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retina - Top 30 Publications

A model for investigating developmental eye repair in Xenopus laevis.

Vertebrate eye development is complex and requires early interactions between neuroectoderm and surface ectoderm during embryogenesis. In the African clawed frog, Xenopus laevis, individual eye tissues such as the retina and lens can undergo regeneration. However, it has been reported that removal of either the specified eye field at the neurula stage or the eye during tadpole stage does not induce replacement. Here we describe a model for investigating Xenopus developmental eye repair. We found that tailbud embryos can readily regrow eyes after surgical removal of over 83% of the specified eye and lens tissues. The regrown eye reached a comparable size to the contralateral control by 5 days and overall animal development was normal. It contained the expected complement of eye cell types (including the pigmented epithelium, retina and lens), and connected to the brain. Our data also demonstrate that apoptosis, an early mechanism that regulates appendage regeneration, is also required for eye regrowth. Treatment with apoptosis inhibitors (M50054 or NS3694) blocked eye regrowth by inhibiting capase activation. Together, our findings indicate that frog embryos can undergo successful eye repair after considerable tissue loss and reveals a required role for apoptosis in this process. Furthermore, this Xenopus model allows for rapid comparisons of productive eye repair and developmental pathways. It can also facilitate the molecular dissection of signaling mechanisms necessary for initiating repair.



Clinical Applicability of Deep Learning System in Detecting Tuberculosis with Chest Radiography.

The Human Eye Proteome Project: Updates on an Emerging Proteome.

The human eye is a complex organ consisting of multiple compartments with unique and specialized properties that reflect their varied functions. Although there have been advancements in ocular imaging and therapeutics over the past decade, the pathogenesis of many common eye diseases remains poorly understood. Proteomics is an invaluable tool to gain insight into pathogenesis, diagnosis, and treatment of eye diseases. By 2013, when the Human Eye Proteome Project (also known as the EyeOme) was founded, there were 4,842 non-redundant proteins identified in the human eye. Twenty-three recent papers on the human eye proteome were identified in PubMed searches. These papers were used to compile an updated resource of 9,782 non-redundant proteins in the human eye. This updated catalogue sheds light on the molecular make-up of previously undescribed proteomes within the human eye, including optic nerve, sclera, iris, and ciliary body, while adding additional proteins to previously characterized proteomes such as aqueous humor, lens, vitreous, retina, and retinal pigment epithelium/choroid. Although considerable advances have been made to characterize the complete proteome of the human eye, additional high-quality data is needed to confirm and quantify previously discovered eye proteins in both health and disease. This article is protected by copyright. All rights reserved.

670nm light treatment following retinal injury modulates Müller cell gliosis: Evidence from in vivo and in vitro stress models.

Photobiomodulation (PBM) with 670 nm light has been shown to accelerate wound healing in soft tissue injuries, and also to protect neuronal tissues. However, little data exist on its effects on the non-neuronal components of the retina, such as Müller cells (MCs), which are the principal macroglia of the retina that play a role in maintaining retinal homeostasis. The aim of this study was to explore the effects of 670 nm light on activated MCs using in vivo and in vitro stress models. Adult Sprague-Dawley rats were exposed to photo-oxidative damage (PD) for 24 h and treated with 670 nm light at 0, 3 and 14 days after PD. Tissue was collected at 30 days post-PD for analysis. Using the in vitro scratch model with a human MC line (MIO-M1), area coverage and cellular stress were analysed following treatment with 670 nm light. We showed that early treatment with 670 nm light after PD reduced MC activation, lowering the retinal expression of GFAP and FGF-2. 670 nm light treatment mitigated the production of MC-related pro-inflammatory cytokines (including IL-1β), and reduced microglia/macrophage (MG/MΦ) recruitment into the outer retina following PD. This subsequently decreased photoreceptor loss, slowing the progression of retinal degeneration. In vitro, we showed that 670 nm light directly modulated MC activation, reducing rates of area coverage by suppressing cellular proliferation and spreading. This study indicates that 670 nm light treatment post-injury may have therapeutic benefit when administered shortly after retinal damage, and could be useful for retinal degenerations where MC gliosis is a feature of disease progression.

