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Direct Regulation of Phytohormone Actions by Photoreceptors
摘要： Plants must adjust their growth and development adaptively in response to light. Four recent studies have now established novel paradigms connecting light and hormone signaling pathways, in which photoreceptors adopt three modes to directly regulate internal hormonal responses to external stimuli. Being sessile organisms, plants are equipped with the capacity to sense environmental information and adjust their growth and development accordingly. Light is one of the most important environmental factors, and exposure to light widely and profoundly regulates plant developmental processes (known as photomorphogenesis). To precisely sense the light signal, plants employ a series of photoreceptors across the spectrum of light. The red/far-red light (600–750 nm) receptors are members of phytochrome family, which contains five members (phyA to phyE) in arabidopsis (Arabidopsis thaliana). Cryptochromes, phototropins, and the ZEITLUPE family members sense the blue light (350–500 nm). UVR8 (UV RESISTANCE LOCUS 8) is the UV-B light (275–320 nm) receptor for UV-B responses. Plants track the status of their light environment, transduce the signals to the nucleus, and ultimately direct gene expression changes to induce light responses. Without developing a nervous system, plants have evolved phytohormones which act as internal chemical messengers for multicellular communication and coordinating plant growth and development in adaptation to various environmental conditions.
关键词： phytohormones,photomorphogenesis,photoreceptors,hormone signaling,light signaling
更新于2025-09-23 15:21:21
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Ultrahigh Resolution Mouse Optical Coherence Tomography to Aid Intraocular Injection in Retinal Gene Therapy Research
摘要： HR-SD-OCT is utilized to monitor the progression of photoreceptor degeneration in live mouse models, assess the delivery of therapeutic agents into the subretinal space, and to evaluate toxicity and efficacy in vivo. HR-SD-OCT uses near infrared light (800-880 nm) and has optics specifically designed for the unique optics of the mouse eye with sub-2-micron axial resolution. Transgenic mouse models of outer retinal (photoreceptor) degeneration and controls were imaged to assess the disease progression. Pulled glass microneedles were used to deliver sub retinal injections of adeno-associated virus (AAV) or nanoparticles (NP) via a trans-scleral and trans-choroidal approach. Careful positioning of the needle into the subretinal space was required prior to a calibrated pressure injection, which delivers fluid into the sub retinal space. Real time subretinal surgery was conducted on our retinal imaging system (RIS). HR-SD-OCT demonstrated progressive uniform retinal degeneration due to expression of a toxic mutant human mutant rhodopsin (P347S) (RHOP347S) transgene in mice. HR-SD-OCT allows rigorous quantification of all the retinal layers. Outer nuclear layer (ONL) thickness and photoreceptor outer segment length (OSL) measurements correlate with photoreceptor vitality, degeneration, or rescue. The RIS delivery system allows real-time visualization of subretinal injections in neonatal (~P10-14) or adult mice, and HR-SD-OCT immediately determines success of delivery and maps areal extent. HR-SD-OCT is a powerful tool that can evaluate the success of subretinal surgery in mice, in addition to measuring vitality of photoreceptors in vivo. HR-SD-OCT can also be used to identify uniform animal cohorts to evaluate the extent of retinal degeneration, toxicity, and therapeutic rescue in preclinical gene therapy research studies.
关键词： Optical Coherence Tomography,Retinal Degeneration,Imaging,Real-time,Retina,Microscope,Intraocular Injection,Preclinical,In Vivo,Photoreceptors,Greenough Stereo Microscopy,Sub-retinal
更新于2025-09-23 15:21:01
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Mechanisms Underlying the Visual Benefit of Cell Transplantation for the Treatment of Retinal Degenerations
摘要： The transplantation of retinal cells has been studied in animals to establish proof of its potential benefit for the treatment of blinding diseases. Photoreceptor precursors have been grafted in animal models of Mendelian-inherited retinal degenerations, and retinal pigmented epithelial cells have been used to restore visual function in animal models of age-related macular degeneration (AMD) and recently in patients. Cell therapy over corrective gene therapy in inherited retinal degeneration can overcome the genetic heterogeneity by providing one treatment for all genetic forms of the diseases. In AMD, the existence of multiple risk alleles precludes a priori the use of corrective gene therapy. Mechanistically, the experiments of photoreceptor precursor transplantation reveal the importance of cytoplasmic material exchange between the grafted cells and the host cells for functional rescue, an unsuspected mechanism and novel concept. For transplantation of retinal pigmented epithelial cells, the mechanisms behind the therapeutic benefit are only partially understood, and clinical trials are ongoing. The fascinating studies that describe the development of methodologies to produce cells to be grafted and demonstrate the functional benefit for vision are reviewed.
