Rod Outer Segments Research Articles

Rod function deficit in retained photoreceptors of patients with class B Rhodopsin mutations

A common inherited retinal disease is caused by mutations in RHO expressed in rod photoreceptors that provide vision in dim ambient light. Approximately half of all RHO mutations result in a Class B phenotype where mutant rods are retained in some retinal regions but show severe degeneration in other regions. We determined the natural history of dysfunction and degeneration of retained rods by serially evaluating patients. Even when followed for more than 20 years, rod function and structure at some retinal locations could remain unchanged. Other locations showed loss of both vision and photoreceptors but the rate of rod vision loss was greater than the rate of photoreceptor degeneration. This unexpected divergence in rates with disease progression implied the development of a rod function deficit beyond loss of cells. The divergence of progression rates was also detectable over a short interval of 2 years near the health-disease transition in the superior retina. A model of structure–function relationship supported the existence of a large rod function deficit which was also most prominent near regions of health-disease transition. Our studies support the realistic therapeutic goal of improved night vision for retinal regions specifically preselected for rod function deficit in patients.

ROM1 contributes to phenotypic heterogeneity in PRPH2-associated retinal disease.

Peripherin 2 (PRPH2) is a retina-specific tetraspanin protein essential for the formation of rod and cone photoreceptor outer segments (OS). Patients with mutations in PRPH2 exhibit severe retinal degeneration characterized by vast inter- and intra-familial phenotypic heterogeneity. To help understand contributors to this within-mutation disease variability, we asked whether the PRPH2 binding partner rod OS membrane protein 1 (ROM1) could serve as a phenotypic modifier. We utilized knockin and transgenic mouse models to evaluate the structural, functional and biochemical effects of eliminating one allele of Rom1 (Rom1+/-) in three different Prph2 models which mimic human disease: C213Y Prph2 (Prph2C/+), K153Del Prph2 (Prph2K/+) and R172W (Prph2R172W). Reducing Rom1 in the absence of Prph2 mutations (Rom1+/-) had no effect on retinal structure or function. However, the effects of reducing Rom1 in the presence of Prph2 mutations were highly variable. Prph2K/+/Rom1+/- mice had improved rod and cone function compared with Prph2K/+ as well as amelioration of K153Del-associated defects in PRPH2/ROM1 oligomerization. In contrast, Prph2R172W/Rom1+/- animals had worsened rod and cone function and exacerbated retinal degeneration compared with Prph2R172W animals. Removing one allele of Rom1 had no effect in Prph2C/+. Combined, our findings support a role for non-pathogenic ROM1 null variants in contributing to phenotypic variability in mutant PRPH2-associated retinal degeneration. Since the effects of Rom1 reduction are variable, our data suggest that this contribution is specific to the type of Prph2 mutation.

Cofilin Inhibition by Limk1 Reduces Rod Formation and Cell Apoptosis after Ischemic Stroke

Cofilin, a cytoskeletal actin severing protein, is essential for the initiation phase of apoptosis. The formation of cofilin rods (containing 1:1 cofilin:actin) has been studied in cultured mammalian neurons under conditions of excessive glutamate, ATP depletion (ATP-D) or oxidative stress. These conditions simulate the pathologies occurring during ischemic stroke. In this study, we investigated the potential involvement of cofilin during ischemic-stroke induced apoptosis. Transient middle cerebral artery occlusion (tMCAO) was performed to establish an experimental model of ischemic stroke. We used 2,3,5-Triphenyltetrazolium Chloride (TTC) and immunostaining of the neuronal marker neuronal nuclei (NeuN) to evaluate the evolving phases of infarction in rats subjected tMCAO. Immunostaining and TdT-mediated dUTP Nick-End Labeling (TUNEL) apoptosis staining were collaboratively used to examine cofilin rod formation and cell apoptosis in response to ischemia at different time points (2 h, 8 h, 24 h and 7 d). Our results showed that infarct volume increased initially, between the first 2 h to 24 h and became stabilized 24 h to 7 d after tMCAO. The formation of cofilin rods significantly increased in the cortical core (from 2 h) and penumbra (from 8 h), peaking at 24 h and gradually diminishing 7 d after tMCAO. Progressive accumulation of cofilin rods subsequently induced microtubule-associated protein-2 (MAP2) degradation and ischemic cell apoptosis in the infarct cortex after stroke. To further corroborate the role of activated cofilin in ischemic stroke, inhibition of cofilin by LIM kinase (Limk1) over-expression was performed. Lmik1 reduced cofilin rod formation and MAP2 degradation, and consequently, attenuated cofilin mediated-apoptosis 24 h after tMCAO. From this evidence we conclude that cofilin plays a role in the onset of ischemic-induced apoptosis and may be efficacious in future studies as a drug target for ischemic stroke.