Results of a community-based screening programme for diabetic retinopathy and childhood blindness in district Hyderabad, Pakistan.

To present the results of a community-based screening programme for diabetes, diabetic retinopathy (DR) and childhood blindness (CB) in District Hyderabad, Pakistan.

Transcorneal electrical stimulation for the treatment of retinitis pigmentosa: results from the TESOLAUK trial.

To explore the impact of weekly transcorneal electrical stimulation (TES) over a 6-month period as a treatment for retinitis pigmentosa (RP).

Diabetic retinopathy screening and treatment in Myanmar: a pilot study.

The goals of this pilot study were (a) to demonstrate the feasibility of identifying patients with vision-threatening diabetic retinopathy (DR) in a provincial area of Myanmar and treating them with portable lasers and (b) to gather data specific to Myanmar to help design larger cross-sectional studies of DR prevalence in Myanmar.

Therapeutic potential of omega-3 fatty acids supplementation in a mouse model of dry macular degeneration.

To evaluate the therapeutic effects of omega-3 (ω-3) and omega-6 (ω-6) fatty acids in the CCL2-/- model of dry age-related macular degeneration (AMD). The blood level of eicosapentaenoic acid (EPA) and arachidonic acid (AA) served to adjust the treatment dosage (AA/EPA=1-1.5).

Pre-eclampsia and the risk of retinopathy of prematurity in preterm infants with birth weight <1500 g and/or <31 weeks' gestation.

To evaluate the relationship between pre-eclampsia and development of retinopathy of prematurity (ROP) in infants with birth weight of <1500 g and/or gestation <31 weeks.

Retinal embolic events: frequency and impact following transcatheter aortic valve implantation (TAVI) for aortic stenosis.

Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe symptomatic aortic stenosis. It has a cerebrovascular accident rate of about 5% but the effect on retinal embolic events has not been previously reported. This study investigated the occurrence of retinal emboli following TAVI.

The Effect of Vitrectomy Infusion Solutions on Postoperative Electroretinography and Retina Histology.

A prospective, randomised, masked study comparing three different intraocular infusion solutions used during vitrectomy on postoperative electroretinography (ERG) and retinal histology of rabbit eyes.

The Regulation of Notch Signaling in Retinal Development and Regeneration.

Notch signaling is an important component of retinal progenitor cell maintenance and MG specification during development, and its manipulation may be critical for allowing MG to re-enter the cell cycle and regenerate neurons in adults. In mammals, MG respond to retinal injury by undergoing a gliotic response rather than a regenerative one. Understanding the complexities of Notch signaling may allow for strategies that enhance regeneration over gliosis.

Early Microglia Activation Precedes Photoreceptor Degeneration in a Mouse Model of CNGB1-Linked Retinitis Pigmentosa.

Retinitis pigmentosa (RP) denotes a family of inherited blinding eye diseases characterized by progressive degeneration of rod and cone photoreceptors in the retina. In most cases, a rod-specific genetic defect results in early functional loss and degeneration of rods, which is followed by degeneration of cones and loss of daylight vision at later stages. Microglial cells, the immune cells of the central nervous system, are activated in retinas of RP patients and in several RP mouse models. However, it is still a matter of debate whether activated microglial cells may be responsible for the amplification of the typical degenerative processes. Here, we used Cngb1-/- mice, which represent a slow degenerative mouse model of RP, to investigate the extent of microglia activation in retinal degeneration. With a combination of FACS analysis, immunohistochemistry and gene expression analysis we established that microglia in the Cngb1-/- retina were already activated in an early, predegenerative stage of the disease. The evidence available so far suggests that early retinal microglia activation represents a first step in RP, which might initiate or accelerate photoreceptor degeneration.

Safety study of intravitreal and suprachoroidal Laponite clay in rabbit eyes.

To study the safety and biocompatibility of Laponite clay (LAP) within an intravitreal and suprachoroidal administration in rabbit eyes.

