Podcasts about photoreceptor

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551600v1?rss=1 Authors: Jokura, K., Ueda, N., Guehmann, M., Yanez-Guerra, L. A., Slowinski, P., Wedgwood, K. C., Jekely, G. Abstract: Nitric oxide (NO) produced by nitric-oxide synthase (NOS) is a key regulator of animal physiology. Here we uncover a function for NO in the integration of UV exposure and the gating of a UV-avoidance circuit. We studied UV/violet avoidance mediated by brain ciliary photoreceptors (cPRCs) in larvae of the annelid Platynereis dumerilii. In the larva, NOS is expressed in interneurons (INNOS) postsynaptic to cPRCs. UV stimulation of cPRCs triggers INNOS activation and NO production. NO signals retrogradely to cPRCs to induce their sustained post-stimulus activation through an unconventional guanylate cyclase. This late activation inhibits serotonergic ciliomotor neurons to induce downward swimming. In NOS mutants, retrograde signalling, circuit output and UV avoidance are defective. By mathematical modelling, we recapitulate phototransduction and circuit dynamics in wild-type and mutant larvae. Our results reveal how NO-mediated retrograde signalling gates a synaptic circuit and induces short-term memory of UV exposure to orchestrate light-avoidance behaviour. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.16.549200v1?rss=1 Authors: Yan, J., Lan, W., Yang, Q., Yang, Q., He, X., Dong, Y., Hu, Z., Jiao, K., Paquet-Durand, F. Abstract: Inherited retinal degeneration (IRD) refers to a group of untreatable blinding diseases characterized by a progressive loss of photoreceptors. IRD pathology is often linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na+- and Ca2+-influx, subsequent activation of voltage-gated Ca2+-channels (VGCC), and further Ca2+ influx. However, whether and how exactly intracellular Ca2+ overload contributes to photoreceptor degeneration is still controversial. Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes were linked to several Ca2+-signalling related pathways. To explore this further, organotypic retinal explant cultures derived from rd1 and wt mice were treated with the intracellular Ca2+-chelator BAPTA-AM and with inhibitors for different Ca2+-permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca2+-release-activated channel (CRAC), and Na+/Ca2+ exchanger (NCX). Moreover, we employed the compound NA-184 to selectively inhibit the Ca2+-dependent protease calpain-2. The overall activity of poly(ADP-ribose) polymerases (PARPs), sirtuin-type histone-deacetylases, calpains, as well as the activation of calpain-1, and -2 were analysed in situ on retinal tissue sections. Cell viability was assessed via the TUNEL assay. While rd1 photoreceptor cell death was reduced by BAPTA-AM, the effects of Ca2+-channel blockers were ambiguous, with T-type VGCC and NCX inhibition showing protection, while blocking CNGC and CRAC was detrimental. Activity of calpains and PARPs generally followed similar trends as cell death. Remarkably, sirtuin activity and calpain-1 activation was associated with photoreceptor protection, while calpain-2 activity was linked to degeneration. Accordingly, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors. Together, these results indicate that Ca2+ overload in rd1 photoreceptors may be triggered by T-type VGCC in conjunction with NCX. High Ca2+-levels likely suppress the protective activity of calpain-1 and promote neurodegeneration via activation of calpain-2. Our study details the complexity of Ca2+-signalling in photoreceptors and emphasizes the importance of identifying and targeting degenerative processes to achieve a therapeutic benefit for IRD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.02.547380v1?rss=1 Authors: Lewis, T. R., Makia, M. S., Castillo, C. M., Hao, Y., Al-Ubaidi, M. R., Skiba, N. P., Conley, S. M., Arshavsky, V. Y., Naash, M. I. Abstract: Visual signal transduction takes place within a stack of flattened membranous "discs" enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large hetero-oligomeric complexes of two homologous tetraspanin proteins, PRPH2 (a.k.a. peripherin-2 or rds) and ROM1. While mutations in PRPH2 affect the formation of disc rims, the role of ROM1 remains poorly understood. In this study, we found that the knockout of ROM1 causes a compensatory increase in the disc content of PRPH2. Despite this increase, discs of ROM1 knockout mice displayed a delay in disc enclosure associated with a large diameter and lack of incisures in mature discs. Strikingly, further increasing the level of PRPH2 rescued these morphological defects. We next showed that disc rims are still formed in a knockin mouse in which the tetraspanin body of PRPH2 was replaced with that of ROM1. Together, these results demonstrate that, despite its contribution to the formation of disc rims, ROM1 can be replaced by an excess of PRPH2 for timely enclosure of newly forming discs and establishing normal outer segment structure. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.25.546469v1?rss=1 Authors: Crespo, E. L., Pal, A., Prakash, M., Silvagnoli, A. D., Zaidi, Z., Gomez-Ramirez, M., Tree, M. O., Shaner, N. C., Lipscombe, D., Moore, C. I., Hochgeschwender, U. Abstract: We developed a platform that utilizes a calcium-dependent luciferase to convert neuronal activity into activation of light sensing domains within the same cell. The platform is based on a Gaussia luciferase variant with high light emission split by calmodulin-M13 sequences that depends on influx of calcium ions (Ca2+) for functional reconstitution. In the presence of its luciferin, coelenterazine (CTZ), Ca2+ influx results in light emission that drives activation of photoreceptors, including optogenetic channels and LOV domains. Critical features of the converter luciferase are light emission low enough to not activate photoreceptors under baseline condition and high enough to activate photosensing elements in the presence of Ca2+ and luciferin. We demonstrate performance of this activity-dependent sensor and integrator for changing membrane potential and driving transcription in individual and populations of neurons in vitro and in vivo. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.06.535932v1?rss=1 Authors: Lewis, T. R., Phan, S., Castillo, C. M., Kim, K.-Y., Coppenrath, K., Thomas, W., Hao, Y., Skiba, N. P., Horb, M. E., Ellisman, M. H., Arshavsky, V. Y. Abstract: The first steps of vision take place within a stack of tightly packed disc-shaped membranes, or "discs", located in the outer segment compartment of photoreceptor cells. In rod photoreceptors, discs are enclosed inside the outer segment and contain deep indentations in their rims called "incisures". The presence of incisures has been documented in a variety of species, yet their role remains elusive. In this study, we combined traditional electron microscopy with three-dimensional electron tomography to demonstrate that incisures are formed only after discs become completely enclosed. We also observed that, at the earliest stage of their formation, discs are not round as typically depicted but rather are highly irregular in shape and resemble expanding lamellipodia. Using genetically manipulated mice and frogs and measuring outer segment protein abundances by quantitative mass spectrometry, we further found that incisure size is determined by the molar ratio between peripherin-2, a disc rim protein critical for the process of disc enclosure, and rhodopsin, the major structural component of disc membranes. While a high perpherin-2 to rhodopsin ratio causes an increase in incisure size and structural complexity, a low ratio precludes incisure formation. Based on these data, we propose a model whereby normal rods express a modest excess of peripherin-2 over the amount required for complete disc enclosure in order to ensure that this important step of disc formation is accomplished. Once the disc is enclosed, the excess peripherin-2 incorporates into the rim to form an incisure. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.27.525802v1?rss=1 Authors: Krylov, A. J., Yu, S., Newton, A. H., He, j., Jusuf, P. R. Abstract: Loss of neurons in the neural retina is a leading cause of vision loss. While humans do not possess the capacity for retinal regeneration, zebrafish can achieve this through activation of resident Muller glia. Remarkably, despite the presence of Muller glia in humans and other mammalian vertebrates, these cells lack an intrinsic ability to contribute to regeneration. Upon activation, zebrafish Muller glia can adopt a stem cell-like state, undergo proliferation and generate new neurons. However, the underlying molecular mechanisms of this activation subsequent retinal regeneration remains unclear. To address this, we performed single-cell RNA sequencing (scRNA-seq) and report remarkable heterogeneity in gene expression within quiescent Muller glia across distinct dorsal, central and ventral retina pools of such cells. Next, we utilised a genetically driven, chemically inducible nitroreductase approach to study Muller glia activation following selective ablation of three distinct photoreceptor subtypes: long wavelength sensitive cones, short wavelength sensitive cones, and rods. There, our data revealed that a region-specific bias in activation of Muller glia exists in the zebrafish retina, and this is independent of the distribution of the ablated cell type across retinal regions. Notably, gene ontology analysis revealed that injury-responsive dorsal and central Muller glia express genes related to dorsal/ventral pattern formation, growth factor activity, and regulation of developmental process. Through scRNA-seq analysis, we identify a shared genetic program underlying initial Muller glia activation and cell cycle entry, followed by differences that drive the fate of regenerating neurons. We observed an initial expression of AP-1 and injury-responsive transcription factors, followed by genes involved in Notch signalling, ribosome biogenesis and gliogenesis, and finally expression of cell cycle, chromatin remodeling and microtubule-associated genes. Taken together, our findings document the regional specificity of gene expression within quiescent Muller glia and demonstrate unique Muller glia activation and regeneration features following neural ablation. These findings will improve our understanding of the molecular pathways relevant to neural regeneration in the retina. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.20.521190v1?rss=1 Authors: Rother, L., Müller, R., Kirschenmann, E., Kaya-Zeeb, S., Thamm, M., Pfeiffer, K. Abstract: The behavioral state of an animal has profound effects on neuronal information processing. Locomotion changes the response properties of visual interneurons in the insect brain, but it is still unknown if it also alters the response properties of photoreceptors. Photoreceptor responses become faster at higher temperatures. It has therefore been suggested that thermoregulation in bees and other insects could improve temporal resolution in vision, but direct evidence for this idea has so far been missing. Here we compared electroretinograms (ERGs) from the compound eyes of tethered bumblebees that were either sitting still or were walking on an air supported ball. We found that the visual processing speed strongly increased when the bumblebees were walking. By monitoring the bumblebees' eye temperature during our recordings, we saw that the increase in response speed was in synchrony with a rise of the eye temperature. By artificially heating the bee's head, we show that the walking induced temperature increase of the visual system is sufficient to explain the rise in processing speed. We also show that walking accelerates the visual system to the equivalent of a 14-fold increase in light intensity. We conclude that the walking-induced rise in temperature accelerates the processing of visual information in bumblebees, which is an ideal strategy to process the increased information flow during locomotion. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.21.517374v1?rss=1 Authors: Spencer, W. J., Schneider, N. F., Skiba, N. P., Arshavsky, V. Y. Abstract: The photoreceptor outer segment is a modified cilium filled with hundreds of flattened disc membranes responsible for efficient light capture. To maintain photoreceptor health and functionality, outer segments are continuously renewed through the addition of new discs at their base. This process is driven by branched actin polymerization nucleated by the Arp2/3 complex. To induce actin polymerization, Arp2/3 requires a nucleation promoting factor. Here, we show that the nucleation promoting factor driving disc morphogenesis is the pentameric WAVE complex and identify all protein subunits of this complex. We further demonstrate that the knockout of one of them, WASF3, abolishes actin polymerization at the site of disc morphogenesis leading to formation of disorganized membrane lamellae emanating from the photoreceptor cilium instead of an outer segment. These data establish that, despite the intrinsic ability of photoreceptor ciliary membranes to form lamellar structures, WAVE-dependent actin polymerization is essential for organizing these membranes into a proper outer segment. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.10.516027v1?rss=1 Authors: Asteriti, S., Marino, V., Avesani, A., Biasi, A., Dal Cortivo, G., Cangiano, L., Dell'Orco, D. Abstract: Retinal dystrophies of genetic origin are often associated with mutations in the genes involved in the phototransduction cascade in photoreceptors, a paradigmatic signaling pathway mediated by G protein-coupled receptors. Photoreceptor viability is strictly dependent on the levels of the second messengers cGMP and Ca2+. Here we explored the possibility of modulating the phototransduction cascade in mouse rods using direct or liposome-mediated administration of a recombinant protein crucial for regulating the interplay of the second messengers in photoreceptor outer segments. The effects of administration of the free and liposome-encapsulated human guanylate cyclase-activating protein (GCAP1) were compared in biological systems of increasing complexity (in cyto, ex vivo, and in vivo). Analysis of protein biodistribution and direct measurement of functional alteration in rod photoresponses show that the exogenous GCAP1 protein is fully incorporated into the mouse retina and photoreceptor outer segments. Furthermore, only in the presence of a point mutation associated with cone-rod dystrophy in humans p.(E111V), protein delivery induces a disease-like electrophysiological phenotype, consistent with constitutive activation of the retinal guanylate cyclase. Our study demonstrates that both direct and liposome-mediated protein delivery are powerful tools for targeting signaling cascades in neuronal cells, which could be particularly important for the treatment of autosomal dominant genetic diseases. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.10.516020v1?rss=1 Authors: Megaw, R., Moye, A., Zhang, Z., Newton, F., McPhie, F., Murphy, L. C., McKie, L., He, F., Jungnickel, M. K., von Kriegsheim, A., Machesky, L., Wensel, T. G., Mill, P. Abstract: As signalling organelles, primary cilia regulate their membrane G protein-coupled receptor (GPCR) content by ectocytosis, a process requiring localised actin dynamics at their tip to alter membrane shape.(1, 2) Mammalian photoreceptor outer segments comprise an expanse of folded membranes (discs) at the tip of highly-specialised connecting cilia (CC), in which photosensitive GPCRs like rhodopsin are concentrated. In an extraordinary feat of biology, outer segment discs are shed and remade daily.(3) Defects in this process, due to genetic mutations, cause retinitis pigmentosa (RP), an untreatable, blinding disease. The mechanism by which photoreceptor cilia generate outer segments is therefore fundamental for vision yet poorly understood. Here, we show the membrane deformation required for outer segment disc genesis is driven by dynamic changes in the actin cytoskeleton in a process akin to ectocytosis. Further, we show RPGR, a leading causal RP gene, regulates activity of actin binding proteins crucial to this process. Disc genesis is compromised in Rpgr mouse models, slowing the actin dynamics required for timely disc formation, leading to aborted membrane shedding as ectosome-like vesicles, photoreceptor death and visual loss. Manipulation of actin dynamics partially rescues the phenotype, suggesting this pathway could be targeted therapeutically. These findings help define how actin-mediated dynamics control outer segment turnover. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The Journal RETINA is devoted exclusively to diseases of the retina and vitreous. These podcasts are intended to bring to its listeners summaries of selected articles published in the current issue of this internationally acclaimed journal.