Retinal photoreceptor damage produced in guinea pigs by tunicamycin.

Corynetoxins, members of the tunicamycin group of antibiotics, produce a severe and frequently fatal neurological disorder in ruminant livestock, and guinea pigs are a useful model to study the pathology and pathogenesis of this disease. The aim of this study was to determine whether tunicamycin produced ocular damage in this species, which could have pharmacotherapeutic and diagnostic value. Four 8-week-old guinea pigs were treated with tunicamycin, and two control animals were given the drug vehicle only. Guinea pigs were injected subcutaneously with 400 μg/kg of tunicamycin, in dimethyl sulphoxide, and killed 48 h post-injection. The eyes were then examined by light microscopy. Immunohistochemistry for rhodopsin was also performed. The principal pathological finding was marked retinal photoreceptor damage, which was characterised by disruption and disorganisation of rods, sometimes progressing to necrosis and separation of the outer segment. The cytoplasm of some rods was focally distended by accumulated, proteinaceous material. Rhodopsin immunopositivity in injured rods was markedly diminished and associated with shrinkage and shortening of the injured rod's outer segment. Ocular pathology, in the form of reproducible and extensive retinal photoreceptor damage, was found in guinea pigs given tunicamycin, extending the range of species found to be susceptible to this toxic injury. The guinea pig could prove to be a good animal model to test potential therapeutic interventions, and as brain lesions are often minimal and liver pathology non-specific in intoxicated ruminants, any spontaneously arising ophthalmic injury found in these species could be diagnostically useful.

Effect of AAV-Mediated Rhodopsin Gene Augmentation on Retinal Degeneration Caused by the Dominant P23H Rhodopsin Mutation in a Knock-In Murine Model.

Mutations in the rhodopsin gene may cause photoreceptor degeneration in autosomal dominant retinitis pigmentosa (ADRP) by dominant negative or toxic gain-of-function mechanisms. Controversy exists as to the mechanism by which the widely studied P23H mutation induces rod cell dysfunction and death. Inherited disease caused by dominant negative mutations may be amenable to treatment using wild-type gene augmentation. Indeed, prior studies in the RHOP23H, Rho+/- transgenic mouse model of ADRP have suggested that a therapeutic benefit may be achieved when wild-type rhodopsin is overexpressed following subretinal delivery of a recombinant adeno-associated viral (AAV) vector. In this study, we investigated the effect of wild-type rhodopsin supplementation on the rate of retinal degeneration in the more clinically relevant RhoP23H/+ knock-in mouse model of ADRP. Four AAVs carrying the human rhodopsin coding sequence were first designed and compared for efficacy in the rhodopsin knockout mouse. All four vectors were capable of driving expression of the human transgene in the knockout retina with the protein being appropriately trafficked to de novo rod outer segments. The most efficient of these vectors was injected at one of two doses into the subretinal space of RhoP23H/+ mice and the effect on retinal structure and function determined longitudinally by spectral-domain optical coherence tomography and electroretinography, respectively, over a 3-month period. Although significant overexpression of rhodopsin protein was achieved in this model, no beneficial effect on retinal structure or function was observed at either dose. Lack of therapeutic efficacy in this model may be attributable to the relative rapidity of degeneration in the RhoP23H/+ mouse relative to the human disease, over- or under dosing at the level of individual photoreceptors, late timing of the intervention, or a possible predominant toxic gain-of-function mechanism of degeneration.