Comparison of chorioretinal layers in rhesus macaques using spectral-domain optical coherence tomography and high-resolution histological sections.

Nonhuman primates are important preclinical models of retinal diseases because they uniquely possess a macula similar to humans. Ocular imaging technologies such as spectral-domain optical coherence tomography (SD-OCT) allow noninvasive, in vivo measurements of chorioretinal layers with near-histological resolution. However, the boundaries are based on differences in reflectivity, and detailed correlations with histological tissue layers have not been explored in rhesus macaques, which are widely used for biomedical research. Here, we compare the macular anatomy and thickness measurements of chorioretinal layers in rhesus macaque eyes using SD-OCT and high-resolution histological sections. Images were obtained from methylmethacrylate-embedded histological sections of 6 healthy adult rhesus macaques, and compared with SD-OCT images from 6 age-matched animals. Thicknesses of chorioretinal layers were measured across the central 3 mm macular region using custom semi-automated or manual software segmentation, and compared between the two modalities. We found that histological sections provide better distinction between the ganglion cell layer (GCL) and inner plexiform layer (IPL) than SD-OCT imaging. The first hyperreflective band between the external limiting membrane (ELM) and retinal pigment epithelium (RPE) appears wider on SD-OCT than the junction between photoreceptor inner and outer segments seen on histology. SD-OCT poorly distinguishes Henle nerve fibers from the outer nuclear layer (ONL), while histology correctly identifies these fibers as part of the outer plexiform layer (OPL). Overall, the GCL, inner nuclear layer (INL), and OPL are significantly thicker on histology, especially at the fovea; while the ONL, choriocapillaris (CC), and outer choroid (OC) are thicker on SD-OCT. Our results show that both SD-OCT and high-resolution histological sections allow reliable measurements of chorioretinal layers in rhesus macaques, with distinct advantages for different sublayers. These findings demonstrate the effects of tissue processing on chorioretinal anatomy, and provide normative values for chorioretinal thickness measurements on SD-OCT for future studies of disease models in these nonhuman primates.

Eliminating Glutamatergic Input onto Horizontal Cells Changes the Dynamic Range and Receptive Field Organization of Mouse Retinal Ganglion Cells.

In the mammalian retina, horizontal cells receive glutamatergic inputs from many rod and cone photoreceptors and return feedback signals to them, thereby changing photoreceptor glutamate release in a light-dependent manner. Horizontal cells also provide feedforward signals to bipolar cells. It is unclear, however, how horizontal cell signals also affect the temporal, spatial and contrast tuning in retinal output neurons, the ganglion cells. To study this, we generated a genetically modified mouse line in which we eliminated the light dependency of feedback by deleting glutamate receptors from mouse horizontal cells. This genetic modification allowed us to investigate the impact of horizontal cells on ganglion cell signaling independent of the actual mode of feedback in the outer retina and without pharmacological manipulation of signal transmission. In control and genetically modified mice (both sexes), we recorded the light responses of transient OFF-α retinal ganglion cells in the intact retina. Excitatory postsynaptic currents were reduced and the cells were tuned to lower temporal frequencies and higher contrasts, presumably because photoreceptor output was attenuated. Moreover, receptive fields of recorded cells showed a significantly altered surround structure. Our data thus suggest that horizontal cells are responsible for adjusting the dynamic range of retinal ganglion cells and, together with amacrine cells, contribute to the center/surround organization of ganglion cell receptive fields in the mouse.SIGNIFICANCE STATEMENTHorizontal cells represent a major neuronal class in the mammalian retina and provide lateral feedback and feedforward signals to photoreceptors and bipolar cells, respectively. The mode of signal transmission remains controversial and, moreover, the contribution of horizontal cells to visual processing is still elusive. To address the question of how horizontal cells affect retinal output signals, we recorded the light responses of transient OFF-α retinal ganglion cells in a newly generated mouse line. In this mouse line, horizontal cell signals were no longer modulated by light. With light response recordings, we show that horizontal cells increase the dynamic range of retinal ganglion cells for contrast and temporal changes and contribute to the center/surround organization of their receptive fields.

