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ADP-Ribosylation Factor-Like 2 (ARL2) regulates cilia stability and development of outer segments in rod photoreceptor neurons
摘要： Photoreceptor cells are specialized neurons with a sensory cilium carrying an elaborate membrane structure, the outer segment (OS). Inherited mutations in genes involved in ciliogenesis frequently result in OS malformation and blindness. ADP-ribosylation factor-like 2 (ARL2) has recently been implicated in OS formation through its association with Binder of ARL2 (BART or ARL2BP), a protein linked to inherited blinding disease. To test the role of ARL2 in vision we created a transgenic mouse model expressing a tagged-dominant active form of human ARL2 (ARL2-Q70L) under a rod-specific promoter. Transgenic ARL2-Q70L animals exhibit reduced photoreceptor cell function as early as post-natal day 16 and progressive rod degeneration. We attribute loss of photoreceptor function to the defective OS morphogenesis in the ARL2-Q70L transgenic model. ARL2-Q70L expression results in shortened inner and outer segments, shortened and mislocalized axonemes and cytoplasmic accumulation of rhodopsin. In conclusion, we show that ARL2-Q70L is crucial for photoreceptor neuron sensory cilium development. Future research will expand upon our hypothesis that ARL2-Q70L mutant interferes with microtubule maintenance and tubulin regulation resulting in impaired growth of the axoneme and elaboration of the photoreceptor outer segment.
关键词： cilia,outer segment,ARL2,photoreceptor,retinal degeneration,ADP-ribosylation factor-like 2
更新于2025-09-10 09:29:36
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Induction of rod versus cone photoreceptor-specific progenitors from retinal precursor cells
摘要： During development, multipotent progenitors undergo temporally-restricted differentiation into post-mitotic retinal cells; however, the mechanisms of progenitor division that occurs during retinogenesis remain controversial. Using clonal analyses (lineage tracing and single cell cultures), we identify rod versus cone lineage-specific progenitors derived from both adult retinal stem cells and embryonic neural retinal precursors. Taurine and retinoic acid are shown to act in an instructive and lineage-restricted manner early in the progenitor lineage hierarchy to produce rod-restricted progenitors from stem cell progeny. We also identify an instructive, but lineage-independent, mechanism for the specification of cone-restricted progenitors through the suppression of multiple differentiation signaling pathways. These data indicate that exogenous signals play critical roles in directing lineage decisions and resulting in fate-restricted rod or cone photoreceptor progenitors in culture. Additional factors may be involved in governing photoreceptor fates in vivo.
关键词： Retina,Rod photoreceptor,Cone photoreceptor,Stem cell,Progenitors
更新于2025-09-09 09:28:46
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Photoreceptor actin dysregulation in syndromic and non-syndromic retinitis pigmentosa
摘要： Retinitis pigmentosa (RP) is the leading cause of inherited blindness. RP is a genetically heterogeneous disorder, with more than 100 different causal genes identified in patients. Central to disease pathogenesis is the progressive loss of retinal photoreceptors. Photoreceptors are specialised sensory neurons that exhibit a complex and highly dynamic morphology. The highly polarised and elaborated architecture of photoreceptors requires precise regulation of numerous cytoskeletal elements. In recent years, significant work has been placed on investigating the role of microtubules (specifically, the acetylated microtubular axoneme of the photoreceptor connecting cilium) and their role in normal photoreceptor function. This has been driven by the emerging field of ciliopathies, human diseases arising from mutations in genes required for cilia formation or function, of which RP is a frequently reported phenotype. Recent studies have highlighted an intimate relationship between cilia and the actin cytoskeleton. This review will focus on the role of actin in photoreceptors, examining the connection between actin dysregulation in RP.
