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American Journal of Ophthalmology Jul 2024To evaluate ocular and retinal features of CRB1-associated early onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) for age-related changes.
PURPOSE
To evaluate ocular and retinal features of CRB1-associated early onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) for age-related changes.
DESIGN
Retrospective cohort study.
METHODS
Sixteen pediatric patients with biallelic CRB1 EOSRD/LCA who had been followed for up to 18 years were reviewed. Results of comprehensive ophthalmic examinations-including visual acuity, refractive error, dark-adapted visual threshold, Goldmann perimetry, and macular optical coherence tomography (OCT)-were analyzed for significant age-related changes using mixed-effects models.
RESULTS
Visual acuity dark-adapted visual sensitivity, and area of seeing visual field (all subnormal from the earliest ages recorded) declined with increasing age. Hyperopia was stable through childhood and adolescence. In CRB1 EOSRD/LCA, OCT extrafoveal inner and outer laminar thicknesses exceeded those in controls but varied little with age, and foveal metrics (depth, breadth, thickness at rim) differed significantly from those in controls, but variations in foveal metrics were not associated with declines in acuity.
CONCLUSIONS
From the youngest ages, retinal and visual function is significantly subnormal and becomes progressively compromized. A goal of future therapies should be intervention at young ages, when there is more function to be rescued.
Topics: Humans; Child; Retrospective Studies; Visual Acuity; Tomography, Optical Coherence; Male; Adolescent; Female; Child, Preschool; Eye Proteins; Nerve Tissue Proteins; Membrane Proteins; Visual Fields; Leber Congenital Amaurosis; Visual Field Tests; Retinal Dystrophies; Dark Adaptation; Infant; Aging; Follow-Up Studies; Retina; Young Adult
PubMed: 38461945
DOI: 10.1016/j.ajo.2024.02.028 -
BMC Biology Dec 2023Rhabdomeric photoreceptors of eyes in the terrestrial slug Limax are the typical invertebrate-type but unique in that three visual opsins (Gq-coupled rhodopsin,...
BACKGROUND
Rhabdomeric photoreceptors of eyes in the terrestrial slug Limax are the typical invertebrate-type but unique in that three visual opsins (Gq-coupled rhodopsin, xenopsin, Opn5A) and one retinochrome, all belonging to different groups, are co-expressed. However, molecular properties including spectral sensitivity and G protein selectivity of any of them are not determined, which prevents us from understanding an advantage of multiplicity of opsin properties in a single rhabdomeric photoreceptor. To gain insight into the functional role of the co-expression of multiple opsin species in a photoreceptor, we investigated the molecular properties of the visual opsins in the present study.
RESULTS
First, we found that the fourth member of visual opsins, Opn5B, is also co-expressed in the rhabdomere of the photoreceptor together with previously identified three opsins. The photoreceptors were also demonstrated to express Gq and Go alpha subunits. We then determined the spectral sensitivity of the four visual opsins using biochemical and spectroscopic methods. Gq-coupled rhodopsin and xenopsin exhibit maximum sensitivity at ~ 456 and 475 nm, respectively, and Opn5A and Opn5B exhibit maximum sensitivity at ~ 500 and 470 nm, respectively, with significant UV sensitivity. Notably, in vitro experiments revealed that Go alpha was activated by all four visual opsins, in contrast to the specific activation of Gq alpha by Gq-coupled rhodopsin, suggesting that the eye photoreceptor of Limax uses complex G protein signaling pathways.
CONCLUSIONS
The eye photoreceptor in Limax expresses as many as four different visual opsin species belonging to three distinct classes. The combination of opsins with different spectral sensitivities and G protein selectivities may underlie physiological properties of the ocular photoreception, such as a shift in spectral sensitivity between dark- and light-adapted states. This may be allowed by adjustment of the relative contribution of the four opsins without neural networks, enabling a simple strategy for fine-tuning of vision.
