and AMD-SDD (predominantly SDD; n = 12). Mesopic and scotopic microperimetry were performed using 68 targets within the Early Treatment Diabetic Retinopathy Study grid, including points at 1.7° from the foveal center (rod:cone ratio, 0.35). Age-adjusted linear regression was used to compare mesopic and scotopic light sensitivities across groups. Results: Across the entire Early Treatment Diabetic Retinopathy Study grid and within individual subfields, the three groups differed significantly for mesopic and scotopic light sensitivities (all P < 0.05). The AMD-SDD group exhibited significantly decreased mesopic and scotopic sensitivity versus both the normal and the AMD-Drusen groups (all P < 0.05), while AMD-Drusen and normal eyes did not significantly differ (all P > 0.05). The lowest relative sensitivities were recorded for scotopic light levels, especially in the central subfield, in the AMD-SDD group. Conclusions: SDD-associated decrements in rod-mediated vision can be detected close to the foveola, and these deficits are proportionately worse than functional loss in the rod-rich perifovea. This finding suggests that factors other than the previously hypothesized direct cytotoxicity to photoreceptors and local transport barrier limitations may negatively impact vision. Larger prospective studies are required to confirm these observations.

Scotopic microperimetry: evolution, applications and future directions.

For many inherited and acquired retinal diseases, reduced night vision is a primary symptom. Despite this, the clinical testing options for spatially resolved scotopic vision have until recently been limited. Scotopic microperimetry is a relatively new visual function test that combines two-colour perimetry with fundus-controlled perimetry performed in scotopic luminance conditions. The technique enables spatially resolved mapping of central retinal sensitivity alongside the ability to distinguish between rod and cone photoreceptor sensitivities. Two companies produce commercially available scotopic microperimeters - Nidek (Nidek Technologies Srl, Padova, Italy) and CenterVue (CenterVue S.p.A., Padova, Italy). Scotopic microperimetry is a promising technology capable of detecting changes in retinal sensitivity before changes in other measures of visual function. Scotopic microperimetry is a promising functional biomarker that has the potential as a useful clinical trial outcome measure. This review summarises the evolution and applications of scotopic microperimetry, and discusses testing options, including testing grid selection, dark-adaptation time and threshold sensitivity analyses.

Influence of night vision goggles with white and green phosphor screens on selected parameters of the eye and fatigue.

In modern aviation, in particular in the military context, increasingly many aviation tasks are performed at night. To improve the safety of night flights, night vision goggles (NVGs) are commonly used. This study aimed to examine whether changes in ophthalmic parameters during NVGs use vary depending on phosphor screen type (green or white coded as P43 and P45 respectively). Thirteen participants were studied during a 2-h visual task in a night vision laboratory. Before and after NVGs use, we examined visual acuity, pachymetry, critical flicker-frequency thresholds, stereoscopic and contrast vision. During the use of NVGs, visual acuity, intra-ocular pressure and eye refraction were measured. We found no difference in visual performance between NVGs with green and white phosphor screens; however, NVGs use in general may lead to subjective eye fatigue, neck pain and headaches associated with the time of wearing and the weight of the helmet with additional equipment attached. Practitioner summary Night vision goggles (NVGs), widely used to improve the safety of night flights, were examined according to the applied type of the phosphor screen. There was no difference in visual performance between a white and green phosphor screens; however, NVGs and helmet manufacturers should strive to design these devices to be as lightweight as possible. Abbreviations: ANOVA: analysis of variance; CCT: central corneal thickness; CFF: critical flicker frequency; CNS: central nervous system; CS: contrast sensitivity; FOV: field-of-view; I2: image intensifier; IOP: intra-ocular pressure; NVGs: night vision goggles; SV: stereoscopic vision; VA: visual acuity; VAS: visual analog scale.

Effect of long-term chronic hyperhomocysteinemia on retinal structure and function in the cystathionine-ß-synthase mutant mouse.

