Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 1.340
1.
Doc Ophthalmol ; 148(3): 133-143, 2024 Jun.
Article En | MEDLINE | ID: mdl-38451375

PURPOSE: Leber hereditary optic neuropathy (LHON) affects retinal ganglion cells causing severe vision loss. Pattern electroretinogram and photopic negative response (PhNR) of the light-adapted (LA) full-field electroretinogram (ERG) are typically affected in LHON. In the present study, we evaluated dark-adapted (DA) and LA oscillatory potentials (OPs) of the flash ERG in genetically characterized LHON patients to dissociate slow from fast components of the response. METHODS: Seven adult patients (mean age = 28.4 ± 5.6) in whom genetic diagnosis confirmed LHON with mtDNA or nuclear DNAJC30 (arLHON) pathogenic variants were compared to 12 healthy volunteers (mean age = 35.0 ± 12.1). Full-field ERGs were recorded from both eyes. Offline digital filters at 50, 75 and 100 Hz low cutoff frequencies were applied to isolate high-frequency components from the original ERG signals. RESULTS: ERG a-waves and b-waves were comparable between LHON patients and controls, while PhNR was significantly reduced (p = 0.009) in LHON patients compared to controls, as expected. OPs derived from DA signals (75 Hz low cutoff frequency) showed reduced peak amplitude for OP2 (p = 0.019). LA OP differences between LHON and controls became significant (OP2: p = 0.047, OP3: p = 0.039 and OP4: p = 0.013) when the 100 Hz low-cutoff frequency filter was applied. CONCLUSIONS: Reduced OPs in LHON patients may represent disturbed neuronal interactions in the inner retina with preserved photoreceptoral (a-wave) to bipolar cell (b-wave) activation. Reduced DA OP2 and high-cutoff LA OP alterations may be further explored as functional measures to characterize LHON status and progression.


Dark Adaptation , Electroretinography , Optic Atrophy, Hereditary, Leber , Photic Stimulation , Retinal Ganglion Cells , Humans , Electroretinography/methods , Optic Atrophy, Hereditary, Leber/physiopathology , Optic Atrophy, Hereditary, Leber/genetics , Optic Atrophy, Hereditary, Leber/diagnosis , Male , Adult , Female , Retinal Ganglion Cells/physiology , Young Adult , Dark Adaptation/physiology , Middle Aged , Visual Acuity/physiology
2.
Transl Vis Sci Technol ; 12(6): 13, 2023 Jun 01.
Article En | MEDLINE | ID: mdl-38752621

Purpose: Non-human primates (NHPs) are useful models for human retinal disease. Chromatic pupillometry has been proposed as a noninvasive method of identifying inherited retinal diseases (IRDs) in humans; however, standard protocols employ time-consuming dark adaptation. We utilized shortened and standard dark-adaptation protocols to compare pupillary light reflex characteristics following chromatic stimulation in rhesus macaques with achromatopsia to wild-type (WT) controls with normal retinal function. Methods: Nine rhesus macaques homozygous for the p.R656Q mutation (PDE6C HOMs) and nine WT controls were evaluated using chromatic pupillometry following 1-minute versus standard 20-minute dark adaptations. The following outcomes were measured and compared between groups: pupil constriction latency, peak constriction, pupil constriction time, and constriction velocity. Results: Pupil constriction latency was significantly longer in PDE6C HOMs with red-light (P = 0.0002) and blue-light (P = 0.04) stimulation versus WT controls. Peak constriction was significantly less in PDE6C HOMs with all light stimulation compared to WT controls (P < 0.0001). Pupil constriction time was significantly shorter in PDE6C HOMs versus WT controls with red-light (P = 0.04) and white-light (P = 0.003) stimulation. Pupil constriction velocity was significantly slower in PDE6C HOMs versus WT controls with red-light (P < 0.0001), blue-light (P < 0.0001), and white-light (P = 0.0002) stimulation. Dark adaptation time only significantly affected peak (P = 0.008) and time of pupil constriction (P = 0.02) following blue-light stimulation. Conclusions: Chromatic pupillometry following 1- and 20-minute dark adaptation is an effective tool for screening NHPs for achromatopsia. Translational Relevance: Rapid identification of NHPs with IRDs will provide animal research models to advance research and treatment of achromatopia in humans.


