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Retinal regeneration

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https://www.readbyqxmd.com/read/28548249/m%C3%A3-ller-glial-cell-reactivation-in-xenopus-models-of-retinal-degeneration
#1
Rahul Langhe, Albert Chesneau, Gabriele Colozza, Magdalena Hidalgo, Divya Ail, Morgane Locker, Muriel Perron
A striking aspect of tissue regeneration is its uneven distribution among different animal classes, both in terms of modalities and efficiency. The retina does not escape the rule, exhibiting extraordinary self-repair properties in anamniote species but extremely limited ones in mammals. Among cellular sources prone to contribute to retinal regeneration are Müller glial cells, which in teleosts have been known for a decade to re-acquire a stem/progenitor state and regenerate retinal neurons following injury...
May 26, 2017: Glia
https://www.readbyqxmd.com/read/28539612/the-role-of-retinol-dehydrogenase-10-in-the-cone-visual-cycle
#2
Yunlu Xue, Shinya Sato, David Razafsky, Bhubanananda Sahu, Susan Q Shen, Chloe Potter, Lisa L Sandell, Joseph C Corbo, Krzysztof Palczewski, Akiko Maeda, Didier Hodzic, Vladimir J Kefalov
Pigment regeneration is critical for the function of cone photoreceptors in bright and rapidly-changing light conditions. This process is facilitated by the recently-characterized retina visual cycle, in which Müller cells recycle spent all-trans-retinol visual chromophore back to 11-cis-retinol. This 11-cis-retinol is oxidized selectively in cones to the 11-cis-retinal used for pigment regeneration. However, the enzyme responsible for the oxidation of 11-cis-retinol remains unknown. Here, we sought to determine whether retinol dehydrogenase 10 (RDH10), upregulated in rod/cone hybrid retinas and expressed abundantly in Müller cells, is the enzyme that drives this reaction...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539419/microglia-are-irrelevant-for-neuronal-degeneration-and-axon-regeneration-after-acute-injury
#3
Alexander M Hilla, Heike Diekmann, Dietmar Fischer
The role of microglia in de- and regenerative processes after damage of the nervous system still remains ambiguous, partially due to the paucity of appropriate investigative methods. Here, we show that treatment with the pharmacological colony stimulating factor 1 receptor inhibitor PLX5622 specifically eliminated microglia in murine retinae and optic nerves. Interestingly, time course and extent of retinal ganglion cell (RGC) degeneration after optic nerve crush remained unaffected upon microglia depletion, although remnants of pre-labeled apoptotic RGCs were not cleared from the retina in these animals...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28536395/cellular-and-molecular-preconditions-for-retinal-pigment-epithelium-rpe-natural-reprogramming-during-retinal-regeneration-in-urodela
#4
REVIEW
Eleonora N Grigoryan, Yuliya V Markitantova
Many regeneration processes in animals are based on the phenomenon of cell reprogramming followed by proliferation and differentiation in a different specialization direction. An insight into what makes natural (in vivo) cell reprogramming possible can help to solve a number of biomedical problems. In particular, the first problem is to reveal the intrinsic properties of the cells that are necessary and sufficient for reprogramming; the second, to evaluate these properties and, on this basis, to reveal potential endogenous sources for cell substitution in damaged tissues; and the third, to use the acquired data for developing approaches to in vitro cell reprogramming in order to obtain a cell reserve for damaged tissue repair...
December 1, 2016: Biomedicines
https://www.readbyqxmd.com/read/28536368/implications-of-a-multi-step-trigger-of-retinal-regeneration-in-the-adult-newt
#5
Hirofumi Yasumuro, Keisuke Sakurai, Fubito Toyama, Fumiaki Maruo, Chikafumi Chiba
The newt is an amazing four-limbed vertebrate that can regenerate various body parts including the retina. In this animal, when the neural retina (NR) is removed from the eye by surgery (retinectomy), both the NR and the retinal pigment epithelium (RPE) eventually regenerate through the process of reprogramming and proliferation of RPE cells. Thus far, we have pursued the onset mechanism of adult newt retinal regeneration. In this study, using an in vitro system, we found that both mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK and β-catenin were involved in cell cycle re-entry of RPE cells...