Cross-linking of bovine rhodopsin with sulfosuccinimidyl 4-(N maleimidomethyl)cyclohexane-1-carboxylate affects its functionality.

Rhodopsin is the photoreceptor protein involved in visual excitation in retinal rods. The functionality of bovine rhodopsin was determined following treatment with sulfosuccinimidyl 4-(N maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC), a bifunctional reagent capable of forming covalent cross-links between suitable placed lysines and cysteines. Denaturing polyacrylamide gel electrophoresis showed that rhodopsin incubated with sulfo-SMCC generated intermolecular dimers, trimers, and higher oligomers, although most of the sulfo-SMCC-treated protein remained as a monomer. Minor alterations on the absorption spectrum of light-activated sulfo-SMCC-treated rhodopsin were observed. However, only ∼2% stimulation of the guanine nucleotide binding activity of transducin was measured in the presence of sulfo-SMCC-cross-linked photolyzed rhodopsin. Moreover, rhodopsin kinase was not able of phosphorylating sulfo-SMCC-cross-linked rhodopsin after illumination. Rhodopsin was purified in the presence of either 0.1% or 1% n-dodecyl β-d-maltoside, to obtain dimeric and monomeric forms of the protein, respectively. Interestingly, no generation of the regular F1 and F2 thermolytic fragments was perceived with sulfo-SMCC-cross-linked rhodopsin either in the dimeric or monomeric state, implying the formation of intramolecular connections in the protein that might thwart the light-induced conformational changes required for interaction with transducin and rhodopsin kinase. Structural analysis of the rhodopsin three-dimensional structure suggested that the following lysine and cysteine pairs: Lys66/Lys67 and Cys316, Cys140 and Lys141, Cys140 and Lys248, Lys311 and Cys316, and/or Cys316 and Lys325 are potential candidates to generate intramolecular cross-links in the protein. Yet, the lack of fragmentation of sulfo-SMCC-treated Rho with thermolysin is consistent with the formation of cross-linking bridges between Lys66/Lys67 and Cys316, and/or Cys140 and Lys248.

RNA sequencing analysis of the human retina and associated ocular tissues

The retina is a stratified layer of sensory neurons lining the posterior portion of the eye. In humans, fine detail and color vision are enabled by the macula, a central region of the retina dense in cone photoreceptors (PRs). Achromatic low light and peripheral vision are facilitated by rod PRs found with increasing density outside the macula in the peripheral retina. The outer retina is nourished by choroidal blood flow regulated by a single layer of intervening retinal pigment epithelial (RPE) cells. Existing human retinal transcriptome projects have been critical for studying aspects of retinal development and disease however, there are currently no publicly available data sets accurately describing the aging human central retina, peripheral retina, and supporting RPE/choroid. Here we used Illumina RNA sequencing (RNA-seq) analysis to characterize the mRNA transcriptome of rod and cone PR-enriched human retina as well as supporting macular RPE/choroid tissue. These data will be valuable to the vision research community for characterizing global changes in gene expression in clinically relevant ocular tissues.

Differential adaptations in rod outer segment disc membranes in different models of congenital stationary night blindness