Color Vision Defects , Dark Adaptation , Disease Models, Animal , Macaca mulatta , Reflex, Pupillary , Animals , Reflex, Pupillary/physiology , Dark Adaptation/physiology , Color Vision Defects/genetics , Color Vision Defects/physiopathology , Color Vision Defects/diagnosis , Pupil/physiology , Cyclic Nucleotide Phosphodiesterases, Type 6/genetics , Male , Photic Stimulation , Female
3.
Retina ; 42(3): 569-575, 2022 03 01.
Article En | MEDLINE | ID: mdl-35188495

PURPOSE: To test the hypothesis that Müller cell dysfunction in macular telangiectasia type 2 (MacTel) results in delayed cone adaptation kinetics and to assess absolute cone and rod thresholds in this condition. METHODS: Adaptation after an approximate 63.5% full-field cone photopigment bleach was assessed for Goldmann size V (1.7° diameter) 640 nm (red) and 480 nm (blue) targets presented at a retinal locus corresponding to 2° temporal to fixation. The cone time constant of adaptation and absolute cone and rod thresholds were calculated from exponential functions fitted to the resultant dark adaptation curves. RESULTS: Eighteen eyes with MacTel (from 11 patients) were compared with 19 control eyes (from 16 normal subjects). Cone adaptation kinetics were significantly impaired in MacTel, as was the absolute cone threshold. Final thresholds for blue targets were also significantly elevated in MacTel, consistent with impaired rod absolute threshold. Losses in sensitivity observed in MacTel were consistent with a so-called d1/2 mechanism (i.e., receptoral) site of sensitivity loss. CONCLUSION: In addition to previously documented impairments in rod dark adaptation, MacTel results in a significant elevation in cone thresholds because of pathology at the level of the photoreceptors. The delays in cone adaptation that we found in eyes with MacTel may reflect impairment of the Müller cell-mediated cone-specific visual cycle.


Regeneration/physiology , Retinal Cone Photoreceptor Cells/physiology , Retinal Pigments/physiology , Retinal Telangiectasis/physiopathology , Aged , Aged, 80 and over , Cross-Sectional Studies , Dark Adaptation/physiology , Female , Humans , Male , Middle Aged , Prospective Studies , Visual Acuity/physiology , Visual Fields/physiology
4.
Sci Rep ; 12(1): 2475, 2022 02 15.
Article En | MEDLINE | ID: mdl-35169239

Delayed dark adaptation due to impaired rod photoreceptor homeostasis has been reported as the earliest symptom of eye diseases such as age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. Objective measurement of dark adaptation can facilitate early diagnosis to enable prompt intervention to prevent vision loss. However, there is a lack of noninvasive methods capable of spatiotemporal monitoring of photoreceptor changes during dark adaptation. Here we demonstrate functional optical coherence tomography (OCT) for in vivo intrinsic signal optoretinography (ORG) of dark adaptation kinetics in the C57BL/6J mouse retina. Functional OCT revealed a shortening of the outer retina, a rearrangement of the cone and rod photoreceptor interdigitation zone, and a reduction in intrinsic signal amplitude at the photoreceptor inner segment ellipsoid (ISe). A strong positive correlation between the outer retinal shortening and ISe intensity reduction was also confirmed. Functional OCT of dark adaptation kinetics promises an objective method for rapid ORG assessment of physiological integrity of retinal photoreceptors.


Blindness/diagnosis , Blindness/prevention & control , Dark Adaptation/physiology , Retinal Rod Photoreceptor Cells/physiology , Animals , Blindness/etiology , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Early Diagnosis , Kinetics , Macular Degeneration/complications , Macular Degeneration/diagnosis , Mice, Inbred C57BL , Retinitis Pigmentosa/complications , Retinitis Pigmentosa/diagnosis , Tomography, Optical Coherence/methods
5.
Plant Cell Physiol ; 63(1): 45-56, 2022 Jan 25.
Article En | MEDLINE | ID: mdl-34523687

Jasmonate (JA)-induced plant senescence has been mainly studied with a dark/starvation-promoted system using detached leaves; yet, the induction of whole-plant senescence by JA remains largely unclear. This work reports the finding of a JA-induced whole-plant senescence of tobacco under light/non-starvation conditions and the investigation of underlying regulations. Methyl jasmonate (MeJA) treatment induces the whole-plant senescence of tobacco in a light-intensity-dependent manner, which is suppressed by silencing of NtCOI1 that encodes the receptor protein of JA-Ile (the bioactive derivative of JA). MeJA treatment could induce the senescence-specific cysteine protease gene SAG12 and another cysteine protease gene SAG-L1 to high expression levels in the detached leaf patches under dark conditions but failed to induce their expression in tobacco whole plants under light conditions. Furthermore, MeJA attenuates the RuBisCo activase (RCA) level in the detached leaves but has no effect on this protein in the whole plant under light conditions. A genome-wide transcriptional assay also supports the presence of a differential regulatory pattern of senescence-related genes during MeJA-induced whole-plant senescence under non-starvation conditions and results in the finding of a chlorophylase activity increase in this process. We also observed that the MeJA-induced senescence of tobacco whole plants is reversible, which is accompanied by a structural change of chloroplasts. This work provides novel insights into JA-induced plant senescence under non-starvation conditions and is helpful to dissect the JA-synchronized process of whole-plant senescence.