Topics: Animals; Opsins; Photoreceptor Cells, Invertebrate; Rhodopsin; Mollusca; GTP-Binding Proteins
PubMed: 38110917
DOI: 10.1186/s12915-023-01789-7 -
Investigative Ophthalmology & Visual... Sep 2023To describe a group of patients with retinitis pigmentosa GTPase regulator (RPGR)-related retinopathy with a tapetal-like retinal sheen and corresponding changes in the...
PURPOSE
To describe a group of patients with retinitis pigmentosa GTPase regulator (RPGR)-related retinopathy with a tapetal-like retinal sheen and corresponding changes in the reflectivity of the ellipsoid zone on optical coherence tomography (OCT) imaging.
METHODS
A retrospective case series of 66 patients with a disease-causing variant in RPGR was performed. An expert examiner, masked to patient demographics, clinical evaluations, and specific RPGR variant, analyzed color fundus photographs for the presence of a tapetal-like retinal sheen and assessed OCT images for the presence of an abnormally broad hyper-reflective band in the outer retina. Longitudinal reflectivity profiles were generated and compared with healthy controls.
RESULTS
Twelve patients (18.2%) had a retinal sheen on color images that cosegregated with an abnormally broad hyper-reflective ellipsoid zone band on OCT imaging. Three-fourths of these patients were male, had a cone-rod dystrophy, and had pathogenic RPGR variants located toward the 3'-end of ORF15. This group had a different longitudinal reflectivity profile signature compared with controls. After a period of prolonged dark adaptation, the abnormal hyper-reflective band on OCT became less apparent, and the outer retinal layers adopted a more normal appearance.
CONCLUSIONS
RPGR-related retinopathy should be considered for males presenting with retinal sheen, abnormal ellipsoid zone hyper-reflectivity, and cone or cone-rod dysfunction on ERG, and pursued with molecular testing. Our results have implications for understanding the role of the C-terminal domain encoded by RPGR ORF15 in the phototransduction cascade. Further, the findings may be important to incorporate into both inclusion criteria and outcome measure developments in future RPGR-related cone or cone-rod dystrophy clinical trials.
Topics: Humans; Male; Female; Cone-Rod Dystrophies; Retrospective Studies; Retina; Retinal Cone Photoreceptor Cells; Retinal Diseases; Eye Proteins
PubMed: 37695603
DOI: 10.1167/iovs.64.12.19 -
Documenta Ophthalmologica. Advances in... Jun 2024Leber hereditary optic neuropathy (LHON) affects retinal ganglion cells causing severe vision loss. Pattern electroretinogram and photopic negative response (PhNR) of...
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.
Topics: Humans; Electroretinography; Optic Atrophy, Hereditary, Leber; Male; Adult; Female; Retinal Ganglion Cells; Photic Stimulation; Young Adult; Dark Adaptation; Middle Aged; Visual Acuity
PubMed: 38451375
DOI: 10.1007/s10633-024-09968-9 -
Photochemical & Photobiological... Aug 2023A putative xanthorhodopsin-encoding gene, XR34, was found in the genome of the moderately halophilic gammaproteobacterium Salinivibrio socompensis S34, isolated from...
A putative xanthorhodopsin-encoding gene, XR34, was found in the genome of the moderately halophilic gammaproteobacterium Salinivibrio socompensis S34, isolated from modern stromatolites found on the shore of Laguna Socompa (3570 m), Argentina Puna. XR-encoding genes were clustered together with genes encoding X-carotene, retinal (vitamin-A aldehyde), and carotenoid biosynthesis enzymes while the carotene ketolase gene critical for the salinixanthin antenna compound was absent. To identify its functional behavior, we herein overexpressed and characterized this intriguing microbial rhodopsin. Recombinant XR34 showed all the salient features of canonical microbial rhodopsin and covalently bound retinal as a functional chromophore with λ = 561 nm (ε ca. 60,000 M cm). Two canonical counterions with pK values of around 6 and 3 were identified by pH titration of the recombinant protein. With a recovery time of approximately half an hour in the dark, XR34 shows light-dark adaptation shifting the absorption maximum from 551 to 561 nm. Laser-flash induced photochemistry at pH 9 (deprotonated primary counterion) identified a photocycle starting with a K-like intermediate, followed by an M-state (λ ca. 400 nm, deprotonated Schiff base), and a final long wavelength-absorbing N- or O-like intermediate before returning to the parental 561 nm-state. Initiating the photocycle at pH 5 (protonated counterion) yields only bathochromic intermediates, due to the lacking capacity of the counterion to accept the Schiff base proton. Illumination of the membrane-embedded protein yielded a capacitive transport current. The presence of the M-intermediate under these conditions was demonstrated by a blue light-induced shunt process.
