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Retinal regeneration

Yingqian Peng, Edouard Baulier, Yifeng Ke, Alejandra Young, Novruz B Ahmedli, Steven D Schwartz, Debora B Farber
Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions...
2018: PloS One
Adam DeBusk, Mark L Moster
PURPOSE OF REVIEW: Highlight some of the recent advances in gene therapy and gene modification for optic nerve disease to promote axon regeneration, neuroprotection, and increased visual functioning. RECENT FINDINGS: Visual loss secondary to optic nerve damage occurs in numerous ophthalmologic and neurologic conditions. Damaged retinal ganglion cells (RGCs) do not regenerate once they undergo apoptosis after injury. Gene therapy has been studied to replace gene mutations in disorders affecting the optic nerve as well as to alter genes responsible for suppressing or activating pathways of optic nerve growth and regeneration...
March 13, 2018: Current Opinion in Ophthalmology
Massimo Dal Monte, Maurizio Cammalleri, Filippo Locri, Rosario Amato, Stefania Marsili, Dario Rusciano, Paola Bagnoli
Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration...
March 8, 2018: Nutrients
Xu-Xu Liu, Wei-Dong Liu, Lei Wang, Bin Zhu, Xiao Shi, Zi-Xuan Peng, He-Cheng Zhu, Xing-Dong Liu, Mei-Zuo Zhong, Dan Xie, Mu-Sheng Zeng, Cai-Ping Ren
The identification and use of molecular biomarkers have greatly improved the diagnosis and treatment of malignant tumors. However, a much deeper understanding of oncogenic proteins is needed for the benefit to cancer patients. The lipid raft marker proteins, flotillin-1 and flotillin-2, were first found in goldfish retinal ganglion cells during axon regeneration. They have since been found in a variety of cells, mainly on the inner surface of cell membranes, and not only act as a skeleton to provide a platform for protein-protein interactions, but also are involved in signal transduction, nerve regeneration, endocytosis, and lymphocyte activation...
2018: Journal of Zhejiang University. Science. B
Valeria Chichagova, Dean Hallam, Joseph Collin, Darin Zerti, Birthe Dorgau, Majed Felemban, Majlinda Lako, David H Steel
Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process...
March 5, 2018: Eye
Hai-Tao Hou, Jin-Yang Lv, Zhi-Qiang Zhang, Ying Lu, Cui-Ping Zhou, Tian-Qiu Zhou, Shu-Qiang Zhang, Hui Xu
In vivo electroporation of morpholinos (MOs) into the retina of adult zebrafish is an efficient method to study gene function related to retinal disease and regeneration. However, the currently reported methods are complicated with low MO transfer efficiency and high probability to cause collateral damage. The present study was aimed to optimize the existing MO electroporation methods. Two major changes were made to MO electroporation procedure in zebrafish retina. One was to coat the inner side of the electrode with ultrasonic gel...
February 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Lei Li, Li-Ping Chen, Qing-Huai Liu
AIM: To explore the effect of the Notch signaling pathway on retinal ganglion cells (RGCs) and optic nerve in rats with acute ocular hypertension (OH). METHODS: Totally 48 Sprague-Dawley (SD) rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 µL phosphate buffered solution (PBS) and another group of OH rats received a single intravitreal injection of 10 µmol/L γ-secretase inhibitor (DAPT)...
2018: International Journal of Ophthalmology
Kei-Ichi Nakashima, Keiichiro Iwao, Toshihiro Inoue, Akira Haga, Takayuki Tsutsumi, Miyuki Inoue Mochita, Tomokazu Fujimoto, Hidenobu Tanihara
Among candidate neuroprotective agents, adenosine is thought to be a possible treatment for central nervous system disorders. Adenosine elicits biological effects through four G protein-coupled receptors (A1 , A2A , A2B , and A3 ). The A2A and A2B receptors stimulate adenylyl cyclase (AC) and increase cyclic adenosine monophosphate (cAMP) levels, whereas A1 and A3 receptors inhibit AC and decrease cAMP levels. Several studies have investigated the effects of adenosine receptors (AdoRs) in glaucoma, because modulation of A1 , A2A , or A3 receptor regulates intraocular pressure...
February 24, 2018: Experimental Eye Research
Ling-Ping Cen, Tsz Kin Ng, Jia-Jian Liang, Xi Zhuang, Xiaowu Yao, Gary Hin-Fai Yam, Haoyu Chen, Herman S Cheung, Mingzhi Zhang, Chi Pui Pang
Optic neuropathies are the leading cause of irreversible blindness and visual impairment in the developed countries, affecting more than 80 million people worldwide. While most optic neuropathies have no effective treatment, there is intensive research on retinal ganglion cell (RGC) protection and axon regeneration. We previously demonstrated potential of human periodontal ligament-derived stem cells (PDLSCs) for retinal cell replacement. Here, we report the neuroprotective effect of human PDLSCs to ameliorate RGC degeneration and promote axonal regeneration after optic nerve crush (ONC) injury...
February 24, 2018: Stem Cells
Jiaxing Wang, Ying Li, Rebecca King, Felix L Struebing, Eldon E Geisert
Purpose: The present study is designed to identify the influences of genetic background on optic nerve regeneration using the two parental strains (C57BL/6J and DBA/2J) and seven BXD recombinant inbred mouse strains. Methods: To study regeneration in the optic nerve, Pten was knocked down in the retinal ganglion cells using adenoassociated virus (AAV) delivery of shRNA, and a mild inflammatory response was induced with an intravitreal injection of zymosan with CPT-cAMP...