Cyclopentanes/adverse effects , Nicotiana/genetics , Nicotiana/physiology , Oxylipins/adverse effects , Plant Senescence/drug effects , Plant Senescence/genetics , Adaptation, Ocular/genetics , Adaptation, Ocular/physiology , Dark Adaptation/genetics , Dark Adaptation/physiology , Gene Expression Regulation, Plant , Genes, Plant
6.
Plant Cell Physiol ; 63(1): 92-103, 2022 Jan 25.
Article En | MEDLINE | ID: mdl-34623443

Light-dependent activation of chloroplast enzymes is required for the rapid induction of photosynthesis after a shift from dark to light. The thioredoxin (Trx) system plays a central role in this process. In chloroplasts, the Trx system consists of two pathways: the ferredoxin (Fd)/Trx pathway and the nicotinamide adenine dinucleotide phosphate (NADPH)-Trx reductase C (NTRC) pathway. In Arabidopsis (Arabidopsis thaliana) mutants defective in either pathway, the photoreduction of thiol enzymes was impaired, resulting in decreased carbon fixation. The close relationship between the Fd/Trx pathway and proton gradient regulation 5 (PGR5)-dependent photosystem I cyclic electron transport (PSI CET) in the induction of photosynthesis was recently elucidated. However, how the PGR5-dependent pathway is involved in the NTRC pathway is unclear, although NTRC has been suggested to physically interact with PGR5. In this study, we analyzed Arabidopsis mutants lacking either the PGR5 or the chloroplast NADH dehydrogenase-like complex (NDH)-dependent PSI CET pathway in the ntrc mutant background. The ntrc pgr5 double mutant suppressed both the growth defects and the high non-photochemical quenching phenotype of the ntrc mutant when grown under long-day conditions. By contrast, the inactivation of NDH activity with the chlororespiratory reduction 2-2 mutant failed to suppress either phenotype. We discovered that the phenotypic rescue of ntrc by pgr5 is caused by the partial restoration of Trx-dependent reduction of thiol enzymes. These results suggest that electron partitioning to the PGR5-dependent pathway and the Trx system needs to be properly regulated for the activation of the Calvin-Benson-Bassham cycle enzymes during the induction of photosynthesis.


Arabidopsis/growth & development , Arabidopsis/genetics , Arabidopsis/metabolism , Chloroplasts/metabolism , Metabolic Networks and Pathways/radiation effects , Oxidation-Reduction/radiation effects , Thioredoxin-Disulfide Reductase/metabolism , Adaptation, Ocular/genetics , Adaptation, Ocular/physiology , Dark Adaptation/genetics , Dark Adaptation/physiology , Gene Expression Regulation, Plant , Genes, Plant , Genetic Variation , Genotype , Metabolic Networks and Pathways/genetics , Mutation , Photosynthesis/physiology , Thioredoxin-Disulfide Reductase/genetics
7.
Exp Eye Res ; 213: 108807, 2021 12.
Article En | MEDLINE | ID: mdl-34695438

The retinal circadian system consists of a network of clocks located virtually in every retinal cell-type. Although it is established that the circadian clock regulates many rhythmic processes in the retina, the links between retinal cell-specific clocks and visual function remain to be elucidated. Bmal1 is a principal, non-redundant component of the circadian clock in mammals and is required to keep 24 h rhythms in the retinal transcriptome and in visual processing under photopic light condition. In the current study, we investigated the retinal function in mice with a rod-specific knockout of Bmal1. For this purpose, we measured whole retina PER2::Luciferase bioluminescence and the dark-adapted electroretinogram (ERG). We observed circadian day-night differences in ERG a- and b-waves in control mice carrying one allele of Bmal1 in rods, with higher amplitudes during the subjective night. These differences were abolished in rod-specific Bmal1 knockout mice, whose ERG light-responses remained constitutively low (day-like). Overall, PER2::Luciferase rhythmicity in whole retinas was not defective in these mice but was characterized by longer period and higher rhythmic power compared to retinas with wild type Bmal1 gene. Taken together, these data suggest that a circadian clock located in rods regulates visual processing in a cell autonomous manner.


