Rod Responses Research Articles

Fractional Burgers wave equation on a finite domain

Dynamic response of the one-dimensional viscoelastic rod of finite length, that has one end fixed and the other subject to prescribed either displacement or stress, is analyzed by the analytical means of Laplace transform, yielding the displacement and stress of an arbitrary rod’s point as a convolution of the boundary forcing and solution kernel. Thermodynamically consistent Burgers models are adopted as the constitutive equations describing mechanical properties of the rod. Short-time asymptotics implies the finite wave propagation speed in the case of the second class models, contrary to the case of the first class models. Moreover, Burgers model of the first class yield quite classical shapes of displacement and stress time profiles resulting from the boundary forcing assumed as the Heaviside function, while model of the second class yield responses that resemble to the sequence of excitation and relaxation processes.

Ocular Characteristics of Patients with Leber Congenital Amaurosis 6 Caused by Pathogenic RPGRIP1 Gene Variation in a Chinese Cohort.

Purpose To delineate the clinical and genetic characteristics of Chinese patients with RPGRIP1-associated Leber congenital amaurosis 6 (LCA6). Methods After screening 352 unrelated families with clinically diagnosed RP, five LCA6 patients with RPGRIP1 variations from unrelated Chinese families were identified. Full ophthalmology examinations, including decimal best-corrected visual acuity (BCVA), fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ffERG), multifocal electroretinography (mfERG), perimetry, and flash visual evoked potential (FVEP), were performed. Target next-generation sequencing (NGS) and Sanger sequencing were performed for the five patients to identify and to validate candidate disease-causing variants. Results Five patients were molecularly diagnosed as the LCA6 associated with RPGRIP1 variation, with typical clinical characteristics including congenital night blindness, nystagmus, and visual defect, at an early age. Interestingly, LCA6 exhibited extensive clinical heterogeneity and the changes in the morphology and function were not completely consistent in the five LCA6 patients. Case 1 showed extensive inferior-nasal retinal atrophy with a corresponding area of hypofluorescence in fundus autofluorescence, and the fundus photograph was nearly normal in cases 2 and 3. The ERG results displayed a moderately reduced rod-system response in cases 1 and 2 and a significant reduced rod-system response in case 3. Both case 4 and case 5 showed mottled pigmentation in fundi and an unrecordable rod and cone-system response in ERG. Moreover, we identified eight compound variants and one homozygous variant in the five patients with RPGRIP1. Conclusions This is the largest report focused on the clinical electrophysiological features of patients with associated LCA6 caused by the variation in the RPGRIP1 gene in the Chinese population with an enriched phenotypic and genotypic background of LCA6 to improve future gene therapies.

Scale-dependent torsional vibration response of non-circular nanoscale auxetic rods

In the current paper, analysis of torsional vibration behavior of non-circular nanorods made of auxetic honeycomb material is investigated for the first time. The triangular and elliptical cross-sections are selected to be analyzed. Moreover, one of the distinct properties of auxetic honeycomb materials is that they possess a negative Poisson’s ratio, which can be effective on the design and analysis of structures. In order to capture a small size or scale effect, the constitutive relation of nanorods is modified based on Eringen’s nonlocal elasticity theory (ENET). Hamilton’s principle is employed to obtain the kinematic relation of nanoscale rods. The nonlocal derived governing equations of non-circular auxetic nanorods are solved by utilizing an analytical method with respect to different boundary conditions. In order to verify the correctness of obtained outcomes, the results are compared to previous investigations, and good agreement can be observable. The influences of various parameters such as both Clamped–Clamped (C–C) and Clamped-Free (C-F) boundary conditions, nonlocal parameters, inclined angles, and geometrical ratios are explored and illustrated in the framework of several figures, which can be seen in detail.

A novel exome probe set captures phototransduction genes across birds (Aves) enabling efficient analysis of vision evolution.

