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Retinal regeneration

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https://www.readbyqxmd.com/read/28096191/allosteric-modulation-of-the-substrate-specificity-of-acyl-coa-wax-alcohol-acyltransferase-2-awat2
#1
Jason M Arne, Made Airanthi K Widjaja-Adhi, Taylor Hughes, Kevin W Huynh, Josie A Silvaroli, Sylwia Chelstowska, Vera Y Moiseenkova-Bell, Marcin Golczak
The esterification of alcohols with fatty acids is a universal mechanism to form inert storage forms of sterols, di- and triacylglycerols, and retinoids. In ocular tissues, formation of retinyl esters is an essential step in the enzymatic regeneration of the visual chromophore (11-cis-retinal). Acyl-CoA wax alcohol acyltransferase 2 (AWAT2), also known as multifunctional O-acyltransferase (MFAT), is an integral membrane enzyme with a broad substrate specificity that has been shown to preferentially esterify 11-cis-retinol and thus contribute to formation of readily available pool of cis retinoids in the eye...
January 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28049891/development-of-cellular-and-tissue-based-products-for-retinal-regenerative-medicine
#2
Fumitaka Osakada
 Since the discovery of induced pluripotent stem cells (iPSCs) generation, much progress has been made in the fields of medical and pharmaceutical research, such as cell transplantation therapy. We have generated retinal cells and tissues, including retinal pigment epithelia (RPE), from human iPSCs. The ability to produce iPSCs from patients allows for autologous transplantation without causing immune rejection. The autologous transplantation of iPSC-derived retinal pigment epithelial sheets to a patient with age-related macular degeneration was carried out in Japan in 2014 as a first-in-human clinical study...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28049831/mobile-zinc-increases-rapidly-in-the-retina-after-optic-nerve-injury-and-regulates-ganglion-cell-survival-and-optic-nerve-regeneration
#3
Yiqing Li, Lukas Andereggen, Kenya Yuki, Kumiko Omura, Yuqin Yin, Hui-Ya Gilbert, Burcu Erdogan, Maria S Asdourian, Christine Shrock, Silmara de Lima, Ulf-Peter Apfel, Yehong Zhuo, Michal Hershfinkel, Stephen J Lippard, Paul A Rosenberg, Larry Benowitz
Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn(2+)) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn(2+) increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28041994/a-dominant-mutation-in-rpe65-d477g-delays-dark-adaptation-and-disturbs-the-visual-cycle-in-the-mutant-knock-in-mice
#4
Younghwa Shin, Gennadiy Moiseyev, Dibyendu Chakraborty, Jian-Xing Ma
RPE65 is an indispensable component of the retinoid visual cycle in vertebrates, through which the visual chromophore 11-cis-retinal (11-cis-RAL) is generated to maintain normal vision. Various blinding conditions in humans, such as Leber congenital amaurosis and retinitis pigmentosa (RP), are attributed to either homozygous or compound heterozygous mutations in RPE65. Herein, we investigated D477G missense mutation, an unprecedented dominant-acting mutation of RPE65 identified in patients with autosomal dominant RP...
December 30, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/28029073/exploring-optic-nerve-axon-regeneration
#5
Hong-Jiang Li, Zhao-Liang Sun, Xi-Tao Yang, Liang Zhu, Dong-Fu Feng
Traumatic optic nerve (ON) injury is a leading cause of irreversible visual impairment worldwide. To date, neither pharmacological nor surgical interventions are sufficient to halt or reverse the progression of visual loss. Axon regeneration is critical for functional recovery of vision following ON injury. After ON injury, retinal ganglion cells (RGCs) axons usually fail to regrow and instead die back, leading to the death of the RGCs and subsequently causing the functional loss of vision. However, the detailed molecular mechanisms underlying axon regeneration after ON injury remain poorly understood...