May 20, 2017: Biomedicines
https://www.readbyqxmd.com/read/28487362/complex-binding-pathways-determine-the-regeneration-of-mammalian-green-cone-opsin-with-a-locked-retinal-analogue
#6
Nathan S Alexander, Kota Katayama, Wenyu Sun, David Salom, Sahil Gulati, Jianye Zhang, Muneto Mogi, Krzysztof Palczewski, Beata Jastrzebska
Phototransduction is initiated when the absorption of light converts the 11-cis-retinal chromophore to its all-trans configuration in both rod and cone vertebrate photoreceptors. To sustain vision, 11-cis-retinal is continuously regenerated from its all-trans conformation through a series of enzymatic steps comprising the visual or retinoid cycle. Abnormalities in this cycle can compromise vision because of the diminished supply of 11-cis-retinal and the accumulation of toxic, constitutively active opsin. As shown previously for rod cells, attenuation of constitutively active opsin can be achieved with the unbleachable analogue, 11-cis-6-membered ring (11-cis-6mr)-retinal, which has therapeutic effects against certain degenerative retinal diseases...
May 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28487225/structural-and-functional-alterations-associated-with-deutan-n94k-and-r330q-mutations-of-green-cone-opsin
#7
Sundaramoorthy Srinivasan, Miguel A Fernández-Sampedro, Eva Ramon, Pere Garriga
Deuteranopia is an X-linked congenital dichromatic condition in which single point mutations in green cone opsin lead to defective non-functional cone photoreceptor cells. Green cone opsin belongs to the G protein-coupled receptor superfamily and consists of a seven transmembrane helical apoprotein covalently bound to 11-cis-retinal, by means of a protonated Schiff base linkage, in its inactive dark state. Several point mutations in green cone opsin have been reported to cause deuteranopia, but the structural details underlying the molecular mechanisms behind the malfunction of mutated opsins have not been clearly established...
May 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28486987/progress-of-stem-progenitor-cell-based-therapy-for-retinal-degeneration
#8
REVIEW
Zhimin Tang, Yi Zhang, Yuyao Wang, Dandan Zhang, Bingqiao Shen, Min Luo, Ping Gu
Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE...
May 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28480968/the-influence-of-raav2-mediated-sox2-delivery-into-neonatal-and-adult-human-rpe-cells-a-comparative-study
#9
Razie Ezati, Azadeh Etemadzadeh, Zahra-Soheila Soheili, Shahram Samiei, Ehsan Ranaei Pirmardan, Malihe Davari, Hoda Shams Najafabadi
Cell replacement is a promising therapy for degenerative diseases like age-related macular degeneration (AMD). Since the human retina lacks regeneration capacity, much attention has been directed towards persuading for cells that can differentiate into retinal neurons. In this report we have investigated reprogramming of the human RPE cells and concerned the effect of donor age on the cellular fate as a critical determinant in reprograming competence. We evaluated the effect of SOX2 over-expression in human neonatal and adult RPE cells in cultures...
May 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28476927/rational-tuning-of-visual-cycle-modulator-pharmacodynamics
#10
Philip D Kiser, Jianye Zhang, Mohsen Badiee, Junzo Kinoshita, Neal S Peachey, Gregory P Tochtrop, Krzysztof Palczewski
Modulators of the visual cycle have been developed for treatment of various retinal disorders. These agents were designed to inhibit retinoid isomerase (RPE65), the rate-limiting enzyme of the visual cycle, based on the idea that attenuation of visual pigment regeneration could reduce formation of toxic retinal conjugates. Certain of these agents that contain primary amine groups also can also reversibly form retinaldehyde-Schiff base adducts, which contributes to their retinal protective activity. Direct inhibition of RPE65 as a therapeutic strategy is complicated by adverse effects resulting from slowed chromophore regeneration whereas effective retinal sequestration can require high drug doses with potential off-target effects...