The diversity of avian visual phenotypes provides a framework for studying mechanisms of trait diversification generally, and the evolution of vertebrate vision, specifically. Previous research has focused on opsins, but to fully understand visual adaptation, we must study the complete phototransduction cascade (PTC). Here, we developed a probe set that captures exonic regions of 46 genes representing the PTC and other light responses. For a subset of species, we directly compared gene capture between our probe set and low-coverage whole genome sequencing (WGS), and we discuss considerations for choosing between these methods. Finally, we developed a unique strategy to avoid chimeric assembly by using "decoy" reference sequences. We successfully captured an average of 64% of our targeted exome in 46 species across 14 orders using the probe set and had similar recovery using the WGS data. Compared to WGS or transcriptomes, our probe set: (1) reduces sequencing requirements by efficiently capturing vision genes, (2) employs a simpler bioinformatic pipeline by limiting required assembly and negating annotation, and (3) eliminates the need for fresh tissues, enabling researchers to leverage existing museum collections. We then utilized our vision exome data to identify positively selected genes in two evolutionary scenarios-evolution of night vision in nocturnal birds and evolution of high-speed vision specific to manakins (Pipridae). We found parallel positive selection of SLC24A1 in both scenarios, implicating the alteration of rod response kinetics, which could improve color discrimination in dim light conditions and/or facilitate higher temporal resolution.

Differential impact of Kv8.2 loss on rod and cone signaling and degeneration.

Heteromeric Kv2.1/Kv8.2 channels are voltage-gated potassium channels localized to the photoreceptor inner segment. They carry IKx, which is largely responsible for setting the photoreceptor resting membrane potential. Mutations in Kv8.2 result in childhood-onset cone dystrophy with supernormal rod response (CDSRR). We generated a Kv8.2 knockout (KO) mouse and examined retinal signaling and photoreceptor degeneration to gain deeper insight into the complex phenotypes of this disease. Using electroretinograms, we show that there were delayed or reduced signaling from rods depending on the intensity of the light stimulus, consistent with reduced capacity for light-evoked changes in membrane potential. The delayed response was not seen ex vivo where extracellular potassium levels were controlled by the perfusion buffer, so we propose the in vivo alteration is influenced by genotype-associated ionic imbalance. We observed mild retinal degeneration. Signaling from cones was reduced but there was no loss of cone density. Loss of Kv8.2 altered responses to flickering light with responses attenuated at high frequencies and altered in shape at low frequencies. The Kv8.2 KO line on an all-cone retina background had reduced cone-driven ERG b wave amplitudes and underwent degeneration. Altogether, we provide insight into how a deficit in the dark current affects the health and function of photoreceptors.

Theoretical and Experimental Studies on Pyroshock Attenuation via Periodic Rods

Pyrotechnic releasing devices have been widely used in aerospace missions to separate subsystems from spacecraft. High-frequency transient pyroshock induced by pyrotechnic release devices may cause severe damage to electronic devices and involved systems. To mitigate the pyroshock, phononic crystals, as new artificial constructions with novel properties, are introduced for the first time. In the present study, the pyroshock propagation analysis in periodic composite rods consisting of two different materials is conducted both theoretically and experimentally by considering various geometry parameters. The band gaps, attenuation level, and dynamic responses of periodic rods are investigated by the differential quadrature method, and the simulation results are validated by finite element analysis. Using the established theoretical model and laser-generated shock experimental setups, the effect of geometry on wave propagation behaviors, dynamic responses, shock response spectrums, and pyroshock attenuation in periodic rods are investigated. The experimental and numerical results are in good agreement, demonstrating that effective shock attenuation may be achieved through periodic rods. The corresponding attenuation bands, attenuation trends, and turning points of shock response spectrums can be controlled by designing the geometry of periodic rods. The pyroshock attenuation effects in periodic rods can be predicted quantitatively by wave propagation analysis.

Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family.