Intravitreal bevacizumab for postviral fever retinitis: a novel approach for early resolution of macular oedema.

Severe macular oedema causing marked loss of vision is seen in cases of retinitis developing postviral fever. The use of antivascular endothelial growth factor agents for macular oedema and submacular fluid secondary to viral retinitis has not been studied or well established in the past. We report a case series of two patients of postviral retinitis with severe macular oedema resistant to steroid therapy, treated with intravitreal bevacizumab. The patients showed significant symptomatic improvement in the visual acuity. The retinitis lesions resolved slowly and macular oedema regressed. Bevacizumab appears to be a safe and useful agent to manage macular oedema subsequent to postviral retinitis. An early resolution of macular oedema helps in the preservation of visual acuity which left untreated can cause severe visual loss.

Retinal complications of gout: a case report and review of the literature.

There have been few reported findings of posterior segment complications of gout. While exudative lesions, an increased risk of macular degeneration, and vascular occlusions have been previously reported, to our knowledge, refractile macular lesions have not been reported in a patient with chronic uncontrolled gout.

Crying Retina Sign.

Microfluidics-Based Subretinal Chemical Neuromodulation of Photoreceptor Degenerated Retinas.

Retinal prostheses can restore rudimentary vision in cases of photoreceptor degeneration through electrical stimulation, but face difficulties achieving high spatial resolution because electrical current is an inherently unnatural stimulus. We investigated the therapeutic feasibility of using patterned delivery of the glutamate neurotransmitter, a primary agent of natural synaptic communication of the retina, as a biomimetic chemical alternative to electrical current for neuromodulation of photoreceptor degenerate retina.

Intraocular currents, Bernoulli's principle and non-drainage scleral buckling for rhegmatogenous retinal detachment.

For many years, it is not fully understood how non-drainage scleral buckling surgery brings about spontaneous reattachment of the detached retina when retinal breaks remain open at the end of surgery. Various explanations have been put forward, but none more interesting than the effect of fluid currents associated with eye movements. One such explanation involved the physics of the Bernoulli's principle. Daniel Bernoulli was an eighteenth century Swiss mathematician and he described an equation based on the conservation of energy. The sum of pressure energy, potential energy and kinetic energy remains constant. Bernoulli's equation usually applies to closed system such as the flow of fluid through pipes. When fluid flows through a constriction, the speed of fluid increases, the kinetic energy increases. If there was no change in elevation (potential energy), then the increase in kinetic energy must be accompanied by a decrease in pressure energy. In ophthalmic surgery, the Bernoulli's effect is the basis for venturi pumps that drive vitrectomy and phacoemulsification machines. This essay expounds on how Bernoulli's effect might be relevant to scleral buckling for retinal detachment repair. In the era when vitrectomy is increasing the primary surgical operation for retinal detachment, the pervasive advice is to emphasise the importance of patient adopting head posture and remaining still postoperatively. The exception is non-drainage scleral buckling surgery. Early postoperative mobilisation may be vital to achieve reattachment.Eye advance online publication, 19 January 2018; doi:10.1038/eye.2017.312.

Detection of Silent Type I Choroidal Neovascular Membrane in Chronic Central Serous Chorioretinopathy Using En Face Swept-Source Optical Coherence Tomography Angiography.

To evaluate the efficacy of SS-OCTA in the detection of silent CNV secondary to chronic CSCR compared to that of FFA and SS-OCT.

Tubby-like protein 1 (Tulp1) is a target of microRNA-134 and is down-regulated in experimental epilepsy.

