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Retinal regeneration

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https://www.readbyqxmd.com/read/27904478/neuro-rejuvenation-for-neuronal-function
#1
REVIEW
Yuan Liu, Richard K Lee
Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell (RGC) death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27895551/oct4-methylation-mediated-silencing-as-an-epigenetic-barrier-preventing-m%C3%A3-ller-glia-dedifferentiation-in-a-murine-model-of-retinal-injury
#2
Luis I Reyes-Aguirre, Monica Lamas
Müller glia (MG) is the most abundant glial type in the vertebrate retina. Among its many functions, it is capable of responding to injury by dedifferentiating, proliferating, and differentiating into every cell types lost to damage. This regenerative ability is notoriously absent in mammals. We have previously reported that cultured mammalian MG undergoes a partial dedifferentiation, but fails to fully acquire a progenitor phenotype and differentiate into neurons. This might be explained by a mnemonic mechanism comprised by epigenetic traits, such as DNA methylation...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27893779/rapid-recovery-of-visual-function-associated-with-blue-cone-ablation-in-zebrafish
#3
Gordon F Hagerman, Nicole C L Noel, Sylvia Y Cao, Michèle G DuVal, A Phillip Oel, W Ted Allison
Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous...
2016: PloS One
https://www.readbyqxmd.com/read/27886185/hyper-il-6-a-potent-and-efficacious-stimulator-of-rgc-regeneration
#4
D Fischer
Mature retinal ganglion cells (RGCs) normally fail to regenerate injured axons and die soon after optic nerve injury. Research over the last two decades has demonstrated that application of IL-6-like cytokines or activation of respective downstream signaling pathways promote neuroprotection and optic nerve regeneration. However, the overall beneficial effects of natural cytokines remain usually rather moderate, possibly due to intrinsic signaling pathway inhibitors, such as PTEN or SOCS3, or a limited expression of specific cytokine receptors in RGCs...
November 25, 2016: Eye
https://www.readbyqxmd.com/read/27880821/inhibition-of-the-tgf%C3%AE-pathway-enhances-retinal-regeneration-in-adult-zebrafish
#5
Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp
In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish...
2016: PloS One
https://www.readbyqxmd.com/read/27876464/m%C3%A3-ller-stem-cell-dependent-retinal-regeneration
#6
REVIEW
Annu Chohan, Usha Singh, Atul Kumar, Jasbir Kaur
Müller Stem cells to treat ocular diseases has triggered enthusiasm across all medical and scientific communities. Recent development in the field of stem cells has widened the prospects of applying cell based therapies to regenerate ocular tissues that have been irreversibly damaged by disease or injury. Ocular tissues such as the lens and the retina are now known to possess cell having remarkable regenerative abilities. Recent studies have shown that the Müller glia, a cell found in all vertebrate retinas, is the primary source of new neurons, and therefore are considered as the cellular basis for retinal regeneration in mammalian retinas...
November 19, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27834958/regenerating-reptile-retinas-a-comparative-approach-to-restoring-retinal-ganglion-cell-function
#7
D L Williams
Transection or damage to the mammalian optic nerve generally results in loss of retinal ganglion cells by apoptosis. This cell death is seen less in fish or amphibians where retinal ganglion cell survival and axon regeneration leads to recovery of sight. Reptiles lie somewhere in the middle of this spectrum of nerve regeneration, and different species have been reported to have a significant variation in their retinal ganglion cell regenerative capacity. The ornate dragon lizard Ctenophoris ornatus exhibits a profound capacity for regeneration, whereas the Tenerife wall lizard Gallotia galloti has a more variable response to optic nerve damage...
November 11, 2016: Eye
https://www.readbyqxmd.com/read/27830507/vitamin-a-and-vision
#8
John C Saari
Visual systems detect light by monitoring the effect of photoisomerization of a chromophore on the release of a neurotransmitter from sensory neurons, known as rod and cone photoreceptor cells in vertebrate retina. In all known visual systems, the chromophore is 11-cis-retinal complexed with a protein, called opsin, and photoisomerization produces all-trans-retinal. In mammals, regeneration of 11-cis-retinal following photoisomerization occurs by a thermally driven isomerization reaction. Additional reactions are required during regeneration to protect cells from the toxicity of aldehyde forms of vitamin A that are essential to the visual process...