Circadian Clocks/physiology , Dark Adaptation/physiology , Retinal Rod Photoreceptor Cells/metabolism , ARNTL Transcription Factors/genetics , Animals , Electroretinography , Female , Gene Expression Regulation/physiology , Luciferases/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Night Vision/physiology , Period Circadian Proteins/metabolism , Photic Stimulation , Real-Time Polymerase Chain Reaction , Retinal Rod Photoreceptor Cells/radiation effects , Rhodopsin/genetics , Synaptophysin/genetics
8.
Invest Ophthalmol Vis Sci ; 62(13): 25, 2021 10 04.
Article En | MEDLINE | ID: mdl-34705026

Purpose: To provide a comprehensive analysis of light- and dark-adapted luminance thresholds and their associations with retinal structure in X-linked retinoschisis (XLRS). Methods: Nine subjects with XLRS and 10 visually-normal individuals participated. Threshold was measured at 15 locations along the horizontal meridian of the visual field at several adaptation levels (5 × 10-5 to 50 cd/m2) after dark-adaptation. The relationship between threshold and adaptation level across the field was described using a standard "threshold-versus-illuminance" model. Optical coherence tomography images were obtained and segmented to quantify outer nuclear layer (ONL+) and outer segment (OS+) thickness. A linear structure-function model was used to describe the relationship between threshold and the product of ONL+ and OS+ thickness. Results: For peripheral field measurements, thresholds were generally normal for most subjects with XLRS. All subjects had perifoveal and parafoveal threshold elevations under dark-adapted and high illuminance conditions, with thresholds at moderate illuminances being closer to normal. For foveal measurements, seven of nine subjects with XLRS had normal dark-adapted thresholds, and all had abnormally elevated high illuminance thresholds. Threshold-versus-illuminance curves in the fovea, parafovea, and perifovea were abnormally steep for subjects with XLRS, appearing similar to the normal peripheral field shape. Under both dark- and light-adapted conditions, threshold was predicted by ONL+ × OS+ thickness at nearly all field locations. Conclusions: Threshold elevation in XLRS is complex, depending on both the adaptation level and the visual field location. The pattern of threshold-versus-illuminance suggests that macular function in XLRS is similar to the periphery of controls.


Dark Adaptation/physiology , Fovea Centralis/diagnostic imaging , Retinoschisis/physiopathology , Tomography, Optical Coherence/methods , Visual Acuity , Visual Fields/physiology , Adolescent , Adult , Electroretinography , Female , Fovea Centralis/physiopathology , Humans , Male , Middle Aged , Photic Stimulation , Young Adult
9.
J Biol Chem ; 297(3): 101074, 2021 09.
Article En | MEDLINE | ID: mdl-34391781

Impaired dark adaptation (DA), a defect in the ability to adjust to dimly lit settings, is a universal hallmark of aging. However, the mechanisms responsible for impaired DA are poorly understood. Vitamin A byproducts, such as vitamin A dimers, are small molecules that form in the retina during the vitamin A cycle. We show that later in life, in the human eye, these byproducts reach levels commensurate with those of vitamin A. In mice, selectively inhibiting the formation of these byproducts, with the investigational drug C20D3-vitamin A, results in faster DA. In contrast, acutely increasing these ocular byproducts through exogenous delivery leads to slower DA, with otherwise preserved retinal function and morphology. Our findings reveal that vitamin A cycle byproducts alone are sufficient to cause delays in DA and suggest that they may contribute to universal age-related DA impairment. Our data further indicate that the age-related decline in DA may be tractable to pharmacological intervention by C20D3-vitamin A.


Dark Adaptation/physiology , Retina/metabolism , Vitamin A/metabolism , Aging , Animals , Dark Adaptation/genetics , Eye/drug effects , Eye/metabolism , Humans , Macular Degeneration/physiopathology , Male , Mice , Mice, Inbred ICR , Retina/drug effects , Retinal Degeneration/physiopathology , Retinal Pigment Epithelium/drug effects , Retinal Pigment Epithelium/metabolism , Visual Acuity/drug effects , Visual Acuity/physiology , Vitamin A/antagonists & inhibitors , Vitamin A/physiology
10.
Photosynth Res ; 148(3): 137-152, 2021 Jun.
Article En | MEDLINE | ID: mdl-34236566

The heliobacteria, a family of anoxygenic phototrophs, possess the simplest known photosynthetic apparatus. Although they are photoheterotrophs in the light, the heliobacteria can also grow chemotrophically via pyruvate metabolism in the dark. In the heliobacteria, the cytochrome bc complex is responsible for oxidizing menaquinol and reducing cytochrome c553 in the electron flow cycle used for phototrophy. However, there is no known electron acceptor for the mobile cytochrome c553 other than the photochemical reaction center. We have, therefore, hypothesized that the cytochrome bc complex is necessary for phototrophy, but unnecessary for chemotrophic growth in the dark. We used a two-step method for CRISPR-based genome editing in Heliobacterium modesticaldum to delete the genes encoding the four major subunits of the cytochrome bc complex. Genotypic analysis verified the deletion of the petCBDA gene cluster encoding the catalytic components of the complex. Spectroscopic studies revealed that re-reduction of cytochrome c553 after flash-induced photo-oxidation was over 100 times slower in the ∆petCBDA mutant compared to the wild-type. Steady-state levels of oxidized P800 (the primary donor of the photochemical reaction center) were much higher in the ∆petCBDA mutant at every light level, consistent with a limitation in electron flow to the reaction center. The ∆petCBDA mutant was unable to grow phototrophically on acetate plus CO2 but could grow chemotrophically on pyruvate as a carbon source similar to the wild-type strain in the dark. The mutants could be complemented by reintroduction of the petCBDA gene cluster on a plasmid expressed from the clostridial eno promoter.