MicroRNAs are important determinants of gene expression via post-transcriptional control of the protein levels of their mRNA targets. MicroRNA-134 (miR-134) has emerged as an important brain-specific microRNA which has been implicated in the control of dendritic spine morphology, neuronal differentiation and apoptosis. Here we show that Tubby-like protein 1 (Tulp1) is a target of miR-134. Tulp1 protein showed a similar cellular distribution pattern in the hippocampus to miR-134 and displayed an inverse expression pattern in the mouse retina. Bioinformatics analyses identified a conserved miR-134 binding site in the 3' untranslated region of both mouse and human Tulp1 and luciferase reporter assays confirmed miR-134 targets Tulp1 in vitro. Induction of prolonged seizures in mice resulted in upregulation of miR-134 and downregulation of protein levels of Tulp1 which were reversed in animals injected with locked nucleic acid-modified antagomirs targeting miR-134. Finally, knockdown of Tulp1 in human neurons caused an increase in vulnerability to excitotoxicity. These data identify Tulp1/TULP1 as a novel target of miR-134, which may contribute to underlying pathomechanisms in epilepsy.

Temporal diabetes-induced biochemical changes in distinctive layers of mouse retina.

To discover the mechanisms underlying the progression of diabetic retinopathy (DR), a more comprehensive understanding of the biomolecular processes in individual retinal cells subjected to hyperglycemia is required. Despite extensive studies, the changes in the biochemistry of retinal layers during the development of DR are not well known. In this study, we aimed to determine a more detailed understanding of the natural history of DR in Akita/+ (type 1 diabetes model) male mice with different duration of diabetes. Employing label-free spatially resolved Fourier transform infrared (FT-IR) chemical imaging engaged with multivariate analysis enabled us to identify temporal-dependent reproducible biomarkers of the individual retinal layers from mice with 6 weeks,12 weeks, 6 months, and 10 months of age. We report, for the first time, the nature of the biochemical alterations over time in the biochemistry of distinctive retinal layers namely photoreceptor retinal layer (PRL), inner nuclear layer (INL), and plexiform layers (OPL, IPL). Moreover, we present the molecular factors associated with the changes in the protein structure and cellular lipids of retinal layers induced by different duration of diabetes. Our paradigm provides a new conceptual framework for a better understanding of the temporal cellular changes underlying the progression of DR.

Rapid updating of spatial working memory across saccades.

Each time we make an eye movement, positions of objects on the retina change. In order to keep track of relevant objects their positions have to be updated. The situation becomes even more complex if the object is no longer present in the world and has to be held in memory. In the present study, we used saccadic curvature to investigate the time-course of updating a memorized location across saccades. Previous studies have shown that a memorized location competes with a saccade target for selection on the oculomotor map, which leads to saccades curving away from it. In our study participants performed a sequence of two saccades while keeping a location in memory. The trajectory of the second saccade was used to measure when the memorized location was updated after the first saccade. The results showed that the memorized location was rapidly updated with the eyes curving away from its spatial coordinates within 130 ms after the first eye movement. The time-course of updating was comparable to the updating of an exogenously attended location, and depended on how well the location was memorized.

Learning to make external sensory stimulus predictions using internal correlations in populations of neurons.

To compensate for sensory processing delays, the visual system must make predictions to ensure timely and appropriate behaviors. Recent work has found predictive information about the stimulus in neural populations early in vision processing, starting in the retina. However, to utilize this information, cells downstream must be able to read out the predictive information from the spiking activity of retinal ganglion cells. Here we investigate whether a downstream cell could learn efficient encoding of predictive information in its inputs from the correlations in the inputs themselves, in the absence of other instructive signals. We simulate learning driven by spiking activity recorded in salamander retina. We model a downstream cell as a binary neuron receiving a small group of weighted inputs and quantify the predictive information between activity in the binary neuron and future input. Input weights change according to spike timing-dependent learning rules during a training period. We characterize the readouts learned under spike timing-dependent synaptic update rules, finding that although the fixed points of learning dynamics are not associated with absolute optimal readouts they convey nearly all of the information conveyed by the optimal readout. Moreover, we find that learned perceptrons transmit position and velocity information of a moving-bar stimulus nearly as efficiently as optimal perceptrons. We conclude that predictive information is, in principle, readable from the perspective of downstream neurons in the absence of other inputs. This suggests an important role for feedforward prediction in sensory encoding.