BackgroundCone dystrophy with supernormal rod response (CDSRR) is an autosomal recessive retinal disorder characterized by myopia, dyschromatopsia, nyctalopia, photophobia, and nystagmus. CDSRR is caused by mutations in KCNV2, the gene encoding for an electrically silent Kv subunit (Kvs) named Kv8.2.MethodsA Chinese CDSRR family was recruited. Complete ophthalmology clinical examinations were performed to clarify the phenotype. Genetic examination was underwent using whole exome sequencing (WES). In addition, a candidate gene was validated by Sanger sequencing. Expression analysis in vitro including immunoblotting, quantitative real‐time PCR (qRT‐PCR), and co‐immunoprecipitation experiments was performed to investigate the pathogenic mechanism of the identified gene variants.ResultsWES identified two KCNV2 heterozygous mutations from the proband. Sanger sequencing validated that the patient's parents had, respectively, carried those two mutations. Further in vitro functional experiments indicated that the mutated alleles had led the Kv8.2 proteins to fail in expressing and interacting with the Kv2.1 protein, respectively.ConclusionsThis study expanded the KCNV2 mutation spectrum. It can also be deduced that CDSRR has a broad heterogeneity. It is further confirmed that the inability expression of Kv8.2 proteins and the failure of Kv8.2 proteins to interact with Kv2.1 may have accounted for the etiology of CDSRR based on previous studies and this study.

EPR dosimetric studies on strontium sulfate rods for possible use in radiotherapy

Radiation-induced radicals in the crystals of strontium sulfate (SS) as rod dosimeters were studied using an electron paramagnetic resonance (EPR) spectrometer. Dosimetric studies were performed in the dose range of 0.5 to 25 Gy for the dosimeters to investigate their potential applications in radiotherapy (60Co γ-rays and high megavoltage X-ray with 6 and 15 MV). Additionally, the response of these dosimeters was compared to the response of alanine pellet dosimeters at the three-beam qualities. Irradiation of SS dosimeters produces five EPR signals, and their intensity increases linearly with increasing absorbed doses from 0.5 to 25 Gy. A peak of a splitting g-factor (g) = 2.01039 was selected for the present evaluations as it has a higher intensity. The change in response of SS rod dosimeters after irradiation does not exceed ±2% over six months, exhibiting good stability. The response of SS dosimeters increases with increasing the incident beam energy from 60Co gamma rays to 16 MV X-ray beam. For alanine dosimeters, a non-significant change is observed under these beam qualities. The response of SS dosimeter at 6 and 15 MV relative to a60Co beam quality increases by about 3.8% and 14.1%, respectively.Moreover, the response of the SS dosimeters increases 2.24% with increasing the dose rate from 100 to 400 cGy/min, while for the alanine dosimeters, the increase in response is less than 0.49%. Environmental factors (relative humidity levels of 0–76% and temperature degrees of 15–30 °C) have a slight impact on the response of SS rods during irradiation. The overall uncertainty of dose monitoring was reported to be ±4.02% (2σ, 95% confidence levels).

Dietary Supplementation of Antioxidant Compounds Prevents Light-Induced Retinal Damage in a Rat Model.

Light-induced retinal damage (LD) is characterized by the accumulation of reactive oxygen species leading to oxidative stress and photoreceptor cell death. The use of natural antioxidants has emerged as promising approach for the prevention of LD. Among them, lutein and cyanidin-3-glucoside (C3G) have been shown to be particularly effective due to their antioxidant and anti-inflammatory activity. However, less is known about the possible efficacy of combining them in a multicomponent mixture. In a rat model of LD, Western blot analysis, immunohistochemistry and electroretinography were used to demonstrate that lutein and C3G in combination or in a multicomponent mixture can prevent oxidative stress, inflammation, gliotic and apoptotic responses thus protecting photoreceptor cells from death with higher efficacy than each component alone. Combined efficacy on dysfunctional electroretinogram was also demonstrated by ameliorated rod and cone photoreceptor responses. These findings suggest the rationale to formulate multicomponent blends which may optimize the partnering compounds bioactivity and bioavailability.