2016: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/27809489/structural-insights-into-the-drosophila-melanogaster-retinol-dehydrogenase-a-member-of-the-short-chain-dehydrogenase-reductase-family
#9
Lukas Hofmann, Yaroslav Tsybovsky, Nathan S Alexander, Darwin Babino, Nicole Yishi Leung, Craig Montell, Surajit Banerjee, Johannes von Lintig, Krzysztof Palczewski
The 11-cis-retinylidene chromophore of visual pigments isomerizes upon interaction with a photon, initiating a downstream cascade of signaling events that ultimately lead to visual perception. 11-cis-Retinylidene is regenerated through the enzymatic transformations collectively called visual cycle. The first and rate-limiting enzymatic reaction within this cycle, i.e. the reduction of all-trans-retinal to all-trans-retinol, is catalyzed by retinol dehydrogenases. Here, we solved the structure of Drosophila melanogaster photoreceptor retinol dehydrogenase (PDH) isoform C (PDHc) that belongs to the short-chain dehydrogenase/reductase (SDR) family...
November 3, 2016: Biochemistry
https://www.readbyqxmd.com/read/27798125/reconnecting-eye-to-brain
#10
Michael C Crair, Carol A Mason
Although much is known about the regenerative capacity of retinal ganglion cells, very significant barriers remain in our ability to restore visual function following traumatic injury or disease-induced degeneration. Here we summarize our current understanding of the factors regulating axon guidance and target engagement in regenerating axons, and review the state of the field of neural regeneration, focusing on the visual system and highlighting studies using other model systems that can inform analysis of visual system regeneration...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27797960/senescence-associated-secretory-phenotype-contributes-to-pathological-angiogenesis-in-retinopathy
#11
Malika Oubaha, Khalil Miloudi, Agnieszka Dejda, Vera Guber, Gaëlle Mawambo, Marie-Anne Germain, Guillaume Bourdel, Natalija Popovic, Flavio A Rezende, Randal J Kaufman, Frédérick A Mallette, Przemyslaw Sapieha
Pathological angiogenesis is the hallmark of diseases such as cancer and retinopathies. Although tissue hypoxia and inflammation are recognized as central drivers of vessel growth, relatively little is known about the process that bridges the two. In a mouse model of ischemic retinopathy, we found that hypoxic regions of the retina showed only modest rates of apoptosis despite severely compromised metabolic supply. Using transcriptomic analysis and inducible loss-of-function genetics, we demonstrated that ischemic retinal cells instead engage the endoplasmic reticulum stress inositol-requiring enzyme 1α (IRE1α) pathway that, through its endoribonuclease activity, induces a state of senescence in which cells adopt a senescence-associated secretory phenotype (SASP)...
October 26, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27784628/advances-in-bone-marrow-stem-cell-therapy-for-retinal-dysfunction
#12
REVIEW
Susanna S Park, Elad Moisseiev, Gerhard Bauer, Johnathon D Anderson, Maria B Grant, Azhar Zam, Robert J Zawadzki, John S Werner, Jan A Nolta
The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue...
October 23, 2016: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/27759082/jak-stat-signaling-regulates-the-proliferation-and-neurogenic-potential-of-m%C3%A3-ller-glia-derived-progenitor-cells-in-the-avian-retina
#13
Levi Todd, Natalie Squires, Lilianna Suarez, Andy J Fischer
Müller glia are capable of de-differentiating and proliferating to become Müller glia-derived progenitor cells (MGPCs) with the ability to regenerate retinal neurons. One of the cell-signaling pathways that drives the reprogramming of Müller glia into MGPCs in the zebrafish retina is the Jak/Stat-pathway. However, nothing is known about the influence of Jak/Stat-signaling during the formation of MGPCs in the retinas of warm-blooded vertebrates. Accordingly, we examined whether Jak/Stat-signaling influences the formation of MGPCs and differentiation of progeny in the avian retina...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27743342/expression-of-soxc-transcription-factors-during-zebrafish-retinal-and-optic-nerve-regeneration
#14
Zhaoxia Mu, Shuqiang Zhang, Chunjiao He, Haitao Hou, Dong Liu, Nan Hu, Hui Xu
The SoxC transcription factors (Sox4, Sox11, and Sox12) play important roles in the development of the vertebrate eye and retina. However, their expression and function during retinal and optic nerve regeneration remain elusive. In this study, we investigated the expression and possible functions of the SoxC genes after retinal and optic nerve injury in adult zebrafish. We found that among the five SoxC members, Sox11b was strongly induced in BrdU-positive cells in the inner nuclear layer (INL) after retinal injury, and morpholino-mediated Sox11b-knockdown significantly reduced the number of proliferating cells in the INL at 4 days post-injury...