May 5, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28469643/impacts-of-the-retinal-environment-and-photoreceptor-type-on-functional-regeneration
#11
REVIEW
Michèle G DuVal, W Ted Allison
Retinal regeneration is a promising central nervous system (CNS) target amongst the various stem cell therapy pursuits, due to its accessibility for manipulation and its disposition towards longitudinal monitoring of treatment safety and efficacy. We offer our perspective on current hurdles towards functional regeneration of cone photoreceptors. Cones are key: For patients suffering vision loss, cone photoreceptors are a required cellular component to restoring daytime vision, colour vision, and high acuity vision...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28445734/opposing-actions-of-fgf8a-on-notch-signaling-distinguish-two-muller-glial-cell-populations-that-contribute-to-retina-growth-and-regeneration
#12
Jin Wan, Daniel Goldman
The teleost retina grows throughout life and exhibits a robust regenerative response following injury. Critical to both these events are Muller glia (or, Muller glial cells; MGs), which produce progenitors for retinal growth and repair. We report that Fgf8a may be an MG niche factor that acts through Notch signaling to regulate spontaneous and injury-dependent MG proliferation. Remarkably, forced Fgf8a expression inhibits Notch signaling and stimulates MG proliferation in young tissue but increases Notch signaling and suppresses MG proliferation in older tissue...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28440470/proliferation-and-differentiation-of-direct-co%C3%A2-culture-of-bone-marrow-mesenchymal-stem-cells-and-pigmented-cells-from-the-ciliary-margin
#13
Yan Li, Xinzheng He, Jun Li, Fangfang Ni, Qingqing Sun, Yan Zhou
Damage of retinal ganglion cells (RGCs) is the major consequence of glaucoma and regeneration of RGCs is extremely difficult once the damage has occurred. Retinal stem cells (RSCs) are considered an ideal choice for RGC regeneration. Pigmented cells from the ciliary margin (PCMs) have great retinal differentiation potential and may be an ideal RSC candidate. However, the ciliary margin is too small, so the number of cells that can be obtained is limited. Bone marrow‑derived mesenchymal stem cells (BMMSCs) are another type of stem cell that have been previously investigated for RGC regeneration...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28426967/an-intrinsic-epigenetic-barrier-for-functional-axon-regeneration
#14
Yi-Lan Weng, Ran An, Jessica Cassin, Jessica Joseph, Ruifa Mi, Chen Wang, Chun Zhong, Seung-Gi Jin, Gerd P Pfeifer, Alfonso Bellacosa, Xinzhong Dong, Ahmet Hoke, Zhigang He, Hongjun Song, Guo-Li Ming
Mature neurons in the adult peripheral nervous system can effectively switch from a dormant state with little axonal growth to robust axon regeneration upon injury. The mechanisms by which injury unlocks mature neurons' intrinsic axonal growth competence are not well understood. Here, we show that peripheral sciatic nerve lesion in adult mice leads to elevated levels of Tet3 and 5-hydroxylmethylcytosine in dorsal root ganglion (DRG) neurons. Functionally, Tet3 is required for robust axon regeneration of DRG neurons and behavioral recovery...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28416692/immunomodulation-accelerated-neuronal-regeneration-following-selective-rod-photoreceptor-cell-ablation-in-the-zebrafish-retina
#15
David T White, Sumitra Sengupta, Meera T Saxena, Qingguo Xu, Justin Hanes, Ding Ding, Hongkai Ji, Jeff S Mumm
Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28381675/alternative-formation-of-red-shifted-channelrhodopsins-noncovalent-incorporation-with-retinal-based-enamine-type-schiff-bases-and-mutated-channelopsin
#16
Takashi Okitsu, Take Matsuyama, Takahiro Yamashita, Toru Ishizuka, Hiromu Yawo, Yasushi Imamoto, Yoshinori Shichida, Akimori Wada
Red-shifted channelrhodopsins (ChRs) are attractive for optogenetic tools. We developed a new type of red-shifted ChRs that utilized noncovalent incorporation of retinal and 3,4-dehydroretinal-based enamine-type Schiff bases and mutated channelopsin, C1C2-K296G. These ChRs exhibited absorption maxima that were shifted 10-30 nm toward longer wavelengths than that of C1C2-ChR regenerated with all-trans-retinal.