Topics: Schiff Bases; Carotenoids; Retinaldehyde; Rhodopsins, Microbial; Hydrogen-Ion Concentration; Bacteriorhodopsins
PubMed: 37036621
DOI: 10.1007/s43630-023-00412-6 -
Ophthalmology Science Sep 2023
Re: Higgins et al.: Assessment of the classification of age-related macular degeneration severity from the Northern Ireland Sensory Ageing Study using a measure of dark adaptation ( 2023;3(2):100204).
PubMed: 37692378
DOI: 10.1016/j.xops.2023.100376 -
BMC Veterinary Research Aug 2023In modern times, horses are utilized not only for labour and transportation purposes but also for recreational activities such as competition and pleasure riding. In...
BACKGROUND
In modern times, horses are utilized not only for labour and transportation purposes but also for recreational activities such as competition and pleasure riding. In these various pursuits, the role of vision plays a crucial role. Electroretinography is the most used test to diagnose diseases of the retinal outer segment. There is a wide variety of devices to perform the electroretinography differing one from each other in the corneal electrode and the light stimulation. The Koijman electrode has been tested in dogs but not in horses. The main purpose of this study was to compare electroretinography parameters from horses sedated with detomidine alone or in combination with butorphanol, during a standardized protocol using the Koijman electrode and RETI-port® system. Seven mares were allocated to the detomidine and detomidine plus butorphanol group in a randomised, controlled, crossover study. Friedman and Willcoxon-signed ranked tests were used to compare the electroretinogram parameters. A Student's t-test was used to compare differences in the number of artefacts to valid values ratio obtained under both sedation protocols.
RESULTS
Dark adaptation peaked after 16 min under scotopic conditions in both groups. No significant differences in electroretinogram parameters between groups were observed. During the mixed rod and cone response evaluation under scotopic conditions, all mares made a movement of the head resulting in a high number of artefacts. The detomidine plus butorphanol group showed a non-significant tendency to have fewer artefacts and a longer duration of sedation compared to the detomidine group.
CONCLUSIONS
Detomidine alone or combined with butorphanol may be suitable to use Koijman electrode and the RETI-port® to perform a standardized long protocol in horses with some adaptations.
Topics: Horses; Animals; Female; Dogs; Butorphanol; Electroretinography; Hypnotics and Sedatives; Cross-Over Studies; Imidazoles; Electrodes; Clinical Trials, Veterinary as Topic
PubMed: 37537621
DOI: 10.1186/s12917-023-03654-9 -
Cell Reports May 2024Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment...
Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment epithelium (RPE) and Müller glia (MG), but the relative functional importance of these two cellular pools is debated. Here, we report RPE- and MG-specific CRALBP knockout (KO) mice and examine their photoreceptor and visual cycle function. Bulk visual chromophore regeneration in RPE-KO mice is 15-fold slower than in controls, accounting for their delayed rod dark adaptation and protection against retinal phototoxicity, whereas MG-KO mice have normal bulk visual chromophore regeneration and retinal light damage susceptibility. Cone pigment regeneration is significantly impaired in RPE-KO mice but mildly affected in MG-KO mice, disclosing an unexpectedly strong reliance of cone photoreceptors on the RPE-based visual cycle. These data reveal a dominant role for RPE-CRALBP in supporting rod and cone function and highlight the importance of RPE cell targeting for CRALBP gene therapies.