Cell Survival/physiology , Clostridiales/genetics , Clostridiales/metabolism , Cytochromes/genetics , Cytochromes/metabolism , Gene Deletion , Photosynthesis/physiology , Adaptation, Ocular/genetics , Adaptation, Ocular/physiology , Dark Adaptation/genetics , Dark Adaptation/physiology , Mutation , Photosynthesis/genetics
11.
Exp Eye Res ; 209: 108698, 2021 08.
Article En | MEDLINE | ID: mdl-34228964

Vision requires the transport and recycling of the pigment 11-cis retinaldehyde (retinal) between the retinal pigment epithelium (RPE) and photoreceptors. 11-cis retinal is also required for light-mediated photoreceptor death in dark-adapted mouse eye, probably through overstimulation of rod cells adapted for low light. Retbindin is a photoreceptor-specific protein, of unclear function, that is localized between the RPE and the tips of the photoreceptors. Unexpectedly, young Rtbdn-KO mice, with targeted deletion (KO) of retbindin, showed delayed regeneration of retinal function after bleaching and were strongly resistant to light-induced photoreceptor death. Furthermore, bio-layer interferometry binding studies showed recombinant retbindin had significant affinity for retinoids, most notably 11-cis retinal. This suggests that retbindin mediates light damage, probably through a role in transport of 11-cis retinal. In Rtbdn-KO mice, retinal development was normal, as were amplitudes of rod and cone electroretinograms (ERG) up to 4 months, although implicit times and c-waves were affected. However, with aging, both light- and dark-adapted ERG amplitudes declined significantly and photoreceptor outer segments became disordered, However, in contrast to other reports, there was little retinal degeneration or drop in flavin levels. The RPE developed vacuoles and lipid, protein and calcium deposits reminiscent of age-related macular degeneration. Other signs of premature aging included loss of OPN4+ retinal ganglion cells and activation of microglia. Thus, retbindin plays an unexpected role in the mammalian visual cycle, probably as an adaptation for vision in dim light. It mediates light damage in the dark-adapted eye, but also plays a role in light-adapted responses and in long term retinal homeostasis.


Aging, Premature/genetics , Eye Proteins/genetics , Gene Expression Regulation , RNA/genetics , Retinal Cone Photoreceptor Cells/metabolism , Retinal Diseases/genetics , Retinal Pigment Epithelium/metabolism , Aging, Premature/metabolism , Animals , Dark Adaptation/physiology , Disease Models, Animal , Electroretinography , Eye Proteins/biosynthesis , Mice , Microscopy, Electron, Transmission , Retinal Cone Photoreceptor Cells/ultrastructure , Retinal Diseases/metabolism , Retinal Diseases/pathology , Retinal Pigment Epithelium/ultrastructure
12.
Sci Rep ; 11(1): 10349, 2021 05 14.
Article En | MEDLINE | ID: mdl-33990634

To evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75-0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.


Aging/physiology , Dark Adaptation/physiology , Macular Degeneration/physiopathology , Retinal Drusen/physiopathology , Retinal Rod Photoreceptor Cells/physiology , Adult , Healthy Volunteers , Humans , Macular Degeneration/diagnosis , Male , Middle Aged , Reproducibility of Results , Retinal Drusen/diagnosis , Visual Field Tests/methods , Visual Field Tests/statistics & numerical data
13.
Invest Ophthalmol Vis Sci ; 62(4): 29, 2021 04 01.
Article En | MEDLINE | ID: mdl-33891680