2018: Molecular Vision
Thomas Fleming, Carlos G Martinez-Moreno, Martha Carranza, Maricela Luna, Steve Harvey, Carlos Arámburo
There is increasing evidence that suggests a possible role for GH in retinal development and synaptogenesis. While our previous studies have focused largely on embryonic retinal ganglion cells (RGCs), our current study demonstrates that GH has a synaptogenic effect in retinal primary cell cultures, increasing the abundance of both pre- (SNAP25) and post- (PSD95) synaptic proteins. In the neonatal chick, kainate (KA) treatment was found to damage retinal synapses and abrogate GH expression. In response to damage, an increase in Cy3-GH internalization into RGCs was observed when administered shortly before or after damage...
February 15, 2018: General and Comparative Endocrinology
Songqi Gao, Shirin Kahremany, Jianye Zhang, Beata Jastrzebska, Janice Querubin, Simon M Petersen-Jones, Krzysztof Palczewski
The retinoid (visual) cycle consists of a series of biochemical reactions needed to regenerate the visual chromophore, 11-cis-retinal and sustain vision. Genetic or environmental factors affecting chromophore production can lead to blindness. Using animal models that mimic human retinal diseases, we previously demonstrated that mechanism-based pharmacological interventions can maintain vision in otherwise incurable genetic diseases of the retina. Here, we report that after 9-cis-retinal administration to lecithin:retinol acyltransferase-deficient (Lrat-/-) mice, the drug was rapidly absorbed and then cleared within 1-2 h...
February 16, 2018: Molecular Pharmacology
Yong Sheng Edgar Tan, Pu Jiang Shi, Chang-J Choo, Augustinus Laude, Wai Yee Yeong
The biological, structural and functional configuration of Bruch's membrane (BM) is significantly relevant to age-related macular degeneration (AMD) and other chorioretinal diseases, and AMD is one of the leading causes of blindness in the elderly worldwide. The configuration may worsen along with the ageing of retinal pigment epithelium and BM that finally leads to AMD. Thus, the scaffold-based tissue-engineered retina provides an innovative alternative for retinal tissue repair. The cell and material requirements for retinal repair are discussed including cell sheet engineering, decellularised membrane and tissue-engineered membranes...
February 16, 2018: British Journal of Ophthalmology
Zheng-Ru Huang, Hai-Ying Chen, Zi-Zhong Hu, Ping Xie, Qing-Huai Liu
The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog (PTEN) enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated (Y444F) AAV2 vector to efficiently express a short hairpin RNA (shRNA) for silencing PTEN expression in retinal ganglion cells...
January 2018: Neural Regeneration Research
Armando L Garcia, Adanna Udeh, Karthik Kalahasty, Abigail S Hackam
The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy...
January 2018: Neural Regeneration Research
Sonja Mertsch, Katrin Schlicht, Harutyun Melkonyan, Stefan Schlatt, Solon Thanos
BACKGROUND: Retinal ganglion cells (RGCs) of mammals lose the ability to regenerate injured axons during postnatal maturation, but little is known about the underlying molecular mechanisms. OBJECTIVE: It remains of particular importance to understand the mechanisms of axonal regeneration to develop new therapeutic approaches for nerve injuries. METHODS: Retinas from newborn to adult monkeys (Callithrix jacchus)1 were obtained immediately after death and cultured in vitro...
2018: Restorative Neurology and Neuroscience
Seoh Wei Teh, Pooi Ling Mok, Munirah Abd Rashid, Mae-Lynn Catherine Bastion, Normala Ibrahim, Akon Higuchi, Kadarkarai Murugan, Rajan Mariappan, Suresh Kumar Subbiah
Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area...
February 13, 2018: International Journal of Molecular Sciences
Chi Sun, Carlos Galicia, Deborah L Stenkamp
BACKGROUND: The purpose of this study was to identify transcripts of retinal rod photoreceptors of the zebrafish. The zebrafish is an important animal model for vision science due to rapid and tractable development, persistent neurogenesis of rods throughout the lifespan, and capacity for functional retinal regeneration. RESULTS: Zebrafish rods, and non-rod retinal cells of the xops:eGFP transgenic line, were separated by cell dissociation and fluorescence-activated cell sorting (FACS), followed by RNA-seq...
February 8, 2018: BMC Genomics
Chenying Guo, Kin-Sang Cho, Yingqian Li, Kissauo Tchedre, Christian Antolik, Jie Ma, Justin Chew, Tor Paaske Utheim, Xizhong A Huang, Honghua Yu, Muhammad Taimur A Malik, Nada Anzak, Dong Feng Chen
Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth...
February 1, 2018: Scientific Reports
Fairouz Elsaeidi, Peter Macpherson, Elizabeth A Mills, Jonathan Jui, John G Flannery, Daniel Goldman
Muller glial cells (MG) in the zebrafish retina respond to injury by acquiring retinal stem cell characteristics. Thousands of gene expression changes are associated with this event. Key among these changes are the induction of Ascl1a and Lin28a, two reprogramming factors whose expression is necessary for retina regeneration. Whether these factors are sufficient to drive MG proliferation and subsequent neuronal-fate specification remains unknown. To test this, we conditionally expressed Ascl1a and Lin28a in the uninjured retina of male and female fish...
January 29, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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