Elevated levels of the excitatory amino acid homocysteine (Hcy) have been implicated in retinal diseases in humans including glaucoma and macular degeneration. It is not clear whether elevated Hcy levels are pathogenic. Models of hyperhomocysteinemia (Hhcy) have proven useful in addressing this including mice with deficiency in the enzyme cystathionine ß-synthase (CBS). Cbs+/- mice have a ∼two-fold increase in plasma and retinal Hcy levels. Previous studies of visual function and structure in Cbs+/- mice during the first 10 months of life revealed mild ganglion cell loss, but minimal electrophysiological alterations. It is not clear whether extended, chronic exposure to moderate Hhcy elevation will lead to visual function loss and retinal pathology. The present study addressed this by performing comprehensive analyses of retinal function/structure in 20 month Cbs+/- and Cbs+/+ (WT) mice including IOP, SD-OCT, scotopic and photopic ERG, pattern ERG (pERG), and visual acuity. Eyes were harvested for histology and immunohistochemical analysis of Brn3a (ganglion cells), dihydroethidium (oxidative stress) and GFAP (gliosis). The analyses revealed no difference in IOP between groups for age/strain. Visual acuity measured ∼0.36c/d for mice at 20 months in Cbs+/- and WT mice; contrast sensitivity did not differ between groups at either age. Similarly SD-OCT, scotopic/photopic ERG and pERG revealed no differences between 20 month Cbs+/- and WT mice. There was minimal disruption in retinal structure when eyes were examined histologically. Morphometric analysis revealed no significant differences in retinal layers. Immunohistochemistry revealed ∼5 RGCs/100 µm retinal length in both Cbs+/- and WT mice at 20 months. While there was greater oxidative stress and gliosis in older (20 month) mice versus young (4 month) mice, there was no difference in these parameters between the 20 month Cbs+/- and WT mice. We conclude that chronic, moderate Hhcy (at least due to deficiency of Cbs) is not accompanied by retinal structural/functional changes that differ significantly from age-matched WT littermates. Despite considerable evidence that severe Hhcy is toxic to retina, moderate Hhcy appears tolerated by retina suggesting compensatory cellular survival mechanisms.

Phototransduction in Anuran Green Rods: Origins of Extra-Sensitivity.

Green rods (GRs) represent a unique type of photoreceptor to be found in the retinas of anuran amphibians. These cells harbor a cone-specific blue-sensitive visual pigment but exhibit morphology of the outer segment typical for classic red rods (RRs), which makes them a perspective model object for studying cone-rod transmutation. In the present study, we performed detailed electrophysiological examination of the light sensitivity, response kinetics and parameters of discrete and continuous dark noise in GRs of the two anuran species: cane toad and marsh frog. Our results confirm that anuran GRs are highly specialized nocturnal vision receptors. Moreover, their rate of phototransduction quenching appeared to be about two-times slower than in RRs, which makes them even more efficient single photon detectors. The operating intensity ranges for two rod types widely overlap supposedly allowing amphibians to discriminate colors in the scotopic region. Unexpectedly for typical cone pigments but in line with some previous reports, the spontaneous isomerization rate of the GR visual pigment was found to be the same as for rhodopsin of RRs. Thus, our results expand the knowledge on anuran GRs and show that these are even more specialized single photon catchers than RRs, which allows us to assign them a status of "super-rods".

Conditional Deletion of Cytoplasmic Dynein Heavy Chain in Postnatal Photoreceptors.

Purpose: Cytoplasmic dynein-1 (henceforth dynein) moves cargo in conjunction with dynactin toward the minus end of microtubules. The dynein heavy chain, DYNC1H1, comprises the backbone of dynein, a retrograde motor. Deletion of Dync1h1 abrogates dynein function. The purpose of this communication is to demonstrate effects of photoreceptor dynein inactivation during late postnatal development and in adult retina. Methods: We mated Dync1h1F/F mice with iCre75 and Prom1-CreERT2 mice to generate conditional rod and tamoxifen-induced knockout in rods and cones, respectively. We documented retina degeneration with confocal microscopy at postnatal day (P) 10 to P30 for the iCre75 line and 1 to 4 weeks post tamoxifen induction (wPTI) for the Prom1-CreERT2 line. We performed scotopic and photopic electroretinography (ERG) at P16 to P30 in the iCre75 line and at 1-week increments in the Prom1-CreERT2 line. Results were evaluated statistically using Student's t-test, two-factor ANOVA, and Welch's ANOVA. Results: Cre-induced homologous recombination of Dync1h1F/F mice truncated DYNC1H1 after exon 23. rodDync1h1-/- photoreceptors degenerated after P14, reducing outer nuclear layer (ONL) thickness and combined inner segment/outer segment (IS/OS) length significantly by P18. Scotopic ERG a-wave amplitudes decreased by P16 and were extinguished at P30. Cones were stable under rod-knockout conditions until P21 but inactive at P30. In tamDync1h1-/- photoreceptors, the IS/OS began shortening by 3wPTI and were nearly eliminated by 4wPTI. The ONL shrank significantly over this interval, indicating rapid photoreceptor degeneration following the loss of dynein. Conclusions: Our results demonstrate dynein is essential for the secretory pathway, formation of outer segments, and photoreceptor maintenance.