Purpose: The purpose of this study was to characterize changes in the full-field flash electroretinogram (ERG) in association with psychophysical dark-adapted visual thresholds in patients with genetically characterized Duchenne muscular dystrophy (DMD) either lacking Dp427 (Up 30) or at least Dp260 in addition to Dp427 (Down 30). Methods: Twenty-one patients with DMD and 27 age-similar controls participated in this study. Dark-adapted (0.01, 3.0, and 10 cd.s/m² flashes) and light-adapted (3.0 cd.s/m² flash) ERGs were recorded following International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. Visual detection thresholds to 625-nm (cone function) and 527-nm (rod function) light-emitting diode (LED) flashes (2 degree diameter) were measured during a dark adaptation period after a 1-minute exposure to a bleaching light (3000 cd/m²). Initially, 8 minutes of interleaved 625-nm and 527-nm thresholds were measured. After an additional 5 minutes of dark-adaptation, a second set of threshold measurements to 527-nm stimuli was performed during the subsequent 6 minutes. Results: Dark-adapted b-wave amplitude was significantly reduced to all strengths of flash and a-wave in response to the strong flash stimulus was delayed (15.6 vs. 14.7 ms, P < 0.05) in patients with Down 30 compared with controls. Dark-adapted cone thresholds did not differ among the groups (-2.0, -1.8, and -1.7 log cd/m² for Down 30, Up 30, and controls, respectively, P = 0.21). In contrast, dark-adapted rod thresholds were elevated (F(2,36) = 8.537, P = 0.001) in patients with Down 30 (mean = -3.2 ± 1.1 log cd/m²) relative to controls (mean = -4.2 ± 0.3 log cd/m²). Dark-adapted b-wave amplitudes were correlated with dark-adapted rod sensitivity in patients with DMD (Spearman Rho = 0.943, P = 0.005). The changes were much smaller or absent in patients with intact Dp260. Conclusions: Dp260 is particularly required for normal rod-system function in dark adaptation.


Dark Adaptation/physiology , Electroretinography/methods , Muscular Dystrophy, Duchenne/physiopathology , Retinal Cone Photoreceptor Cells/metabolism , Sensory Thresholds/physiology , Visual Perception/physiology , Adolescent , Child , Female , Humans , Male , Muscular Dystrophy, Duchenne/pathology , Photic Stimulation , Retinal Cone Photoreceptor Cells/pathology , Young Adult
14.
Mol Vis ; 27: 78-94, 2021.
Article En | MEDLINE | ID: mdl-33688152

Purpose: To describe clinical and genetic features in a series of Italian patients with sector retinitis pigmentosa (sector RP). Methods: Fifteen patients with sector RP were selected from the database of Hereditary Retinal Degenerations Referring Center of Careggi Hospital (Florence, Italy). Eleven patients from five independent pedigrees underwent genetic analysis with next-generation sequencing (NGS) confirmed with Sanger sequencing. The diagnosis of sector RP was based on the detection of topographically limited retinal abnormalities consistent with corresponding sectorial visual field defects. Best-corrected visual acuity (BCVA), fundus color pictures as well as fundus autofluorescence (FAF), spectral domain-optical coherence tomography (SD-OCT), full-field electroretinography (ERG), and 30-2 Humphrey visual field (VF) data were retrospectively collected and analyzed. Results: For the 30 eyes, the mean BCVA was 0.05 ± 0.13 logMAR, and the mean refractive error was -0.52 ± 1.89 D. The inferior retina was the most affected sector (86.7%), and the VF defect corresponded to the affected sector. FAF showed a demarcation line of increased autofluorescence between the healthy and affected retina, corresponding on SD-OCT to an interruption of the ellipsoid zone (EZ) band in the diseased retina. Dark-adapted ERG amplitudes were decreased in comparison to normative values. In five unrelated families, the sector RP phenotype was associated with sequence variants in the RHO gene. The same mutation c.568G>A p.(Asp190Asn) was found in nine patients of four families. Conclusions: Typical sector RP is a mild form of RP characterized by preserved visual acuity with limited retinal involvement and, generally, a more favorable prognosis than other forms of RP.


Retinitis Pigmentosa/diagnosis , Retinitis Pigmentosa/genetics , Rhodopsin/genetics , Adult , Aged , Dark Adaptation/physiology , Electroretinography , Female , High-Throughput Nucleotide Sequencing , Humans , Italy/epidemiology , Male , Middle Aged , Pedigree , Phenotype , Refraction, Ocular/physiology , Retina/physiopathology , Retinitis Pigmentosa/physiopathology , Retrospective Studies , Tomography, Optical Coherence , Visual Acuity/physiology , Visual Field Tests , Visual Fields/physiology , Young Adult
15.
Ophthalmic Genet ; 42(3): 296-299, 2021 06.
Article En | MEDLINE | ID: mdl-33691579

The complete form of congenital stationary night blindness (cCSNB) represents a non-progressive retinal disorder characterized by night vision problems and often congenital nystagmus, reduced vision, high myopia, strabismus and normal fundus appearance. Clinically this form of CSNB can be diagnosed by full-field electroretinogram. The mode of inheritance can be X-linked and autosomal recessive with mutations in genes coding for proteins mainly present at the dendritic tips of ON-bipolar cells. Mutations in NYX, GRM6, GPR179, LRIT3 and TRPM1 lead to this condition. The latter gene defect represents the major form underlying cCSNBC. It codes for the melastatin-related transient receptor 1 expressed in the inner nuclear layer of the retina, with the protein localized in ON-bipolar cells. To date, various homozygous or compound heterozygous mutations in TRPM1 have been reported. Small chromosomal rearrangements are frequent cause of mental retardation. In rare cases deletions can overlap with a mutation on the remaining chromosome and lead to a recessive disorder. Here, we describe a patient with mild neurological deficiencies and cCSNB caused by a microdeletion on 15q32 overlapping with a TRPM1 variant.