Have you ever got a horrible mosquito bite whilst on holiday and wondered 'why me again?' And was your travel buddy someone who never got one? It could very well be to do with their fashion sense. Anoushka Handa spoke to Jeff Riffell to find out more... Like this podcast? Please help us by supporting the Naked Scientists

Learn about how a ghosted email causes different stress than a rude response does, the 15-year grudge match between rival dino hunters known as The Bone Wars, and crown shyness, the forest’s version of social distancing. Ignoring someone's email and drafting a rude response stress people out in similar but different ways by Kelsey Donk What new research reveals about rude workplace emails. (2020). ScienceDaily. https://www.sciencedaily.com/releases/2020/09/200925113648.htm  Yuan, Z., Park, Y., & Sliter, M. T. (2020). Put you down versus tune you out: Further understanding active and passive e-mail incivility. Journal of Occupational Health Psychology, 25(5), 330–344. https://doi.org/10.1037/ocp0000215 Zhenyu Yuan,YoungAh Park. (2020, July 21). The Psychological Toll of Rude E-mails. Scientific American. https://www.scientificamerican.com/article/the-psychological-toll-of-rude-e-mails/  The Bone Wars Were a 15-Year Grudge Match Between Rival Dino Hunters by Reuben Westmaas The Two Paleontologists Who Had a Bone to Pick with Each Other | Detours | Prehistoric Road Trip. (2020, June 7). WTTW Chicago. https://interactive.wttw.com/prehistoric-road-trip/detours/the-two-paleontologists-who-had-a-bone-to-pick-with-each-other  Engber, D. (2013, August 7). A Brilliant Paleontologist, Unfit for Battle in the Bone Wars. Slate Magazine; Slate. https://slate.com/business/2013/08/dinosaur-bone-wars-othniel-charles-marsh-edward-drinker-cope-and-their-forgotten-rival.html  Crown shyness is how trees practice social distancing by Steffie Drucker McVean, A. (2018, September 19). Trees avoid touching each other due to "crown shyness." The results are beautiful webs of leaves. Office for Science and Society. https://www.mcgill.ca/oss/article/did-you-know/trees-avoid-touching-each-other-due-crown-shyness-results-are-beautiful-webs-leaves  Osterloff, Emily. (2020) Crown shyness: are trees social distancing too? Nhm.Ac.Uk. https://www.nhm.ac.uk/discover/crown-shyness-are-trees-social-distancing.html  Wu, K. (2020, July 6). Some trees may “social distance” to avoid disease. Nationalgeographic.com. https://www.nationalgeographic.com/science/2020/07/tree-crown-shyness-forest-canopy/  MENG, S. X., RUDNICKI, M., LIEFFERS, V. J., REID, D. E. B., & SILINS, U. (2006). Preventing crown collisions increases the crown cover and leaf area of maturing lodgepole pine. Journal of Ecology, 94(3), 681–686. https://doi.org/10.1111/j.1365-2745.2006.01121.x  ‌Crepy, M. A., & Casal, J. J. (2014). Photoreceptor-mediated kin recognition in plants. New Phytologist, 205(1), 329–338. https://doi.org/10.1111/nph.13040  Ballare, C. L., Sanchez, R. A., Scopel, A. L., Casal, J. J., & Ghersa, C. M. (1987). Early detection of neighbour plants by phytochrome perception of spectral changes in reflected sunlight. Plant, Cell and Environment, 10(7), 551–557. https://doi.org/10.1111/1365-3040.ep11604091  Subscribe to Curiosity Daily to learn something new every day with Ashley Hamer and Natalia Reagan (filling in for Cody Gough). You can also listen to our podcast as part of your Alexa Flash Briefing; Amazon smart speakers users, click/tap “enable” here: https://www.amazon.com/Curiosity-com-Curiosity-Daily-from/dp/B07CP17DJY  See omnystudio.com/listener for privacy information.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.03.366682v1?rss=1 Authors: Rhim, I., Coello-Reyes, G., Nauhaus, I. Abstract: Visual input to primary visual cortex (V1) depends on highly adaptive filtering in the retina. In turn, isolation of V1 computations to study cortical circuits requires control over retinal adaption and its corresponding spatio-temporal-chromatic output. Here, we first measure the balance of input to V1 from the three main photoreceptor opsins (M-opsin, S-opsin, and rhodopsin) as a function of light adaption and retinotopy. Results show that V1 is rod-mediated in common laboratory settings, yet cone-mediated in natural daylight, as evidenced by exclusive sensitivity to UV wavelengths via cone S-opsin in the upper visual field. Next, we show that cone-mediated V1 responds to 2.5-fold higher temporal frequencies than rod-mediated V1. Furthermore, cone-mediated V1 has smaller RFs, yet similar spatial frequency tuning. V1 responses in rod-deficient (Gnat1-/-) mice confirm that the effects are due to differences in photoreceptor contribution. This study provides foundation for using mouse V1 to study cortical circuits. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.13.337865v1?rss=1 Authors: Altschuler, S. J., Ji, W., Wu, L. F. Abstract: During development, neurons extend in search of synaptic partners. Precise control of axon extension velocity can therefore be crucial to ensuring proper circuit formation. How velocity is regulated - particularly by the extending axons themselves - remains poorly understood. Here, we investigate this question in the Drosophila visual system, where photoreceptors make precise connections with a specific set of synaptic partners that together create a circuit underpinning neural superposition (NSP). We used a combination of genetic perturbations and quantitative image analysis to investigate the influence of cell identity on growth cone velocity and subsequent spatial-temporal coincidence of presynaptic and postsynaptic neurons. Our study provides a case study of how cell autonomous properties of presynaptic axons play a pivotal role in controlling the dynamics of growing axons and determining the formation of a precise neuronal circuit. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.07.329821v1?rss=1 Authors: Aguirre, G. D., Cideciyan, A. V., Dufour, V. L., Ripolles Garcia, A., Sudharsan, R., Swider, M., Nikonov, R., Iwabe, S., Boye, S. L., Hauswirth, W. W., Jacobson, S. G., Beltran, W. A. Abstract: The inherited childhood blindness caused by mutations in NPHP5, a form of Leber congenital amaurosis, results in abnormal development, dysfunction and degeneration of photoreceptors. A naturally occurring NPHP5 mutation in dogs results in a phenotype that very nearly duplicates the human retinopathy in terms of the photoreceptors involved, spatial distribution of degeneration and the natural history of vision loss. We show that AAV-mediated NPHP5 gene augmentation of mutant canine retinas at the time of active degeneration and peak cell death stably restores photoreceptor structure, function, and vision with either the canine or human NPHP5 transgenes. Mutant cone photoreceptors, which failed to form outer segments during development, reform this structure after treatment. Degenerating rod photoreceptor outer segments are stabilized and develop normal structure. This process begins within 8 weeks following treatment, and remains stable throughout the 6 month post treatment period. In both photoreceptor cell classes, mislocalization of rod and cone opsins is minimized or reversed. Retinal function and functional vision are restored. Efficacy of gene therapy in this large animal ciliopathy model of Leber congenital amaurosis provides a path for translation to human treatment. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.22.308726v1?rss=1 Authors: Zerti, D., Hilgen, G., Dorgau, B., Collin, J., Ader, M., Armstrong, L., Sernagor, E., Lako, M. Abstract: Retinal dystrophies often lead to blindness. Developing therapeutic interventions to restore vision is therefore of paramount importance. Here we demonstrate the ability of pluripotent stem cell-derived cone precursors to engraft and restore light responses in the Pde6brd1 mouse, an end-stage photoreceptor degeneration model. Up to 1.5% of precursors integrated into the host retina, differentiated into cones and formed synapses with bipolar cells. Half of the transplanted mice exhibited visual behaviour and 33% showed binocular light sensitivity. The majority of ganglion cells exhibited contrast-sensitive ON, OFF or ON-OFF light responses and even motion sensitivity. Many cells also exhibited unusual responses (e.g. light-induced suppression), presumably reflecting remodelling of the neural retina. Our data indicate that despite relatively low engraftment yield, engrafted pluripotent stem cell-derived cone precursors can elicit light responsiveness even at advanced degeneration stages. Further work is needed to improve engraftment yield and counteract retinal remodelling to achieve useful clinical applications. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.05.238352v1?rss=1 Authors: Emmerich, K. B., White, D. T., Kambhamptati, S. P., Lee, G. Y., Fu, T.-M., Sahoo, A., Betzig, E., Kannan, R. M., Mumm, J. S., Saxena, M. T. Abstract: Retinal regeneration occurs naturally in zebrafish but not in mammals. A thorough understanding of the mechanisms regulating regeneration may help to advance strategies for stimulating retinal repair in humans. We previously implicated microglia as key regulators of retinal regeneration using a zebrafish model of inducible photoreceptor degeneration. Intriguingly, post-injury treatments with the immune suppressant dexamethasone (Dex) resulted in accelerated photoreceptor regeneration. Modifying microglia responses to retinal cell death may therefore promote neuroregenerative processes. Here, we investigated the effect of Dex on microglia reactivity in the regenerating zebrafish retina using adaptive optics-corrected lattice light-sheet microscopy. Quantitative analysis of in vivo time-lapse imaging data revealed that Dex inhibited microglia migration speed, consistent with an immunosuppressive