Rod photoreceptor cells initiate scotopic vision when the light receptor rhodopsin absorbs a photon of light to initiate phototransduction. These photoreceptor cells are exquisitely sensitive and have adaptive mechanisms in place to maintain optimal function and to overcome dysfunctional states. One adaptation rod photoreceptor cells exhibit is in the packing properties of rhodopsin within the membrane. The mechanism underlying these adaptations is unclear. Mouse models of congenital stationary night blindness with different molecular causes were investigated to determine which signals are important for adaptations in rod photoreceptor cells. Night blindness in these mice is caused by dysfunction in either rod photoreceptor cell signaling or bipolar cell signaling. Changes in the packing of rhodopsin within photoreceptor cell membranes were examined by atomic force microscopy. Mice expressing constitutively active rhodopsin did not exhibit any adaptations, even under constant dark conditions. Mice with disrupted bipolar cell signaling exhibited adaptations, however, they were distinct from those in mice with disrupted phototransduction. These differential adaptations demonstrate that although multiple molecular defects can lead to a similar primary defect causing disease (i.e., night blindness), they can cause different secondary effects (i.e., adaptations). The lighting environment or signaling defects present from birth and during early rearing can condition mice and affect the adaptations occurring in more mature animals. A comparison of effects in wild-type mice, mice with defective phototransduction, and mice with defective bipolar cell signaling, indicated that bipolar cell signaling plays a role in this conditioning but is not required for adaptations in more mature animals.

Two Types of Cl Transporters Contribute to the Regulation of Intracellular Cl Concentrations in ON- and OFF-type Bipolar Cells in the Mouse Retina

In the retina, ON- and OFF-type bipolar cells are classified by subtype-specific center responses, which are attributed to differences in glutamate receptor subtypes. However, the mechanisms by which ON- and OFF-type bipolar cells generate subtype-specific surround responses remain unclear. One hypothesis for surround responses is that intracellular Cl concentrations ([Cl-]i) are set at different levels to achieve opposite polarities for GABA responses in ON- and OFF-type bipolar cells. Although this hypothesis is supported by previous findings obtained from rod (ON-) type bipolar cells, there is currently no information on OFF-type bipolar cells. In the present study, we examined the distribution and function of the Cl transporters, the Na-K-Cl co-transporter (NKCC1) and K-Cl co-transporter (KCC2), in rod (ON-) and OFF-type bipolar cells using immunohistochemical, in situ hybridization, and electrophysiological methods. Rod (ON-) and OFF-type bipolar cells both expressed NKCC1 and KCC2. However, the functional contribution of NKCC1 and KCC2 to the regulation of [Cl−]i differed between rod (ON-) and OFF-type bipolar cells. Strong NKCC1 activity increased [Cl−]i in rod (ON-) type bipolar cells, while that of KCC2 decreased [Cl−]i in OFF-type bipolar cells. We also confirmed the presence of a [Cl−]i gradient between dendrites and axon terminals in rod (ON-type) bipolar cells. Thus, the subtype-specific control of [Cl−]i is achieved by the activity of NKCC1 relative to that of KCC2 and appears to influence the polarity of surround responses.

Retinal Degeneration Caused by Rod-Specific Dhdds Ablation Occurs without Concomitant Inhibition of Protein N-Glycosylation.

SummaryDehydrodolichyl diphosphate synthase (DHDDS) catalyzes the committed step in dolichol synthesis. Recessive mutations in DHDDS cause retinitis pigmentosa (RP59), resulting in blindness. We hypothesized that rod photoreceptor-specific ablation of Dhdds would cause retinal degeneration due to diminished dolichol-dependent protein N-glycosylation. Dhddsflx/flx mice were crossed with rod-specific Cre recombinase-expressing (Rho-iCre75) mice to generate rod-specific Dhdds knockout mice (Dhddsflx/flx iCre+). In vivo morphological and electrophysiological evaluation of Dhddsflx/flx iCre+ retinas revealed mild retinal dysfunction at postnatal (PN) 4 weeks, compared with age-matched controls; however, rapid photoreceptor degeneration ensued, resulting in almost complete loss of rods and cones by PN 6 weeks. Retina dolichol levels were markedly decreased by PN 4 weeks in Dhddsflx/flx iCre+ mice, relative to controls; despite this, N-glycosylation of retinal proteins, including opsin (the dominant rod-specific glycoprotein), persisted in Dhddsflx/flx iCre+ mice. These findings challenge the conventional mechanistic view of RP59 as a congenital disorder of glycosylation.

Comparative exome sequencing reveals novel candidate genes for retinitis pigmentosa.