The structure\u2013function correlation analysed by OCT and full field ERG in typical and pericentral subtypes of retinitis pigmentosa

To investigate the structure–function correlation analysed by full-field electroretinography (ffERG) and optical coherence tomography (OCT) in typical and pericentral subtypes of retinitis pigmentosa (RP). A retrospective, cross-sectional, observational study of right eyes was conducted. The primary analysis used ffERG data to compare the RP subtypes. The subgroup analysis was used to correlate the structure, analysed by OCT, and function, determined by ffERG. Linear regressions explored the relationship between best-corrected visual acuity (BCVA) and multiple parameters. A total of 188 eyes were included. Amplitudes of responses of rod, rod-cone, cone, and 30 Hz flicker of typical type were lower than those of pericentral and other types. In the subgroup analysis, 41 and 21 eyes of the typical and pericentral types were studied, respectively. The correlation between the estimated preserved photoreceptor area and all ffERG amplitude parameters were significant in the typical type, but not in pericentral type. Old age, decreased intact ellipsoid zone length, typical type, and thin central retinal thickness were negatively correlated with BCVA. Typical type RP developed more extensive degeneration and poorer BCVA compared to others. Strong structure–function correlation was found in typical type while not in pericentral type. OCT may be a useful tool for monitoring RP status in typical type, providing useful parameters for the prediction of BCVA.

Dynamic response of hollow sandwich cement rod of 110 Kv transmission line

Taking a 110 kV transmission line as the research object, a refined finite element model of three pole two line transmission tower line system is established.Considering collision and contact between a dropped wire and ground, nonlinear dynamic analyses of the system with different break points and different numbers of broken wires were performed. The results showed that the break point location has little effects on the impact action of broken wire; the tension decay coefficient of the broken wire decreases with increase in the height of the hanging point position, while that of the unbroken wire decreases first and then increases with increase in the height of the hanging point position. The initial pretension, wind direction angle and span of the cable are selected for parameter analysis. The influence of these parameters on the nonlinear dynamic stability critical load of the hollow mezzanine concrete pole line system is investigated.

Biocompatibility of polyvinyl alcohol/trisodium trimetaphosphate as vitreous substitute in experimental vitrectomy model in rabbits.

Synthetic hydrogels have been proposed as vitreous substitutes recently. This study aims to evaluate the biocompatibility of polyvinyl alcohol (PVA) crosslinked with trisodium trimetaphosphate (SMTP) hydrogel in rabbit vitrectomized eyes. Seven animals were submitted to pars plana vitrectomy and the vitreous was replaced by PVA/SMTP hydrogel. Optical coherence tomography, fluorescein angiogram, clinical, and electrophysiological (ERG) examinations were analyzed at baseline, on postoperative days 7 and 30. The fellow eye was used as the control group. Hydrogel opacification was observed and ERG recordings were reduced in the hydrogel group in rod response, b-wave cone response and flicker. A histological analysis showed retinal disorganization, presence of multinucleated cells, and intraretinal hydrogel particles. The PVA/SMTP hydrogel showed poor biocompatibility. Novel biomaterials compounds should be analyzed in vivo.

The role of voltage-gated ion channels in visual function and disease in mammalian photoreceptors.

Light activation of the classical light-sensing retinal neurons, the photoreceptors, results in a graded change in membrane potential that ultimately leads to a reduction in neurotransmitter release to the post-synaptic retinal neurons. Photoreceptors show striking powers of adaptation, and for visual processing to function optimally, they must adjust their gain to remain responsive to different levels of ambient light intensity. The presence of a tightly controlled balance of inward and outward currents modulated by several different types of ion channels is what gives photoreceptors their remarkably dynamic operating range. Part of the resetting and modulation of this operating range is controlled by potassium and calcium voltage-gated channels, which are involved in setting the dark resting potential and synapse signal processing, respectively. Their essential contribution to visual processing is further confirmed in patients suffering from cone dystrophy with supernormal rod response (CDSRR) and congenital stationary night blindness type 2 (CSNB2), both conditions that lead to irreversible vision loss. This review will discuss these two types of voltage-gated ion channels present in photoreceptors, focussing on their structure and physiology, and their role in visual processing. It will also discuss the use and benefits of knockout mouse models to further study the function of these channels and what routes to potential treatments could be applied for CDSRR and CSNB2.