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28371543/upregulation-of-matrix-metalloproteinase-triggers-transdifferentiation-of-retinal-pigmented-epithelial-cells-in-xenopus-laevis-a-link-between-inflammatory-response-and-regeneration
#17
Hanako Naitoh, Yukari Suganuma, Yoko Ueda, Takahiko Sato, Yosuke Hiramuki, Atsuko Fujisawa-Sehara, Shigeru Taketani, Masasuke Araki
In adult Xenopus eyes, when the whole retina is removed, retinal pigmented epithelial (RPE) cells become activated to be retinal stem cells and regenerate the whole retina. In the present study, using a tissue culture model, we examined whether upregulation of matrix metalloproteinases (Mmps) triggers retinal regeneration. Soon after retinal removal, Xmmp9 and Xmmp18 were strongly upregulated in the tissues of the RPE and the choroid. In the culture, Mmp expression in the RPE cells corresponded with their migration from the choroid...
April 2, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28367115/identification-of-mesencephalic-astrocyte-derived-neurotrophic-factor-as-a-novel-neuroprotective-factor-for-retinal-ganglion-cells
#18
Feng-Juan Gao, Ji-Hong Wu, Ting-Ting Li, Shan-Shan Du, Qiang Wu
Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly discovered secreted neurotrophic factor, has been proven to not only protect dopaminergic neurons and other cell types but also regulate neuroinflammation and the immune response to promote tissue repair and regeneration. However, to date, there is no information regarding the relationship between MANF and retinal ganglion cells (RGCs) in the eye. In the current study, we first determined the expression of MANF in the retina and vitreous. Then, we examined the effect of MANF on RGCs using both in vivo and in vitro models and simultaneously explored the underlying neuroprotective mechanisms of MANF...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28365209/special-commentary-early-clinical-development-of-cell-replacement-therapy-considerations-for-the-national-eye-institute-audacious-goals-initiative
#19
REVIEW
Leonard A Levin, Joan W Miller, Donald J Zack, Martin Friedlander, Lois E H Smith
The National Eye Institute launched the Audacious Goals Initiative (AGI) in 2013 with the aim "to restore vision through the regeneration of neurons and neural connections in the eye and visual system." An AGI Town Hall held at the Association for Research in Vision and Ophthalmology Annual Meeting in 2016 brought together basic, translational, and clinical scientists to address the clinical implications of the AGI, with a particular emphasis on diseases amenable to regenerative medicine and strategies to deal with barriers to progess...
March 29, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28359344/the-retina-visual-cycle-is-driven-by-cis-retinol-oxidation-in-the-outer-segments-of-cones
#20
Shinya Sato, Rikard Frederiksen, M Carter Cornwall, Vladimir J Kefalov
Vertebrate rod and cone photoreceptors require continuous supply of chromophore for regenerating their visual pigments after photoactivation. Cones, which mediate our daytime vision, demand a particularly rapid supply of 11-cis retinal chromophore in order to maintain their function in bright light. An important contribution to this process is thought to be the chromophore precursor 11-cis retinol, which is supplied to cones from Müller cells in the retina and subsequently oxidized to 11-cis retinal as part of the retina visual cycle...
January 2017: Visual Neuroscience
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