BackgroundRetinitis pigmentosa (RP) is the most common form of inherited retinal degeneration, but genetic defects in nearly half of families remain unresolved. This study aims to identify novel genes associated with RP based on whole exome sequencing (WES) data from 552 probands with RP.MethodsBiallelic loss-of-function (LoF) variants were selected from the WES data of 552 probands with RP and compared with that of 4728 in-house controls and the gnomAD database. Expression analysis and knockout mice model or knockdown zebrafish model were performed to confirm the association of a few candidate genes with RP.FindingsUnique biallelic LoF variants in ENSA, DACT2, DDR1, and CCDC188 were identified in four probands with RP, but were absent in 4728 in-house controls and were extremely rare in the gnomAD database. The expression of ENSA was enriched in the rod outer segments of human retina, and significant reduced responses of rods and cones were detected in Ensa knockout mice compared to wild-type mice by electroretinogram. The DACT2 transcript showed the highest expression in human retina and knockdown of dact2 in zebrafish resulted in photoreceptor disc membrane disarrangement.InterpretationThis study suggests that ENSA is likely a novel gene for RP and DACT2 is a potentially candidate gene for RP. Further studies are expected to evaluate the association between mutations in the other two genes and RP. To our knowledge, mutations in these genes have not been reported to be associated with RP before.

Constitutive Apo-Opsin Activity Across Retinal Cone Subtypes

Retinal rod and cone photoreceptors mediate vision in dim and bright light, respectively, by transducing absorbed photons into electrical signals. Their phototransduction mechanisms are essentially identical. However, one distinct difference between them is that, whereas a rod visual pigment remains stable in darkness, a cone pigment is liable to spontaneously dissociate into apo-opsin and retinal (the chromophore) without isomerization. This cone-pigment property has long been reported, but it has often been overlooked in the field. Importantly, because apo-opsin has constitutive activity, it triggers transduction signaling to produce electrical noise even in darkness. Currently, the precise apo-opsin content in dark-adapted cones is unknown, as is its associated dark activity. We report here a systematic study of red (L), green (M) and blue (S) cones, finding different percentages of apo-opsin across them in darkness. Surprisingly, we also found that apo-opsin signaling in L and M cones in darkness is actually much higher than the well-known holo-pigment thermal isomerization activity. As such, given the very low signal amplification at the pigment-to-transducin/phosphodiesterase step in cone transduction, apo-opsin noise may not be easily distinguishable from light-triggered responses and may affect cone vision near threshold.

Two-pathway anti-interference neural network based on the retinal perception mechanism for classification of remote sensing images from unmanned aerial vehicles

The ultrahigh resolution of unmanned aerial vehicle (UAV) remote sensing images and tilting photography with multiple perspectives provide complete and detailed ground observation data for various engineering applications. However, noise and interference information make learning the typical features of ground objects difficult for current deep learning semantic segmentation networks. The hierarchical cognitive structure of human vision and the information transmission modes of retinal cone and rod cells were used to design a two-pathway anti-interference network for retinal perception mechanism simulation (RPMS). In the first pathway, the hierarchical cognition of cone cells was simulated by a one-to-one connected multiscale dilated convolution structure. In the second pathway, the hierarchical cognition of rod cells was simulated by a multiscale pyramid structure with many-to-one connections. With the one-to-one connection, the ability of RPMS to recognize detailed edges was strengthened. Furthermore, the many-to-one connection helped RPMS resist the disturbance from noise and interference. By combining the feature maps of the two paths, RPMS exhibited stronger noise resistance, better texture recognition, and better detail recognition compared with other semantic segmentation networks in the classification experiments. Thus this technique is suitable for UAV remote sensing image classification and has a broad application potential.