Correlation Between Electroretinogram and Visual Prognosis in Metallic Intraocular Foreign Body Injury.

Purpose: This study aims to investigate the correlation between electroretinogram (ERG) and visual outcome in eyes with metallic intraocular foreign body (IOFB) injury.Methods: Cases with metallic IOFB injuries with preoperative ERG from January 2008 to May 2020 were reviewed retrospectively. Five ERG responses were recorded, including rod response, maximal response, oscillatory potentials, cone response, and 30-Hz flicker. The results were compared between the affected and the contralateral eyes. All patients received surgery to remove IOFBs. The correlation between amplitudes, implicit times, and grades of ERG with final best-corrected visual acuity (BCVA) was analyzed.Results: A total of 33 eyes of 33 patients were included. The eyes with IOFB had generally delayed implicit time and reduced amplitude in all waves. The maximum change was found in oscillatory potentials S3 and N1 (0.42 ± 0.42 and 1.95 ± 1.97 of the fellow eyes, respectively, p < 0.05). All amplitudes were negatively correlated with the final BCVA (rs: −0.676 to −0.459, all p < 0.05). In contrast, all implicit times were positively correlated with final BCVA, although, some of them were not statistically significant (rs: 0.035 to 0.687). Among them, oscillatory potential P3 has the highest correlation coefficient (rs = 0.687, p < 0.001). All grades of ERG waves were statistically correlated with the final BCVA (rs: −0.596 to −0.664, all p < 0.001).Conclusions: ERG can be used to assess visual outcome in metallic IOFB injury after surgery. Oscillatory potentials provided the most significant responses.

Nonlinear stochastic vibration of a variable cross-section rod with a fractional derivative element

The article deals with the problem of computing efficiently the nonlinear response of a rod involving a fractional constitutive model, and exposed to random excitation. The constitutive model is a three-parameter model comprising an instant elasticity modulus, a prolonged elasticity modulus, and a relaxation parameter. The nonlinear term is a linear-plus-cubic force of the Winkler kind. The resulting nonlinear fractional partial differential equation governing the rod displacement has no known exact solution. Thus, the article proposes an approximate analytical solution by relying on the statistical linearization technique. Further, it develops a Boundary Element Method (BEM)-based approach to estimate numerically the rod response statistics. The statistical linearization solution is obtained by representing the rod displacement as the superposition of linear modes of vibration having time-dependent coefficients. In this context, it is shown that the equation governing the time variation of the mode coefficients is a nonlinear fractional ordinary differential equation, whose solution is computed by a surrogate linear system identified by minimizing the response error between the linear system and the nonlinear one in a mean square sense. Relevant Monte Carlo studies pertaining to rods with fixed-fixed, and fixed-free ends show that the proposed analytical solution is in a good agreement with data obtained by the numerical (BEM) approach.

Analysis of waveform and amplitude of mouse rod and cone flash responses.