Eye Diseases, Hereditary/genetics , Genetic Diseases, X-Linked/genetics , Learning Disabilities/genetics , Mutation, Missense/genetics , Myopia/genetics , Night Blindness/genetics , TRPM Cation Channels/genetics , Child, Preschool , Chromosome Deletion , Chromosomes, Human, Pair 15/genetics , Dark Adaptation/physiology , Electroretinography , Eye Diseases, Hereditary/diagnosis , Female , Genetic Diseases, X-Linked/diagnosis , Genotype , Heterozygote , Humans , Learning Disabilities/diagnosis , Myopia/diagnosis , Night Blindness/diagnosis , Photic Stimulation
16.
Plant Sci ; 305: 110828, 2021 Apr.
Article En | MEDLINE | ID: mdl-33691962

The water-water cycle (WWC) has the potential to alleviate photoinhibition of photosystem I (PSI) in fluctuating light (FL) at room temperature and moderate heat stress. However, it is unclear whether WWC can function as a safety valve for PSI in FL at chilling temperature. In this study, we measured P700 redox state and chlorophyll fluorescence in FL at 25 °C and 4 °C in the high WWC activity plant Dendrobium officinale. At 25 °C, the operation of WWC contributed to the rapid re-oxidation of P700 upon dark-to-light transition. However, such rapid re-oxidation of P700 was not observed at 4 °C. Upon a sudden increase in light intensity, WWC rapidly consumed excess electrons in PSI and thus avoided an over-reduction of PSI at 25 °C. On the contrary, PSI was highly reduced within the first seconds after transition from low to high light at 4 °C. Therefore, in opposite to 25 °C, the WWC is not a major alternative sink in FL at chilling temperature. Upon transition from low to high light, cyclic electron transport was highly stimulated at 4 °C when compared with 25 °C. These results indicate that D. officinale enhances cyclic electron transport to partially compensate for the inactivation of WWC in FL at 4 °C.


Adaptation, Ocular/physiology , Cold Temperature , Dark Adaptation/physiology , Dendrobium/physiology , Electron Transport/physiology , Heat-Shock Response/physiology , Photosystem I Protein Complex/physiology , Photosynthesis/physiology , Plant Leaves/physiology
17.
Retina ; 41(10): 2098-2105, 2021 Oct 01.
Article En | MEDLINE | ID: mdl-33625114

PURPOSE: To assess the relationship between baseline age-related macular degeneration (AMD) and disease stage, as well as optical coherence tomography features seen in AMD, with 3-year changes in dark adaptation (DA). METHODS: Prospective longitudinal study including patients with AMD and a comparison group (n = 42 eyes, 27 patients). At baseline and 3 years, we obtained color fundus photographs, spectral-domain optical coherence tomography, and rod-mediated DA (20 minutes protocol). Multilevel mixed-effect models were used for analyses, with changes in rod intercept time at 3 years as the primary outcome. As some eyes (n = 11) reached the DA testing ceiling value at baseline, we used 3-year changes in area under the DA curve as an additional outcome. RESULTS: Baseline AMD, AMD stage, and hyperreflective foci on optical coherence tomography were associated with larger changes in rod intercept time at 3 years. When change in area under the DA curve was used as an outcome, in addition to these features, the presence of retinal atrophy and drusenoid pigment epithelial detachment had significant associations. New subretinal drusenoid deposits at 3 years were also associated with more pronounced changes in rod intercept time and area under the DA curve. CONCLUSION: Specific optical coherence tomography features are associated with DA impairments over time, which supports that structural changes predict functional loss over 3 years.


Dark Adaptation/physiology , Macular Degeneration/physiopathology , Retinal Rod Photoreceptor Cells/physiology , Aged , Area Under Curve , Female , Follow-Up Studies , Humans , Macular Degeneration/diagnostic imaging , Male , Middle Aged , Prospective Studies , Retinal Drusen/physiopathology , Tomography, Optical Coherence , Visual Acuity/physiology
18.
Plant Physiol ; 185(1): 228-239, 2021 02 25.
Article En | MEDLINE | ID: mdl-33631808