Spectrally Selective Transformations of Solar Radiation by Retinal Photoreceptors in the Control of the Circadian Rhythm of the Human Body throughout an 11-Year Cycle of Solar Activity

Abstract—The round-the-day effect of solar radiation on photoreceptors of the retina of the eye and its role in the control of the circadian rhythm of the human body within an arbitrary 11-year cycle of solar activity are considered. Processed data describing the variation of the spectral and energy characteristics of solar radiation that reach the Earth’s surface over a solar activity cycle are given. On this basis, a generalized analytical expression has been obtained that models the spectrally selective processing of the sum of the direct and diffuse components of solar radiation by retinal rods and blue-sensitive (S type) cones. The obtained expression allows consideration of separate spectrally selective processing of the direct and diffuse components of solar radiation by rods and S cones of retina, including the case of a catastrophic lesion of one of the neuronal paths that connect rods or S cones with suprachiasmatic hypothalamus nuclei. It is shown that the effective spectrum obtained as a result of spectral selection of the components of solar radiation that is used to control the circadian activity of the human body is determined solely by the spectral sensitivity of rods and S cones. The effective spectrum does not depend on daily variations in the spectrum of solar radiation as the angular elevation of the Sun varies; the daily energy characteristics of the effective spectrum, which vary within each solar activity cycle, retain their dependence on the Sun’s elevation in the daytime and on the current phase of the solar activity cycle. Significant changes in the characteristics of solar radiation within the cycle of solar activity infer that it is necessary to take them into account in studying and modeling the control processes of human circadian activity driven by solar radiation.

Astragaloside IV protects retinal pigment epithelial cells from apoptosis by upregulating miR‑128 expression in diabetic rats.

The present study aimed to investigate the protective effects exerted by astragaloside-IV (AIV) on retinal pigment epithelial (RPE) cells of rats with diabetes mellitus (DM), and to explore the underlying molecular mechanisms. For this purpose, a rat model of DM was established by injecting rats with an intraperitoneal injection of streptozotocin. AIV was then intragastrically administered. An electroretinogram (ERG) was used to assess retinopathy and TUNEL staining was used to detect the level of apoptosis of RPE cells. Western blot analysis was used to determine protein expression in RPE cells in vitro and in vivo. AIV was found to be able to significantly increase body weight and decrease blood glucose levels in rats with DM in a dose-dependent manner. Compared with the rats with DM, the rat rod cell response a wave, b wave, maximum response b wave, photopic (photo)-ERG b wave and oscillatory potential (OP) p4 wave latency significantly decreased and the amplitude of OP Os1 wave increased significantly in the rats with DM treated with AIV for 11 weeks. In addition, AIV significantly decreased the apoptotic levels of RPE cells from rats with DM and significantly decreased the protein expression levels of Bax/Bcl-2, Fas/FasL, active caspase-3, active caspase-8, active caspase-9, homeobox B3 (HOXB3), p-phosphoinositide 3-kinase (PI3K)/PI3K, p-AKT/AKT and p-p70S6K1/p70S6K1, whereas it significantly increased miR-128 expression in the RPE cells from rats with DM. In vitro, AIV significantly inhibited the high glucose (HG)-induced apoptosis of RPE cells by increasing miR-128 expression and Bcl-2 and FasL protein expression in vivo. On the whole, the findings of the present study demonstrate that AIV treatment protects RPE cells of diabetic rats from apoptosis, and that these effects may be associated with the upregulation of miR-128 expression.

SARM1 deficiency promotes rod and cone photoreceptor cell survival in a model of retinal degeneration.

Retinal degeneration is the leading cause of incurable blindness worldwide and is characterised by progressive loss of light-sensing photoreceptors in the neural retina. SARM1 is known for its role in axonal degeneration, but a role for SARM1 in photoreceptor cell degeneration has not been reported. SARM1 is known to mediate neuronal cell degeneration through depletion of essential metabolite NAD and induction of energy crisis. Here, we demonstrate that SARM1 is expressed in photoreceptors, and using retinal tissue explant, we confirm that activation of SARM1 causes destruction of NAD pools in the photoreceptor layer. Through generation of rho -/- sarm1 -/- double knockout mice, we demonstrate that genetic deletion of SARM1 promotes both rod and cone photoreceptor cell survival in the rhodopsin knockout (rho -/- ) mouse model of photoreceptor degeneration. Finally, we demonstrate that SARM1 deficiency preserves cone visual function in the surviving photoreceptors when assayed by electroretinography. Overall, our data indicate that endogenous SARM1 has the capacity to consume NAD in photoreceptor cells and identifies a previously unappreciated role for SARM1-dependent cell death in photoreceptor cell degeneration.