关键词： retinitis pigmentosa,photoreceptors,retinal pigmented epithelium,age-related macular degeneration,cytoplasmic material transfer,induced-pluripotent stem cells
更新于2025-09-19 17:15:36
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Henle Fiber Layer Phase Retardation Changes Associated With Age-Related Macular Degeneration
摘要： PURPOSE. To quantify and compare phase retardation amplitude and regularity associated with the Henle fiber layer (HFL) between nonexudative AMD patients and age-matched controls using scanning laser polarimetry (SLP) imaging. METHODS. A scanning laser polarimeter was used to collect 15 × 15° macular-centered images in 25 patients with nonexudative AMD and 25 age-matched controls. Raw image data were used to compute macular phase retardation maps associated with the HFL. Consecutive, annular regions of interest from 0.5 to 3.0° eccentricity, centered on the fovea, were used to generate intensity profiles from phase retardation data and analyzed with two complementary techniques: a normalized second harmonic frequency (2f) of the fast Fourier Transform (FFT) analysis and a curve fitting analysis using a 2f sine function. Paired t-tests were used to compare the normalized 2f FFT magnitude at each eccentricity between the two groups, the eccentricity that yielded the maximum normalized 2f FFT between paired individuals across the two groups, and curve fitting RMS error at each eccentricity between the two groups. RESULTS. Normalized 2f FFT components were lower in the AMD group at each eccentricity, with no difference between the two groups in the maximum normalized 2f FFT component eccentricity. The root-mean-square (RMS) error from curve fitting was significantly higher in the AMD group. CONCLUSIONS. Phase retardation changes in the central macula indicate loss and/or structural alterations to central cone photoreceptors in nonexudative AMD patients. Scanning laser polarimetry imaging is a noninvasive method for quantifying cone photoreceptor changes associated with central macular disease.
关键词： scanning laser polarimetry,age-related macular degeneration,Henle fiber layer,photoreceptors
更新于2025-09-19 17:15:36
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Electrical activation of degenerated photoreceptors in blind mouse retina elicited network-mediated responses in different types of ganglion cells
摘要： Electrical (e-) stimulation is explored in schemes to rescue the vision of blind people, e.g. those affected by Retinitis Pigmentosa (RP). We e-activated subretinally the surviving degenerated photoreceptors (d-Phrs) of the rd1 mouse (RP model) and evoked visual responses in the blind retina. The e-stimulation was applied with a single platinum/iridium electrode. The d-Phrs (calcium-imaging) and ganglion cells (GC) activity (MEA-recording) were recorded in simultaneous multilayer recordings. The findings of this study confirm that the d-Phrs responded to e-stimulation and modulated the retinal network-activity. The application of blockers revealed that the synaptic interactions were dependent on voltage-gated calcium channels and mediated by the transmitters glutamate and GABA. Moreover, the gap junctions coupled networks promoted the lateral-spread of the e-evoked activity in the outer (~60 μm) and inner (~120 μm) retina. The activated GCs were identified as subtypes of the ON, OFF and ON-OFF classes. In conclusion, d-Phrs are the ideal interface partners for implants to elicit enhanced visual responses at higher temporal and spatial resolution. Furthermore, the retina’s intact circuity at the onset of complete blindness makes it a tempting target when considering the implantation of implants into young patients to provide a seamless transition from blinding to chip-aided vision.
关键词： blind retina,MEA recording,subretinal implant,gap junctions,glutamate,rd1 mouse,calcium imaging,ganglion cells,GABA,electrical stimulation,Retinitis Pigmentosa,degenerated photoreceptors
更新于2025-09-19 17:15:36
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Soluble Adenylyl Cyclase Is Required for Retinal Ganglion Cell and Photoreceptor Differentiation
摘要： PURPOSE. We have previously demonstrated that soluble adenylyl cyclase (sAC) is necessary for retinal ganglion cell (RGC) survival and axon growth. Here, we further investigate the role of sAC in neuronal differentiation during retinal development. METHODS. Chx10 or Math5 promoter-driven Cre-Lox recombination were used to conditionally delete sAC from early and intermediate retinal progenitor cells during retinal development. We examined cell type–specific markers expressed by retinal cells to estimate their relative numbers and characterize retinal laminar morphology by immunofluorescence in adult and newborn mice. RESULTS. Retinal ganglion cell and amacrine cell markers were significantly lower in the retinas of adult Math5cre/sAC fl/fl and Chx10cre/sAC fl/fl mice than in those of wild-type controls. The effect on RGC development was detectable as early as postnatal day 1 and deleting sAC in either Math5- or Chx10-expressing retinal progenitor cells also reduced nerve fiber layer thickness into adulthood. The thickness of the photoreceptor layer was slightly but statistically significantly decreased in both the newborn Chx10cre/sAC fl/fl and Math5cre/sAC fl/fl mice, but this reduction and abnormal morphology persisted in the adults in only the Chx10cre/sAC fl/fl mice. CONCLUSIONS. sAC plays an important role in the early retinal development of RGCs as well as in the development of amacrine cells and to a lesser degree photoreceptors.