effect. Unfortunately, long-term treatment with glucocorticoids, including Dex, causes adverse side effects which limits their use therapeutically. To overcome this limitation, a nanoparticle-based drug delivery strategy was used to target Dex to reactive microglia. We show that conjugating Dex to dendrimer nanoparticles: 1) dramatically decreased toxicity in larval zebrafish, 2) succeeded in selective targeting of reactive microglia and, 3) resulted in super-accelerated photoreceptor regeneration kinetics. These data support the use of dendrimer-based drug formulations for modulating microglia reactivity in degenerative disease contexts, especially as therapeutic strategies for promoting regenerative responses to neuronal cell loss. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.28.121673v1?rss=1 Authors: Leinonen, H., Pham, N. C., Boyd, T., Santoso, J., Palczewski, K., Vinberg, F. Abstract: Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cell dendrites expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed these issues in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network reminiscent of the neurodevelopmental state as well as potentiation of rod - rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. The results implicate retinal adaptation leading to persistent visual function during photoreceptor degenerative disease. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.30.069385v1?rss=1 Authors: Sasaki, Y., Kakita, H., Kubota, S., Sene, A., Lee, T. J., Ban, N., Dong, Z., Lin, J. B., Boye, S. L., DiAntonio, A., Boye, S. E., Apte, R. S., Milbrandt, J. Abstract: Leber congenital amaurosis type 9 (LCA9) is an autosomal recessive, early onset retinal neurodegenerative disease caused by mutations in the gene encoding the nuclear NAD+ synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1 and its role in NAD+ homeostasis, LCA9 patients do not manifest pathologies other than retinal degeneration. To investigate the mechanism of degeneration, we examined retinas of developing and adult mice with conditional or tissue-specific NMNAT1 loss. Widespread NMNAT1 depletion in adult mice resulted in loss of photoreceptors, indicating these cells are exquisitely vulnerable to NMNAT1 loss. NMNAT1 is required within the photoreceptor, as conditional deletion of NMNAT1 in photoreceptors but not retinal pigment epithelial cells is sufficient to cause photoreceptor neurodegeneration and vision loss. Moreover, delivery of NMNAT1 into eyes of adult mice lacking NMNAT1 using a modified AAV8 vector containing a photoreceptor-specific promoter rescued the retinal degeneration phenotype and partially restored vision. Finally, we defined the molecular mechanism driving photoreceptor cell death. Loss of NMNAT1 activates SARM1, an inducible NADase best known as the central executioner of axon degeneration. SARM1 is required for the photoreceptor death and vision loss that occurs following NMNAT1 deletion. This surprising finding demonstrates that the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, and establishes a commonality of mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway that is active in the setting of dysregulated NAD+ metabolism and identifies SARM1 as a therapeutic candidate for the treatment of retinal degeneration. Copy rights belong to original authors. Visit the link for more info

Co-hosts John and Tracy Suchocki interview professor Raj Rajeshwar, one of the leading researchers in the exciting area of solar fuels, which are fuels generated directly from sunlight. We explore the chemistry behind the many challenges still faced in the development of solar fuels. We talk about the prospects. About the possibilities. This is perhaps one of our more technical episodes. It assumes the listener has a basic understanding of chemical reactions, particularly oxidations and reductions. But for all listeners, much value and insight is provided. Duration: 47:39.

We are solar powered beings! But we now spend 93% of our lives INDOORS.   Brilliant founder of Sauna Space, Brian Richards, takes us through the fascinating body-wide healing phenomena of red light therapy. We cover all the science, the applications, and the specifics of how biologically relevant light (found largely in firelight, sunrise, and sunset) can cause massive changes in cell behavior, function, and repair. There are hundreds of research studies on this subject. Over 400 gold-standard, placebo-controlled clinical trials exist on this subject. It's only a matter of time before we see tanning salons and 7-Elevens popping up with this sort of therapy. Learn the facts now and become a savvy consumer on the good stuff.   Our bodies are solar panels that need to be fueled by the light that nourishes them.     If after this episode, you feel compelled to order a SaunaSpace product of your own, you can use promo code "AMRONMD" to receive a discount on your order.