PCARE and WASF3 regulate ciliary F-actin assembly that is required for the initiation of photoreceptor outer segment disk formation

The outer segments (OS) of rod and cone photoreceptor cells are specialized sensory cilia that contain hundreds of opsin-loaded stacked membrane disks that enable phototransduction. The biogenesis of these disks is initiated at the OS base, but the driving force has been debated. Here, we studied the function of the protein encoded by the photoreceptor-specific gene C2orf71, which is mutated in inherited retinal dystrophy (RP54). We demonstrate that C2orf71/PCARE (photoreceptor cilium actin regulator) can interact with the Arp2/3 complex activator WASF3, and efficiently recruits it to the primary cilium. Ectopic coexpression of PCARE and WASF3 in ciliated cells results in the remarkable expansion of the ciliary tip. This process was disrupted by small interfering RNA (siRNA)-based down-regulation of an actin regulator, by pharmacological inhibition of actin polymerization, and by the expression of PCARE harboring a retinal dystrophy-associated missense mutation. Using human retinal organoids and mouse retina, we observed that a similar actin dynamics-driven process is operational at the base of the photoreceptor OS where the PCARE module and actin colocalize, but which is abrogated in Pcare-/- mice. The observation that several proteins involved in retinal ciliopathies are translocated to these expansions renders it a potential common denominator in the pathomechanisms of these hereditary disorders. Together, our work suggests that PCARE is an actin-associated protein that interacts with WASF3 to regulate the actin-driven expansion of the ciliary membrane at the initiation of new outer segment disk formation.

Rhodopsin: A Potential Biomarker for Neurodegenerative Diseases.

Retinal alterations have recently been associated with numerous neurodegenerative diseases. Rhodopsin is a G-protein coupled receptor found in the rod cells of the retina. As a biomarker associated with retinal thinning and degeneration, it bears potential in the early detection and monitoring of several neurodegenerative diseases. In this review article, we summarize the findings of correlations between rhodopsin and several neurodegenerative disorders as well as the potential of a novel technique, cSLO, in the quantification of rhodopsin.

Advances in researches of intrinsically photosensitive retinal ganglion cells

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are atypical photoreceptors that are different from classical cone and rod cells. The primary role of ipRGCs is to signal light for largely subconscious, non-image vision such as photoentrainment of circadian rhythm and pupillary light reflex. Recent researches have revealed additional roles for ipRGCs in communication with synapses around, conscious vision reception and pathogenesis of some diseases. Here we review the research advances of morphology, functions and clinical applications of ipRGCs. (Chin J Ophthalmol, 2020, 56: 308-312).

A Bioinspired Wireless Epidermal Photoreceptor for Artificial Skin Vision

AbstractSkin vision can be found in many invertebrates, such as earthworms, jellyfish, and octopuses using light‐sensitive rod cells in the skin. It enables optical perception and colorimetric responses, providing intriguing capabilities that human skin does not have. A bioinspired wireless, battery‐free, artificial skin vision (ASV) device consisting of flexible optical and optoelectronic components which essentially mimic the hierarchical structures and biological functions of rod cells in a skin‐like configuration for light sensing and signal processing is developed. The ASV device can collect sweat with integrated microfluidic channels and allow real‐time measurement of on‐skin fluids by monitoring the intrinsic optical properties via a customizable microprism light filter. The device also shows sensitive colorimetric responses to input stimulus at chosen detection wavelengths and demonstrates a capacity for in situ quantitative analysis of biomarkers in sweat through alternative colorimetric light filters. Multiple ASVs together create a body area network with a collection of wireless sensors that can work in parallel to acquire multidimensional human physiological signals and predict fitness variations using a specified deep learning neural network. The system has potential applications in biomimetic engineering, physiological monitoring, and intelligent personalized diagnostics.