关键词： Espin,RP2,Myosin VIIa,photoreceptor,CRB1,cytoskeleton,actin,Retinitis pigmentosa,Whirlin,FSCN2,cilia,RPGR,PROM1
更新于2025-09-09 09:28:46
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New Derivative Benzothiazole Suspend Diphenyleamine Based Aromatic Polyamides as Electrochromic Light Emitting Devices
摘要： In this work, a set of some substituted aromatic polyamides containing (benzothiazole)diphenylamine moieties (P1-P5) was prepared via the phosphorylation polycondensation technique from the reaction of several aromatic dicarboxylic acids with synthesized N,N-bis(4-aminophenyl)2-amine-6-methoxybenzothiazol (M). It was prepared from the cesium fluoride-mediated double N-arylation reaction of 6-methoxybenzothiazol (a) with p-fluoronitrobenzene to form dinitro intermediate (I) followed by palladium-catalyzed hydrazine reduction. FTIR, 1H and 13C NMR spectra techniques were utilized to characterize the chemical structures of all the resultant intermediates and polyamides. Thermal analysis revealed that the synthesized polyamides showed perfect thermal stability and superior glass transition temperatures (Tg). Dilute solutions of these polyamides in N-methyl pyrrolidone (10-5 M) showed good optical properties where exhibited intensive photoluminescence in the region of blue colour. Cyclic voltammograms of the synthesized polymers membrane molding onto the basis of ITO-plated glass in the spesial electrolyte contains 10-1 M of tetrabutylammonium perchlorate(TBAP) in dry CH3CN which exhibited one oxidation redox wave couples.
关键词： Polyamides,Photoluminescence,Electrochromic,Photoreceptor
更新于2025-09-09 09:28:46
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En Face Optical Coherence Tomography Imaging of the Photoreceptor Layers in Hydroxychloroquine Retinopathy
摘要： Objective: To investigate the application of en face optical coherence tomography (OCT) imaging in eyes with hydroxychloroquine (HCQ) retinopathy. Design: Retrospective case series Methods: Setting: Institutional Patient Population: Sixty-two eyes of 31 Asian patients with HCQ retinopathy. Observation Procedures: Macular volume scanning using swept-source OCT was performed in 6 × 6 and 9 × 9 mm areas centered on the fovea. Segmentation of the photoreceptor layers was automatically performed between the inner border of the ellipsoid zone and that of the retinal pigment epithelium-Bruch’s membrane complex to obtain en face OCT images. Findings from the en face images were qualitatively and quantitatively evaluated; they were analyzed and correlated with the fundus autofluorescence and visual field findings. Main Outcome Measures: En face OCT findings Results: All eyes with HCQ retinopathy had a beaten-bronze appearance in the areas with photoreceptor defects, whereas those with intact photoreceptors had areas with smooth surfaces, which were occasionally demarcated by hyporeflective margins, on the en face OCT images. The presence and extent of the retinopathy could be quickly determined using the images. They also provided quantitative information on the progression based on the areas of intact photoreceptors compared over several visits. Furthermore, the area of central intact photoreceptors significantly correlated with the mean deviation, pattern standard deviation, and visual field index of 30-2 visual field examinations (all P < .001). Conclusions: En face OCT may be useful for visualizing the presence and extent of HCQ retinopathy and its progression. The area of central intact photoreceptors measured on en face OCT images showed a significant association with functional visual field defects. This imaging may be a helpful adjunct for screening and follow-up examinations of HCQ retinopathy.