Optimal plant growth performance requires that the presence and action of growth signals, such as gibberellins (GAs), are coordinated with the availability of photo-assimilates. Here, we studied the links between GA biosynthesis and carbon availability, and the subsequent effects on growth. We established that carbon availability, light and dark cues, and the circadian clock ensure the timing and magnitude of GA biosynthesis and that disruption of these factors results in reduced GA levels and expression of downstream genes. Carbon-dependent nighttime induction of gibberellin 3-beta-dioxygenase 1 (GA3ox1) was severely hampered when preceded by reduced daytime light availability, leading specifically to reduced bioactive GA4 levels, and coinciding with a decline in leaf expansion rate during the night. We attributed this decline in leaf expansion mostly to reduced photo-assimilates. However, plants in which GA limitation was alleviated had significantly improved leaf expansion, demonstrating the relevance of GAs in growth control under varying carbon availability. Carbon-dependent expression of upstream GA biosynthesis genes (Kaurene synthase and gibberellin 20 oxidase 1, GA20ox1) was not translated into metabolite changes within this short timeframe. We propose a model in which the extent of nighttime biosynthesis of bioactive GA4 by GA3ox1 is determined by nighttime consumption of starch reserves, thus providing day-to-day adjustments of GA responses.


Arabidopsis/growth & development , Arabidopsis/metabolism , Carbon/metabolism , Circadian Clocks/physiology , Gibberellins/metabolism , Photosynthesis/physiology , Plant Leaves/growth & development , Plant Leaves/metabolism , Adaptation, Ocular/physiology , Dark Adaptation/physiology , Genetic Variation , Genotype , Plant Development/drug effects
19.
Acta Ophthalmol ; 99(7): 765-772, 2021 Nov.
Article En | MEDLINE | ID: mdl-33393736

PURPOSE: Numerous small hyperreflective dots (HRDs) can be seen within the hyporeflective layer between the ellipsoid zone (EZ) and the interdigitation zone (IZ) on C-scan spectral-domain optical coherence tomography (SD-OCT) with a yet unknown variation under light conditions. The aim of this study was to explore light-induced SD-OCT changes in these HRDs. METHODS: The study subjects were randomly assigned to two groups: Group 1 experienced a dark adaptation protocol followed by intense retinal photobleaching, while Group 2, serving as the control group, was exposed to constant ambient light without any variation. The number of HRDs was automatically counted. RESULTS: Twenty healthy volunteers were prospectively included. The number of HRDs differed significantly over time (p = 0.0013). They decreased in Group 1 after dark adaptation and retinal photobleaching before returning to baseline levels 30 min later; conversely, they remained relatively constant in Group 2 throughout the study (p < 0.001). Light-skinned subjects had less HRD than dark-skinned subjects. CONCLUSION: We observed light-induced modifications in the space between the EZ and the IZ. We hypothesize that the HRDs visible in this zone correspond to melanosomes that are mobilized during the light stimulation protocol. Larger studies are recommended to further evaluate and confirm light-induced SD-OCT changes under physiological and pathological conditions.


Dark Adaptation/physiology , Light , Retinal Photoreceptor Cell Outer Segment/radiation effects , Retinal Pigment Epithelium/diagnostic imaging , Tomography, Optical Coherence/methods , Adult , Female , Follow-Up Studies , Healthy Volunteers , Humans , Male , Prospective Studies , Retinal Photoreceptor Cell Outer Segment/physiology , Retinal Pigment Epithelium/physiology , Visual Acuity
20.
Ophthalmic Physiol Opt ; 41(2): 213-223, 2021 03.
Article En | MEDLINE | ID: mdl-33403668

PURPOSE: The measurement of standard visual acuity (VA) is the most well-known part of any ophthalmic examination to indicate visual function. Despite this, it is insensitive in detecting early disease changes. Therefore, other visual function tests have been developed including low luminance VA (LLVA) and low luminance deficit (LLD). This scoping literature review aims to summarise the current published applications of LLVA and LLD assessments to evaluate their utility as clinical markers and research outcome measures in a variety of ophthalmic conditions. RECENT FINDINGS: Sixty-five peer-reviewed publications were included. LLVA was pioneered for use in geographic atrophy, a subtype of age-related macular degeneration, which remains the mainstay of its clinical application. However, other studies have reported additional useful applications in inherited retinal diseases including rare maculopathies and rod-cone dystrophies. Although there are some variations in testing methodology, use of the standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart with a 2.0 log unit neutral density filter is the most popular approach. The optimal testing luminance is still to be defined. SUMMARY: Overall, LLVA is an earlier clinical marker of change in central retinal function than standard VA. It has been shown to be a risk factor for disease progression and a better indicator of a patient's level of everyday visual function. It is inexpensive and simple to implement using readily available standard ophthalmic equipment.


Dark Adaptation/physiology , Lighting/methods , Macular Degeneration/physiopathology , Night Vision/physiology , Retina/physiopathology , Visual Acuity , Visual Fields/physiology , Humans , Vision Tests
...