Most vertebrate eyes have rod and cone photoreceptors, which use a signal transduction pathway consisting of many biological processes to transform light into an electrical response. We dissect and quantify the contribution of each of these processes to the photoreceptor light response by using a novel method of analysis that provides an analytical solution for the entire time course of the dim-flash light response. We find that the shape of the light response is exclusively controlled by deactivation parameters. Activation parameters scale this shape and alter the response amplitude. We show that the rising phase of the response depends on Ca2+ feedback, and we identify the deactivation parameters that control the recovery phase of the response. We devise new methods to extract values for deactivation and activation parameters from a separate analysis of response shape and response amplitude. Vertebrate eyes have rod and cone photoreceptors, which use a complex transduction pathway comprising many biological processes to transform the absorption of light into an electrical response. A fundamental question in sensory transduction is how these processes contribute to the response. To study this question, we use a well-accepted phototransduction model, which we analyse with a novel method based on the log transform of the current. We derive an analytical solution that describes the entire time course of the photoreceptor response to dim flashes of light. We use this solution to dissect and quantify the contribution of each process to the response. We find that the entire dim-flash response is proportional to the flash intensity. By normalizing responses to unit amplitude, we define a waveform that is independent of the light intensity and characterizes the invariant shape of dim-flash responses. We show that this waveform is exclusively determined by deactivation rates; activation rates only scale the waveform and affect the amplitude. This analysis corrects a previous assumption that the rising phase is determined entirely by activation rates. We further show that the rising phase depends on Ca2+ feedback to the cyclase, contrary to current belief. We identify the deactivation rates that control the recovery phase of the response, and we devise new methods to extract activation and deactivation rates from an analysis of response shape and response amplitude. In summary, we provide a comprehensive understanding of how the various transduction processes produce the cellular response.

Novel variants in GUCY2D causing retinopathy and the genotype-phenotype correlation

Leber congenital amaurosis (LCA) is the most severe form of retinopathy and cone/cone-rod dystrophy (CORD) is a common form of inherited retinopathy. Variants in GUCY2D constitute the most common cause of LCA and autosomal dominant CORD (ADCORD). The purpose of this study was to reveal novel variants and document associated phenotypes of patients with GUCY2D-associated retinopathy. Fifty-two potentially pathogenic variants (PPVs), including 12 novel ones (p.Gly144_Ala164del, p.Trp154Glyfs*12, p.Leu186Pro, p.Ala207Pro, p.Ala229Asp, p.Ala353Glu, p.Trp372*, p.Arg528*, p.Arg660Pro, p.Ile682Thr, p.Trp788Cys, and c.1026 + 171_*486del), were identified in 16 families with ADCORD and 34 families with autosomal recessive LCA (ARLCA). The novel variant c.1026 + 171_*486del is a large-scale (16.3 kb) deletion involving exons 4–20 of GUCY2D, and was identified in an ARLCA family in heterozygous status mimicking a homozygous p.Trp788Cys variant. Among the detected 52 PPVs, 32 (61.5%) were missense, seven (13.5%) were splicing, six (11.5%) were nonsense, four (7.7%) were inframe indel, and three (5.8%) were frameshift deletion. The median age of examination in 27 patients with ADCORD was 21.0 years (ranges 3–54) with a median visual acuity (VA) of 0.10 (ranges 0.02–0.90). There were 48.0% of patients with macular atrophy, 86.4% with severe reduced or extinguished cone responses, 77.3% with normal or mildly reduced rod responses, and 60.9% with high myopia. Visual impairment, macular dystrophy, and cone dysfunction deteriorated with age. The median age of examination in 34 patients with ARLCA was 1.1 years (ranges 0.3–25). There were 55.9% of patients with roving nystagmus, 68.2% with VA of worse than hand motion, 59.4% with almost normal fundus, 90.6% with extinguished rod and cone responses, and 50.0% with high hyperopia. In conclusions, twelve novel PPVs in GUCY2D (including a novel large-scale deletion) were identified. Most (32/52, 61.5%) of causative GUCY2D variants were missense. Progressive development of macular atrophy, cone dysfunction, visual impairment, and myopia are four major characteristics of GUCY2D-associated ADCORD. Normal fundus, roving nystagmus, and hypermetropia in early age are common findings specific to GUCY2D-associated ARLCA. The obtained data in this study will be of value in counselling patients and designing future therapeutic approaches.

Advanced Retinal Imaging and Ocular Parameters of the Rhesus Macaque Eye.