December 27, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/28017835/aav-mediated-transfer-of-rhoa-shrna-and-cntf-promotes-retinal-ganglion-cell-survival-and-axon-regeneration
#6
Ling-Ping Cen, Jia-Jian Liang, Jian-Huan Chen, Alan R Harvey, Tsz Kin Ng, Mingzhi Zhang, Chi Pui Pang, Qi Cui, You-Ming Fan
The aim of the present study was to determine whether adeno-associated viral vector (AAV) mediated transfer of ciliary neurotrophic factor (CNTF) and RhoA shRNA has additive effects on promoting the survival and axon regeneration of retinal ganglion cells (RGCs) after optic nerve crush (ONC). Silencing effects of AAV-RhoA shRNA were confirmed by examining neurite outgrowth in PC12 cells, and by quantifying RhoA expression levels with western blotting. Young adult Fischer rats received an intravitreal injection of (i) saline, (ii) AAV green fluorescent protein (GFP), (iii) AAV-CNTF, (iv) AAV-RhoA shRNA, or (v) a combination of both AAV-CNTF and AAV-RhoA shRNA...
December 23, 2016: Neuroscience
https://www.readbyqxmd.com/read/28011153/wnt-signaling-promotes-axonal-regeneration-following-optic-nerve-injury-in-the-mouse
#7
Amit K Patel, Kevin K Park, Abigail S Hackam
Adult mammalian CNS axons generally do not regenerate, creating an obstacle to effective repair and recovery after neuronal injury. The canonical Wnt/β-catenin signaling pathway is an essential signal transduction cascade that regulates axon growth and neurite extension in the developing mammalian embryo. In this study, we investigated whether a Wnt/β-catenin signaling activator could be repurposed to induce regeneration in the adult CNS after axonal injury. We used a retinal ganglion cell (RGC) axon crush injury model in a transgenic Wnt reporter mouse, and intravitreal injections were used to deliver Wnt3a or saline to the RGC cell bodies within the retina...
December 21, 2016: Neuroscience
https://www.readbyqxmd.com/read/28009347/an-integrin-approach-to-axon-regeneration
#8
J W Fawcett
Axon regeneration in the CNS is blocked by inhibitory molecules in the environment and by a developmental loss of regenerative potential in CNS axons. Axon growth is a specialized form of cell migration, and for any cell to migrate there must be an adhesion molecule at the growth tip that recognizes a ligand in the environment, and which is linked to signaling and cytoskeletal mechanisms. The reasons for this loss of regenerative ability in CNS axons are several, but important contributors are the developmental loss of integrins that recognize ligands in the mature CNS environment, and selective trafficking of integrins and other molecules to exclude them from axons and direct them to dendrites...
December 23, 2016: Eye
https://www.readbyqxmd.com/read/28009275/the-mammalian-specific-protein-armcx1-regulates-mitochondrial-transport-during-axon-regeneration
#9
Romain Cartoni, Michael W Norsworthy, Fengfeng Bei, Chen Wang, Siwei Li, Yiling Zhang, Christopher V Gabel, Thomas L Schwarz, Zhigang He
Mitochondrial transport is crucial for neuronal and axonal physiology. However, whether and how it impacts neuronal injury responses, such as neuronal survival and axon regeneration, remain largely unknown. In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition. Armcx1 overexpression enhances mitochondrial transport in adult retinal ganglion cells (RGCs)...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/28007643/synergistic-effect-of-olfactory-ensheathing-cells-and-alpha-crystallin-on-restoration-of-adult-rat-optic-nerve-injury
#10
Yan Hua Wang, Zheng Qin Yin, Yi Wang
Olfactory enshesathing cells (OECs) and α-crystallin all can promote axonal regeneration after optic nerve injury. However, their mechanisms were different. Here, we study the synergistic effect of OECs and α-crystallin on the optic nerve regeneration. α-Crystallin was injected into vitreous cavity, and OECs were transplanted to the optic nerve injury area. The regeneration length of optic nerve were measured by anterograde tracing using cholera toxin subunit B (CTB). The survival of RGCs were assessed by counting the numbers of βIII-tubulin-labeled RGCs in a retinal whole mount...