Dr. Winslow Briggs is Director Emeritus of the Carnegie Institution Of Science. He received his Ph.D. in Biology from Harvard University. He has served on the faculty at Harvard University and is a Professor of Biology Emeritus at Stanford University. Winslow has been the recipient of many awards and honors over the course of his career. He is an elected Member of the  U.S. National Academy of Science, a Member of the American Academy of Arts and Sciences, a Member of the German Academy of Sciences Leopoldina, and a Fellow of the California Academy of Sciences. In addition, he was awarded International Prize for Biology from the Japan Society for the Promotion of Science, the Adolph E. Gude Jr. Award from the American Society of Plant Biologists, an honorary doctorate degree from the University of Freiberg, the Finsen Medal from the International Association of Photobiology, the Sterling Hendricks Medal from the U.S. Department of Agriculture and the American Chemical Society, the Stephen Hales Prize from the American Society of Plant Physiologists, the Alexander von Humboldt Senior Scientist Award, and a Guggenheim Fellowship. Winslow is here with us today to talk share his passion for research and tell us about his experiences in life and science.

What are colours? What is colour? Just different wavelengths of light...mental (Wikipedia) Visible light (NASA) The visible spectrum (Wikipedia) What is electromagnetic radiation? (livescience) Spectral colours (HyperPhysics, Georgia State University) What wavelength goes with a colour? (NASA) Rabbit & Spaghetti Shiraz (Naked Wines) This is your brain on nature (National Geographic) Your colour red could really be my blue (livescience) How my friends described colours to me when I couldn't see (li.st) How colours get their names (livescience) Colour vision in humans & other species (Wikipedia) A nice overview on rods & cones (HyperPhysics, Georgia State University) How do we see colour? (livescience) Photoreceptor cells (Wikipedia) Bayer filter mosaics: How red, green & blue is arranged on our screens to complement our colour vision (Wikipedia) Theory of colours (Wikipedia) Newton & the colour spectrum (Web Exhibits) Newton's theory of light: His experiment split white light through a prism to make a rainbow, then recombined it through another prism to make white light again (The Star Garden) Michelangelo Merisi da Caravaggio (Caravaggio Foundation) Dark Side of the Moon, Pink Floyd (Ultimate Classic Rock) Red light is just a photon of a certain energy: The wavelength of red light is 650 nm, blue is 475 nm & green is 510 nm (Montgomery Blair High School) Can you hear colour? Some people with 'synesthesia' claim to be able to (livescience) What is synesthesia? (Scientific American) Human ears respond to frequencies of sound between about 20 Hz to 20,000 Hz (Wikipedia) Human eyes respond to wavelengths of light between about 390 nm to 700 nm (Wikipedia) What is infrared light? It's just below (longer than) the wavelength of visible red light, so humans can't see it (Wikipedia) Infrared waves (NASA) Night vision goggles 'extend' your vision into the infrared (Wikipedia) Humans give off infrared radiation (Science Questions With Surprising Answers) The longest waves are 'radio waves', further along than infrared - they're still photons of energy, we just can't see them (livescience) Radio waves (NASA) Shorter waves than blue are 'ultraviolet' (UV), they're at a shorter wavelength/higher energy than we can see (NASA) What is ultraviolet light? (livescience) Do rainbows have ultraviolet bands & infrared bands? (Physics StackExchange) Shorter waves than UV are X-rays, they're at a shorter wavelength/higher energy than we can see (NASA) The shortest waves are 'gamma waves', they're still photons of energy, we just can't see them (NASA) We need different types of telescopes to 'see' the different types of waves in the universe: radio, infrared, visible, X-ray, gamma (NASA) Mantis shrimps & bees can see UV light (Catalyst) The absorption spectrum of water: There's an interesting dip right at the wavelengths of visible light (Wikipedia) The absorption spectrum of water (London Southbank University) Transparency of water in the visible range (HyperPhysics, Georgia State University) Some creatures are 'pentachromats', i.e. they have 5 different types of colour receptors in their eyes (Wikipedia) What is melanopsin? (Wikipedia) Melanopsin probably evolved ~1 billion years prior to cone cells: These receptors independently gauge the amount of blue or yellow incoming light & route this information to parts of the brain involved in emotions & the regulation of the circadian rhythm (livescience) Someone who is colour blind is missing 1 or more of the 3 sets of colour-sensing cones (Wikipedia) How we see colours: Light absorption, reflection & transmission (the Physics Classroom) Sunderland claims the first stained glass in England (BBC, Radio 4) Sunderland National Glass Centre Visible light & the eye's response (the Physics Classroom) You can't mix all the colours & get white paint (Reference) Why does mixing every paint colour produce grey not white? (Physics StackExchange) White light is all of the frequencies of light (Reference) The colours of light (Science Learning) Colour: Travels through the paintbox - the book