PurposeTo determine the range of normal ocular biometry and perform advanced retinal imaging and functional assessment of the rhesus macaque eye.MethodsWe performed ocular phenotyping on rhesus macaques at the California National Primate Research Center. This process consisted of anterior and posterior segment eye examination by ophthalmologists, advanced retinal imaging, and functional retinal electrophysiology.ResultsFull eye examinations were performed on 142 animals, consisting of pupillary light reflex, tonometry, external examination and photography, anterior slit lamp examination, and posterior segment examination by indirect ophthalmoscopy. Ages of the rhesus macaques ranged from 0.7 to 29 years (mean, 16.4 ± 7.5 years). Anterior segment measurements such as intraocular pressure (n = 142), corneal thickness (n = 84), lens thickness (n = 114), and axial length (n = 114) were acquired. Advanced retinal imaging in the form of fundus photography (n = 78), optical coherence tomography (n = 60), and quantitative autofluorescence (n = 44) was obtained. Electroretinography (n = 75) was used to assay retinal function. Quantitative analyses of the macular structure, retinal layer segmentation, and rod and cone photoreceptor electrical responses are reported. Quantitative assessments were made and variations between sexes were analyzed to compare with established sex changes in human eyes.ConclusionsThe rhesus macaque has an ocular structure and function very similar to that of the human eye. In particular macular structure and retinal function is very similar to humans, making this species particularly useful for the study of macular biology and development of therapies for cone photoreceptor disorders.Translational RelevanceRhesus macaques are an ideal model for future vision science studies of human eye diseases.

Molecular, Cellular and Functional Changes in the Retinas of Young Adult Mice Lacking the Voltage-Gated K+ Channel Subunits Kv8.2 and K2.1.

Cone Dystrophy with Supernormal Rod Response (CDSRR) is a rare autosomal recessive disorder leading to severe visual impairment in humans, but little is known about its unique pathophysiology. We have previously shown that CDSRR is caused by mutations in the KCNV2 (Potassium Voltage-Gated Channel Modifier Subfamily V Member 2) gene encoding the Kv8.2 subunit, a modulatory subunit of voltage-gated potassium (Kv) channels. In a recent study, we validated a novel mouse model of Kv8.2 deficiency at a late stage of the disease and showed that it replicates the human electroretinogram (ERG) phenotype. In this current study, we focused our investigation on young adult retinas to look for early markers of disease and evaluate their effect on retinal morphology, electrophysiology and immune response in both the Kv8.2 knockout (KO) mouse and in the Kv2.1 KO mouse, the obligate partner of Kv8.2 in functional retinal Kv channels. By evaluating the severity of retinal dystrophy in these KO models, we demonstrated that retinas of Kv KO mice have significantly higher apoptotic cells, a thinner outer nuclear cell layer and increased activated microglia cells in the subretinal space. Our results indicate that in the murine retina, the loss of Kv8.2 subunits contributes to early cellular and physiological changes leading to retinal dysfunction. These results could have potential implications in the early management of CDSRR despite its relatively nonprogressive nature in humans.

Oguchi's disease: two cases and literature review.

Oguchi's disease is a rare form of congenital stationary night blindness, associated with light-dependent golden fundus discoloration. In this report, we describe two cases of Oguchi's disease, both of which had two characteristic features: congenital stationary night blindness and fundoscopic manifestation of the Mizuo–Nakamura phenomenon. In both patients, fundus examination revealed a metallic sheen throughout the retina, which disappeared after 2.5 hours of dark adaptation, suggestive of the Mizuo–Nakamura phenomenon. The characteristic electroretinogram (ERG) changes (i.e., un-recordable rod response and reductions of maximal response, oscillatory potentials, and flicker response) in these patients confirmed the clinical diagnosis of Oguchi's disease. Furthermore, we discuss the results of our literature search for evidence concerning the diagnosis and pathogenesis of this rare disease. Further studies regarding the genes involved in phototransduction and light adaptation are needed to determine the pathogenesis of this rare disease.