December 19, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27983731/whole-eye-transplantation-a-look-into-the-past-and-vision-for-the-future
#11
D Bourne, Y Li, C Komatsu, M R Miller, E H Davidson, L He, I A Rosner, H Tang, W Chen, M G Solari, J S Schuman, K M Washington
Blindness afflicts ~39 million people worldwide. Retinal ganglion cells are unable to regenerate, making this condition irreversible in many cases. Whole-eye transplantation (WET) provides the opportunity to replace diseased retinal ganglion cells, as well as the entire optical system and surrounding facial tissue, if necessary. Recent success in face transplantation demonstrates that this may be a promising treatment for what has been to this time an incurable condition. An animal model for WET must be established to further enhance our knowledge of nerve regeneration, immunosuppression, and technical aspects of surgery...
December 16, 2016: Eye
https://www.readbyqxmd.com/read/27933306/significant-changes-in-endogenous-retinal-gene-expression-assessed-1-year-after-a-single-intraocular-injection-of-aav-cntf-or-aav-bdnf
#12
Chrisna J LeVaillant, Anil Sharma, Jill Muhling, Lachlan Pg Wheeler, Greg S Cozens, Mats Hellström, Jennifer Rodger, Alan R Harvey
Use of viral vectors to deliver therapeutic genes to the central nervous system holds promise for the treatment of neurodegenerative diseases and neurotrauma. Adeno-associated viral (AAV) vectors encoding brain-derived neurotrophic factor (BDNF) or ciliary derived neurotrophic factor (CNTF) promote the viability and regeneration of injured adult rat retinal ganglion cells. However, these growth-inducing transgenes are driven by a constitutively active promoter, thus we examined whether long-term AAV-mediated secretion of BDNF or CNTF affected endogenous retinal gene expression...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27924617/cxcl12-sdf-1-dependent-retinal-migration-of-endogenous-bone-marrow-derived-stem-cells-improves-visual-function-after-pharmacologically-induced-retinal-degeneration
#13
Volker Enzmann, Stéphanie Lecaudé, Anna Kruschinski, Axel Vater
Mobilized bone marrow-derived stem cells (BMSC) have been discussed as an alternative strategy for endogenous repair. Thereby, different approaches for BMSC mobilization have been pursued. Herein, the role of a newly discovered oligonucleotide for retinal homing and regeneration capability of BMSCs was investigated in the sodium iodate (NaIO3) model of retinal degeneration. Mobilization was achieved in GFP-chimera with NOX-A12, a CXC-motif chemokine ligand 12 (CXCL12)/stromal cell-derived factor 1 (SDF-1)-neutralizing L-aptamer...
December 6, 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27918823/short-term-alteration-of-developmental-neural-activity-enhances-neurite-outgrowth-of-retinal-explants
#14
Meng-Jung Lee, Chuan-Chin Chiao
Purpose: It is well known that the gradual loss of axon growth ability of retinal ganglion cells (RGCs) during development is largely determined by extrinsic signals rather than being programmed intrinsically. Spontaneous retinal waves are the major neural activity during retinal development. Thus restoring the developmental environment by providing the proper neural activity may be able to help axon regeneration of RGCs. Methods: Retinal explants from P5 and P11 C57BL/6 mice were treated pharmacologically or stimulated electrically, and cultured with or without brain-derived neurotrophic factor (BDNF) on coverslips or a multielectrode array for 5 days to examine the neurite outgrowth capacity of RGCs...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27916026/role-of-cyclic-amp-in-the-eye-of-glaucoma
#15
Myoung Sup Shim, Keun-Young Kim, Won-Kyu Ju
Glaucoma is characterized by a slow and progressive degeneration of optic nerve, including retinal ganglion cell (RGC) axons in the optic nerve head (ONH), leading to visual impairment. Despite the high prevalence, the biological basis of glaucoma pathogenesis still is not yet fully understood, and the factors contributing to its progression are currently not well characterized. Intraocular pressure (IOP) is the only modifiable risk factor, and reduction of IOP is the standard treatment for glaucoma. However, lowering IOP itself is not always effective for preserving visual function in patients with primary open-angle glaucoma...
December 5, 2016: BMB Reports
https://www.readbyqxmd.com/read/27904478/neuro-rejuvenation-for-neuronal-function
#16
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
#17
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
#18
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
#19
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
#20
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
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