Johnny mentioned (Victoria Finlay) Photodegradation, "the alteration of materials by photons of light", is why colours fade (Wikipedia) Photodegradation & photostabilisation of polymers: A proper sciencey paper (SpringerPlus) Some answers to the question 'Why does colour fade when left in sunlight?' (Reddit) What is ink? (Wikipedia) What are dyes? (Encyclopaedia Britannica) Why are plants green? Because they absorb red light & reflect green light from the sun! (UCSB ScienceLine) More detailed answers to why plants are green (ResearchGate) Blue sky & Rayleigh scattering (HyperPhysics, Georgia State University) Goat moisturing lotion (The Goat Skincare) A history of inks, dyes & pigments (World of Chemicals) People have been dyeing fabric indigo blue for 6,000 years (The New York Times) Effect of light exposure on paintings (National Gallery of Art) What is oil painting? (Encyclopaedia Britannica) Pigments used by different artists, including Caravaggio (Pigments through the Ages) Printed photos fade, but so too can photos saved to disk! (Bloomberg) Cultures see & name colours differently (BBC, Future) Newton & the indigo controversy (Wikipedia) Italian, Russian & Hebrew has 12 basic colour terms (English has 11) & they distinguish blue & azure (Wikipedia) Colour naming: Azure is distinct from blue in Russian & Italian, but not English (Wikipedia) Eskimo words for snow...could be a myth (Wikipedia) How many words do the Inuits have for snow? (The Guardian) What's in a colour? The unique human health effects of blue light (Environmental Health Perspectives) This article suggests penguins can see violet, green & blue, but not red (National Wildlife Federation) This is what I was trying to explain to Johnny, quite poorly, "...even if you perceive the sky as the colour someone else would call 'red', your blue sky still makes you feel calm", because of the 'blue' frequency of the light (livescience) Where are you from? Send us a postcard! Strange Attractor, c/ PO Box 9, Fitzroy, VIC 3065, Australia Corrections The human retina contains ~120 million rod cells, not 15 million (Wikipedia) Cheeky review? (If we may be so bold) It'd be amazing if you gave us a short review...it'll make us easier to find in iTunes: Click here for instructions. You're the best! We owe you a free hug and/or a glass of wine from our cellar Click to subscribe in iTunes

Richard Neutze discusses a structural analysis of light-induced structural changes in the visual pigment rhodopsin.

From the beauty of a sunset or the ugliness of war to the smile on a loved one's face, our eyes bring us all kinds of information about the world around us. now researchers are working to develop new therapies for people who have lost this precious sense. Plus, smelling elephants, marmoset twins, and an all-seeing gene of the month. Like this podcast? Please help us by supporting the Naked Scientists

Purpose: To analyze the correlation between morphological and functionalresults 12 months after epiretinal membrane (ERM) surgery. Methods: 31eyes from 31 consecutive patients with nnetamorphopsia and bestcorrected visual acuity (BCVA) below 20/32 underwent a transconjunctival23-gauge vitrectomy with ERM and internal limiting membrane peeling. Preoperatively and 3, 6 and 12 months postoperatively, we assessed BCVA,microperimetry (MP-1) and spectral domain optical coherence tomography(SD-OCT). Photoreceptor inner and outer segment (IS/OS) was graded onSD-OCT images and correlated with microperimetry measurements in thefovea and parafoveal region. Results: The postoperative BCVA wassignificantly better in eyes with an intact IS/OS junction (p < 0.01).In addition, the mean defect depth was postoperatively decreased in thefoveal and parafoveal area in eyes with an intact IS/OS junction. Acorrelation of SD-OCT IS/OS images and microperinnetry in eyes withimprovement in BCVA of at least 2 lines revealed a statisticallysignificant result for the parafoveal quadrants (p < 0.011 for SD-OCTand p < 0.005 for microperimetry) but not for the foveal area alone.Conclusions: The IS/OS regeneration in the parafoveal quadrantscontributes significantly to the recovery of BCVA following ERM surgery.Consequently, functional and morphological tests of the macular areashould not be limited to the fovea but should be extended to theparafoveal region.

Thu, 26 Apr 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/14413/ https://edoc.ub.uni-muenchen.de/14413/1/Ohler_Stephan.pdf Ohler, Stephan ddc:570, ddc:500, Fakultät für Biologie

Cambridge Neuroscience in association with the British Neuroscience Association was delighted to welcome Professor Russell Foster from the University of Oxford to deliver the public neuroscience lecture at the annual Cambridge Neuroscience Seminar, which was held on March 20th at the Babbage Lecture Theatre in Cambridge. Russell Foster is Professor of Circadian Neuroscience and Head of the Nuffield Laboratory of Ophthalmology at the University of Oxford. Russell's research interests span the neurosciences but are currently focused upon two broad themes. The first relates to how environmental light is detected and processed by vertebrate photoreceptors. The second line of research relates to how circadian rhythms and sleep are generated and their disruption in mental illness and neurodegenerative disease.