关键词： screening,en face optical coherence tomography,photoreceptor layers,progression,hydroxychloroquine retinopathy
更新于2025-09-09 09:28:46
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Synthesized glucocorticoid-induced leucine zipper peptide (GILZ-P) inhibits photoreceptor apoptosis and protects retinal function in light-induced retinal degeneration model
摘要： Background: This study aimed to investigate the neuroprotective function of a synthesized glucocorticoid-induced leucine zipper peptide (GILZ-p) in a light-induced retinal degeneration model. Methods: The GILZ98–134 peptide was synthesized and injected intravitreally into Sprague Dawley rats. Retinal injury was then induced in the rats by exposing their eyes to constant white light (5000 lux) for 24 h. The activation of retinal caspases-9/3 and the release of cytochrome c from the mitochondria to the cytosol were measured at 1, 3, 5 and 7 days after light injury. Photoreceptor apoptosis was evaluated with TUNEL staining at 3 days after injury. Hematoxylin and eosin staining and electroretinography were used to observe the changes in the retinal morphology and function, respectively, 7 and 14 days after light injury. Results: The intravitreally injected synthesized GILZ-p successfully penetrated to the retina and significantly inhibited the activation of retinal caspase-3 and caspase-9 at 1, 3, 5, and 7 days after light injury, and reduced the number of TUNEL-positive photoreceptors at 3 days after light injury. GILZ-p pretreatment also alleviated cytochrome c release and rescued mitochondria-mediated apoptosis after injury. Simultaneously, GILP-p pretreatment also mitigated the light-induced thinning of the outer nuclear layer and the loss of retinal function at 7 and 14 days after light injury, respectively. Conclusion: The synthesized GILZ-p prevented light-induced photoreceptor apoptosis and protected retinal function from degeneration, and is therefore a potential therapeutic option for degenerative retinal diseases.
关键词： photoreceptor,retinal degeneration,synthesized peptide,apoptosis,GILZ
更新于2025-09-09 09:28:46
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Immunolocalization suggests a role of the histamine-gated chloride channel PxHCLB in spectral opponent processing in butterfly photoreceptors
摘要： Spectrally opponent responses, that is, wavelength-dependent inversions of response polarity, have been observed at the level of photoreceptors in butterflies. As inter-photoreceptor connections have been found in the butterfly Papilio xuthus, and histamine is the only neurotransmitter so far identified in insect photoreceptors, we hypothesize that histaminergic sign-inverting synapses exist in the lamina between different spectral receptors as a mechanism for spectral opponency as in the medulla of Drosophila. Here, we localized two histamine-gated chloride channels, PxHCLA (Drosophila Ort homolog) and PxHCLB (Drosophila HisCl1 homolog), in the visual system of Papilio xuthus by using specific antisera. The antiPxHCLA labeling was associated with the membrane of nonphotoreceptor cells that are postsynaptic to photoreceptors, while the antiPxHCLB labeling overlapped with photoreceptor axons, indicating that PxHCLB is expressed at inter-photoreceptor synapses: PxHCLB is likely involved in producing spectral opponency at the first visual synapses. Color processing in Papilio may appear earlier than previously hypothesized in insect visual systems.
关键词： histamine receptor,RRID:AB_2737353,compound eye,photoreceptor,medulla,lamina,RRID:AB_260435,RRID:AB_2737352,RRID:AB_2737354,insect,RRID:AB_528479
更新于2025-09-09 09:28:46
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An N-Terminal ER Export Signal Facilitates the Plasma Membrane Targeting of HCN1 Channels in Photoreceptors
摘要： PURPOSE. Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels are widely expressed in the retina. In photoreceptors, the hyperpolarization-activated current (Ih) carried by HCN1 is important for shaping the light response. It has been shown in multiple systems that traf?cking HCN1 channels to speci?c compartments is key to their function. The localization of HCN1 in photoreceptors is concentrated in the plasma membrane of the inner segment (IS). The mechanisms controlling this localization are not understood. We previously identi?ed a di-arginine endoplasmic reticulum (ER) retention motif that negatively regulates the surface targeting of HCN1. In this study, we sought to identify a forward traf?cking signal that could counter the function of the ER retention signal. METHODS. We studied traf?cking of HCN1 and several mutants by imaging their subcellular localization in transgenic X. laevis photoreceptors. Velocity sedimentation was used to assay the assembly state of HCN1 channels. RESULTS. We found the HCN1 N-terminus can redirect a membrane reporter from outer segments (OS) to the plasma membrane of the IS. The sequence necessary for this behavior was mapped to a 20 amino acid region containing a leucine-based ER export motif. The ER export signal is necessary for forward traf?cking but not channel oligomerization. Moreover, this ER export signal alone counteracted the di-arginine ER retention signal. CONCLUSIONS. We identi?ed an ER export signal in HCN1 that functions with the ER retention signal to maintain equilibrium of HCN1 between the endomembrane system and the plasma membrane.