October 14, 2016: Neuroscience Bulletin
https://www.readbyqxmd.com/read/27734405/analysis-of-ccn-protein-expression-and-activities-in-vasoproliferative-retinopathies
#15
Sangmi Lee, Menna Elaskandrany, Afruja Ahad, Brahim Chaqour
The retina is a complex neurovascular structure that conveys light/visual image through the optic nerve to the visual cortex of the brain. Neuronal and vascular activities in the retina are physically and functionally intertwined, and vascular alterations are consequential to the proper function of the entire visual system. In particular, alteration of the structure and barrier function of the retinal vasculature is commonly associated with the development of vasoproliferative ischemic retinopathy, a set of clinically well-defined chronic ocular microvascular complications causing blindness in all age groups...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27699411/rapid-dynamic-activation-of-m%C3%A3-ller-glial-stem-cell-responses-in-zebrafish
#16
Christopher J Sifuentes, Jung-Woong Kim, Anand Swaroop, Pamela A Raymond
Purpose: Zebrafish neurons regenerate from Müller glia following retinal lesions. Genes and signaling pathways important for retinal regeneration in zebrafish have been described, but our understanding of how Müller glial stem cell properties are regulated is incomplete. Mammalian Müller glia possess a latent neurogenic capacity that might be enhanced in regenerative therapies to treat degenerative retinal diseases. Methods: To identify transcriptional changes associated with stem cell properties in zebrafish Müller glia, we performed a comparative transcriptome analysis from isolated cells at 8 and 16 hours following an acute photic lesion, prior to the asymmetric division that produces retinal progenitors...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27671232/klf4-knockdown-attenuates-tbi-induced-neuronal-damage-through-p53-and-jak-stat3-signaling
#17
Da-Ming Cui, Tao Zeng, Jie Ren, Ke Wang, Yi Jin, Lin Zhou, Liang Gao
AIMS: Traumatic brain injury (TBI) is induced by complex primary and secondary mechanisms that give rise to cell death, inflammation, and neurological dysfunction. Understanding the mechanisms that drive neurological damage as well as those that promote repair can guide the development of therapeutic drugs for TBI. Kruppel-like factor 4 (KLF4) has been reported to negatively regulate axon regeneration of injured retinal ganglion cells (RGCs) through inhibition of JAK-STAT3 signaling. However, the role of KLF4 in TBI remains unreported...
September 27, 2016: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27664291/gene-therapy-and-stem-cell-transplantation-in-retinal-disease-the-new-frontier
#18
Robert E MacLaren, Jean Bennett, Steven D Schwartz
Gene and cell therapies have the potential to prevent, halt, or reverse diseases of the retina in patients with currently incurable blinding conditions. Over the past 2 decades, major advances in our understanding of the pathobiologic basis of retinal diseases, coupled with growth of gene transfer and cell transplantation biotechnologies, have created optimism that previously blinding retinal conditions may be treatable. It is now possible to deliver cloned genes safely and stably to specific retinal cell types in humans...
October 2016: Ophthalmology
https://www.readbyqxmd.com/read/27661854/evaluation-of-nonperfused-retinal-vessels-in-ischemic-retinopathy
#19
Michael B Powner, Dawn A Sim, Meidong Zhu, João Nobre-Cardoso, Ryan Jones, Adil Syed, Andrew A Chang, Pearse A Keane, Adnan Tufail, Catherine A Egan, Marcus Fruttiger
Purpose: Retinal ischemia has been traditionally assessed by fluorescein angiography, visualizing perfused vessels. However, this method does not provide any information about nonperfused vessels, and although it is often assumed that vessels in ischemic areas regress, we know little about how nonperfused retinal vessels change over time. Here, we aim to learn more about the long-term fate of nonperfused vessels in the retinal vasculature. Methods: Optical coherence tomography (OCT) was used to visualize perfusion as well as structural properties of the retinal vasculature in patients suffering from retinal vascular occlusions...
September 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27640672/turning-the-fate-of-reprogramming-cells-from-retinal-disorder-to-regeneration-by-pax6-in-newts
#20
Martin Miguel Casco-Robles, Md Rafiqul Islam, Wataru Inami, Hibiki Vincent Tanaka, Ailidana Kunahong, Hirofumi Yasumuro, Shiori Hanzawa, Roman Martin Casco-Robles, Fubito Toyama, Fumiaki Maruo, Chikafumi Chiba
The newt, a urodele amphibian, has an outstanding ability- even as an adult -to regenerate a functional retina through reprogramming and proliferation of the retinal pigment epithelium (RPE) cells, even though the neural retina is completely removed from the eye by surgery. It remains unknown how the newt invented such a superior mechanism. Here we show that disability of RPE cells to regenerate the retina brings about a symptom of proliferative vitreoretinopathy (PVR), even in the newt. When Pax6, a transcription factor that is re-expressed in reprogramming RPE cells, is knocked down in transgenic juvenile newts, these cells proliferate but eventually give rise to cell aggregates that uniformly express alpha smooth muscle actin, Vimentin and N-cadherin, the markers of myofibroblasts which are a major component of the sub-/epi-retinal membranes in PVR...
2016: Scientific Reports
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