Topics: Animals; Mice; Carrier Proteins; Ependymoglial Cells; Mice, Inbred C57BL; Mice, Knockout; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinal Pigments; Retinal Rod Photoreceptor Cells; Male; Female
PubMed: 38676924
DOI: 10.1016/j.celrep.2024.114143 -
International Journal of Molecular... Sep 2023Leaf senescence is an important factor affecting the functional transition from nutrient assimilation to nutrient remobilization in crops. The senescence of wheat leaves...
Leaf senescence is an important factor affecting the functional transition from nutrient assimilation to nutrient remobilization in crops. The senescence of wheat leaves is of great significance for its yield and quality. In the leaf senescence process, transcriptional regulation is a committed step in integrating various senescence-related signals. Although the plant-specific transcriptional regulation factor valine-glutamine (VQ) gene family is known to participate in different physiological processes, its role in leaf senescence is poorly understood. We isolated TaVQ25-A and studied its function in leaf senescence regulation. - was mainly expressed in the roots and leaves of wheat. The TaVQ25-A-GFP fusion protein was localized in the nuclei and cytoplasm of wheat protoplasts. A delayed senescence phenotype was observed after dark and abscisic acid (ABA) treatment in --silenced wheat plants. Conversely, overexpression of - accelerated leaf senescence and led to hypersensitivity in ABA-induced leaf senescence in . A WRKY type transcription factor, TaWRKY133, which is tightly related to the ABA pathway and affects the expression of some ABA-related genes, was found to interact with TaVQ25-A both in vitro and in vivo. Results of this study indicate that TaVQ25-A is a positive regulator of ABA-related leaf senescence and can be used as a candidate gene for wheat molecular breeding.
Topics: Triticum; Abscisic Acid; Plant Senescence; Nutrients; Glutamine; Arabidopsis
PubMed: 37762142
DOI: 10.3390/ijms241813839 -
Annals of Botany Oct 2023Dipteran insects are known pollinators of many angiosperms, but knowledge on how flies affect floral evolution is relatively scarce. Some plants pollinated by fungus...
BACKGROUND AND AIMS
Dipteran insects are known pollinators of many angiosperms, but knowledge on how flies affect floral evolution is relatively scarce. Some plants pollinated by fungus gnats share a unique set of floral characters (dark red display, flat shape and short stamens), which differs from any known pollination syndromes. We tested whether this set of floral characters is a pollination syndrome associated with pollination by fungus gnats, using the genus Euonymus as a model.
METHODS
The pollinator and floral colour, morphology and scent profile were investigated for ten Euonymus species and Tripterygium regelii as an outgroup. The flower colour was evaluated using bee and fly colour vision models. The evolutionary association between fungus gnat pollination and each plant character was tested using a phylogenetically independent contrast. The ancestral state reconstruction was performed on flower colour, which is associated with fungus gnat pollination, to infer the evolution of pollination in the genus Euonymus.
KEY RESULTS
The red-flowered Euonymus species were pollinated predominantly by fungus gnats, whereas the white-flowered species were pollinated by bees, beetles and brachyceran flies. The colour vision analysis suggested that red and white flowers are perceived as different colours by both bees and flies. The floral scents of the fungus gnat-pollinated species were characterized by acetoin, which made up >90 % of the total scent in three species. Phylogenetically independent contrast showed that the evolution of fungus gnat pollination is associated with acquisition of red flowers, short stamens and acetoin emission.
CONCLUSIONS
Our results suggest that the observed combination of floral characters is a pollination syndrome associated with the parallel evolution of pollination by fungus gnats. Although the role of the red floral display and acetoin in pollinator attraction remains to be elucidated, our finding underscores the importance of fungus gnats as potential contributors to floral diversification.
Topics: Bees; Animals; Pollination; Euonymus; Acetoin; Diptera; Fungi; Flowers
PubMed: 37610846
DOI: 10.1093/aob/mcad081