关键词： forward-traf?c motifs,localization,voltage-dependent Kt channels,inner segment,motif,neuron,signal targeting,ER export,hyperpolarization gated channels,retina,plasma membrane,photoreceptor
更新于2025-09-09 09:28:46
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Degeneration of Photoreceptor Cells in Arylsulfatase G-Deficient Mice
摘要： Retinal degeneration is a common feature of several lysosomal storage disorders, including the mucopolysaccharidoses, a group of metabolic disorders that is characterized by widespread accumulation of glycosaminoglycans due to lysosomal enzyme dysfunction. We used a new mouse model of mucopolysaccharidosis IIIE to study the effect of Arylsulfatase G (ARSG) deficiency on retina integrity. The retina of Arsg knockout mice aged 1 to 24 months was studied by immunohistochemistry and Western blot analysis. Electron microscopic analyses were performed on retinas from 15- and 22-month-old animals. Photoreceptor and microglia cell numbers and retina thickness were determined to quantitatively characterize retinal degeneration in ARSG-deficient mice. Arsg knockout mice showed a progressive degeneration of photoreceptor cells starting between 1 and 6 months of age, resulting in the loss of more than 50% of photoreceptor cells in 24-month-old mice. Photoreceptor loss was accompanied by reactive astrogliosis, reactive microgliosis that was evident in the outer but not inner retina, and elevated expression levels of some lysosomal proteins. Electron microscopic analyses of retinas revealed no evidence for the presence of storage vacuoles. Of note, expression of ARSG protein in wild-type mice was detectable only in the RPE which, however, appeared morphologically unaffected in knockout mice at the electron microscopic level. To our knowledge, this is the first study demonstrating that ARSG deficiency results in progressive photoreceptor degeneration and dysregulation of various lysosomal proteins.
关键词： Sanfilippo syndrome,mucopolysaccharidosis,retinal pigment epithelium,Arylsulfatase G,retina,neurodegeneration,photoreceptor cells
更新于2025-09-09 09:28:46
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Spatio-temporal regulation of Rx and mitotic patterns shape the eye-cup of the photoreceptor cells in Ciona
摘要： The ascidian larva has a pigmented ocellus comprised of a cup-shaped array of approximately 30 photoreceptor cells, a pigment cell, and three lens cells. Morphological, physiological and molecular evidence has suggested evolutionary kinship between the ascidian larval photoreceptors and vertebrate retinal and/or pineal photoreceptors. Rx, an essential factor for vertebrate photoreceptor development, has also been suggested to be involved in the development of the ascidian photoreceptor cells, but a recent revision of the photoreceptor cell lineage raised a crucial discrepancy between the reported expression patterns of Rx and the cell lineage. Here, we report spatio-temporal expression patterns of Rx at single-cell resolution along with mitotic patterns up to the final division of the photoreceptor-lineage cells in Ciona. The expression of Rx commences in non-photoreceptor a-lineage cells on the right side of the anterior sensory vesicle at the early tailbud stage. At the mid tailbud stage, Rx begins to be expressed in the A-lineage photoreceptor cell progenitors located on the right side of the posterior sensory vesicle. Thus, Rx is specifically but not exclusively expressed in the photoreceptor-lineage cells in the ascidian embryo. Two cis-regulatory modules are shown to be important for the photoreceptor-lineage expression of Rx. The cell division patterns of the photoreceptor-lineage cells rationally explain the generation of the cup-shaped structure of the pigmented ocellus. The present findings demonstrate the complete cell lineage of the ocellus photoreceptor cells and provide a framework elucidating the molecular and cellular mechanisms of photoreceptor development in Ciona.
关键词： Ascidian,Photoreceptor cell,Ciona,Rx,Morphogenesis
更新于2025-09-09 09:28:46