关键词： photoreceptors,soluble adenylyl cyclase,retinal development,amacrine cell,retinal ganglion cell
更新于2025-09-19 17:15:36
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Temporal resolution of single photon responses in primate rod photoreceptors and limits imposed by cellular noise
摘要： Sensory receptor noise corrupts sensory signals, contributing to imperfect perception and dictating central processing strategies. For example, noise in rod phototransduction limits our ability to detect light and minimizing the impact of this noise requires precisely tuned nonlinear processing by the retina. But detection sensitivity is only one aspect of night vision: prompt and accurate behavior also requires that rods reliably encode the timing of photon arrivals. We show here that the temporal resolution of responses of primate rods is much finer than the duration of the light response and identify the key limiting sources of transduction noise. We also find that the thermal activation rate of rhodopsin is lower than previous estimates, implying that other noise sources are more important than previously appreciated. A model of rod single-photon responses reveals that the limiting noise relevant for behavior depends critically on how rod signals are pooled by downstream neurons.
关键词： thermal activation rate,primate rod photoreceptors,single photon responses,cellular noise,rhodopsin,temporal resolution
更新于2025-09-11 14:15:04
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Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes
摘要： PURPOSE. Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin(cid:2)/(cid:2) and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes. METHODS. Retinal thickness, superoxide, expression of in?ammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods. RESULTS. Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration. CONCLUSIONS. Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This ?nding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration.
关键词： opsin,retina,microvasculature,photoreceptors
更新于2025-09-11 14:15:04
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Localizing proton-mediated inhibitory feedback at the retinal horizontal cell-cone synapse with genetically-encoded pH probes
摘要： Lateral inhibition in the vertebrate retina depends on a negative feedback synapse between horizontal cells (HCs) and rod and cone photoreceptors. A change in pH is thought to be the signal for negative feedback, but its spatial profile in the synaptic cleft is unknown. Here we use 3 different membrane proteins, each fused to the same genetically-encoded pH-sensitive GFP (pHluorin), to probe synaptic pH in retina from transgenic zebrafish (Danio rerio) of either sex. We used the cone transducin promoter to express SynaptopHluorin (pHluorin on VAMP2) or CalipHluorin (pHluorin on an L-type Ca2+ channel) and the HC-specific connexin-55.5 promoter to express AMPApHluorin (pHluorin on an AMPA receptor). Stimulus light led to increased fluorescence of all three probes, consistent with alkalinization of the synaptic cleft. The receptive field size, sensitivity to surround illumination, and response to activation of an alien receptor expressed exclusively in HCs, are consistent with lateral inhibition as the trigger for alkalinization. However, SynaptopHluorin and AMPApHluorin, which are displaced farther from cone synaptic ribbons than CalipHlourin, reported a smaller pH change. Hence, unlike feed-forward glutamatergic transmission, which spills over to allow cross-talk between terminals in the cone network, the pH change underlying HC feedback is compartmentalized to individual synaptic invaginations within a cone terminal, consistent with private line communication.
关键词： lateral inhibition,zebrafish,cone photoreceptors,pHluorin,horizontal cells,synaptic pH,retina
更新于2025-09-11 14:15:04
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Determination of Rod and Cone Influence to the Early and Late Dynamic of the Pupillary Light Response
摘要： PURPOSE. This study aims to identify which aspects of the pupil light re?ex are most in?uenced by rods and cones independently by analyzing pupil recordings from different mouse models of photoreceptor de?ciency. METHODS. One-month-old wild type (WT), rodless (Rho(cid:2)/(cid:2)), coneless (Cnga3(cid:2)/(cid:2)), or photoreceptor less (Cnga3(cid:2)/(cid:2); Rho(cid:2)/(cid:2) or Gnat1(cid:2)/(cid:2)) mice were subjected to brief red and blue light stimuli of increasing intensity. To describe the initial dynamic response to light, the maximal pupillary constriction amplitudes and the derivative curve of the ?rst 3 seconds were determined. To estimate the postillumination phase, the constriction amplitude at 9.5 seconds after light termination was related to the maximal constriction amplitude. RESULTS. Rho(cid:2)/(cid:2) mice showed decreased constriction amplitude but more prolonged pupilloconstriction to all blue and red light stimuli compared to wild type mice. Cnga3(cid:2)/(cid:2) mice had constriction amplitudes similar to WT however following maximal constriction, the early and rapid dilation to low intensity blue light was decreased. To high intensity blue light, the Cnga3(cid:2)/(cid:2) mice demonstrated marked prolongation of the pupillary constriction. Cnga3(cid:2)/(cid:2); Rho(cid:2)/(cid:2) mice had no pupil response to red light of low and medium intensity. CONCLUSIONS. From speci?c gene defective mouse models which selectively voided the rod or cone function, we determined that mouse rod photoreceptors are highly contributing to the pupil response to blue light stimuli but also to low and medium red stimuli. We also observed that cone cells mainly drive the partial rapid dilation of the initial response to low blue light stimuli. Thus photoreceptor dysfunction can be derived from chromatic pupillometry in mouse models.
关键词： pupillary response,photoreceptors,mouse model,retinal dystrophy
更新于2025-09-11 14:15:04