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glaucoma Stem cell

Pooja Teotia, Divyan A Chopra, Shashank Manohar Dravid, Matthew J Van Hook, Fang Qiu, John Morrison, Angie Rizzino, Iqbal Ahmad
Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) leads to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, i.e., the embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)...
October 6, 2016: Stem Cells
Ya-Sha Zhou, Jian Xu, Jun Peng, Ping Li, Xiao-Juan Wen, Yue Liu, Ke-Zhu Chen, Jia-Qi Liu, Ying Wang, Qing-Hua Peng
Glaucoma, the second leading cause of blindness, is an irreversible optic neuropathy. The mechanism of optic nerve injury caused by glaucoma is undefined at present. There is no effective treatment method for the injury. Stem cells have the capacity of self-renewal and differentiation. These two features have made them become the research focus on improving the injury at present. This paper reviews the application progress on different types of stem cells therapy for optic nerve injury caused by glaucoma.
2016: International Journal of Ophthalmology
Shahnaz Khan, Sandy Shen-Chi Hung, Raymond Ching-Bong Wong
PURPOSE OF REVIEW: The present review aims to provide an update of applications of induced pluripotent stem cells (iPSCs) for disease modeling, cell/gene therapy, and drug screening for optic neuropathies. RECENT FINDINGS: Degeneration of retinal ganglion cells (RGCs) is a characteristic of optic neuropathies. Human iPSCs can serve as a model to investigate disease pathology and potential repair mechanisms. In recent years, significant progress has been made in generating RGCs from iPSCs...
October 2016: Current Opinion in Organ Transplantation
Angela C Gauthier, Ji Liu
Glaucoma is the principal cause of irreversible blindness in the world. The disease leads to progressive optic nerve degeneration with a gradual loss of retinal ganglion cells. Neurodegeneration in glaucoma extends beyond the eye into the lateral geniculate nucleus and visual cortex, and the disease even shares some characteristics with other central nervous system degenerative disorders. Glaucoma destroys neurons through oxidative stress, impairment in axonal transport, neuroinflammation, and excitotoxicity...
March 2016: Yale Journal of Biology and Medicine
Nan Wu, Yi Wang, Lanbo Yang, Kin-Sang Cho
Retinal degenerative diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma result in permanent loss of retinal neurons and vision. Stem cell therapy could be a novel treatment strategy to restore visual function. In an ideal situation, a homogenous population of stem cell-derived retinal neurons with high purity is used for replacement therapy. Thus, it is crucial to elucidate the molecular mechanisms that regulate the development of retinal progenitor cells and subsequent generation of specific retinal neurons...
August 2016: Human Gene Therapy
Azadeh Doozandeh, Shahin Yazdani
Glaucoma is a degenerative optic neuropathy characterized by retinal ganglion cell (RGC) loss and visual field defects. It is known that in some glaucoma patients, death of RGCs continues despite intraocular pressure (IOP) reduction. Neuroprotection in the field of glaucoma is defined as any treatment, independent of IOP reduction, which prevents RGC death. Glutamate antagonists, ginkgo biloba extract, neurotrophic factors, antioxidants, calcium channel blockers, brimonidine, glaucoma medications with blood regulatory effect and nitric oxide synthase inhibitors are among compounds with possible neuroprotective activity in preclinical studies...
April 2016: Journal of Ophthalmic & Vision Research
Carolina Aravena, Tahir Kansu Bozkurt, Fei Yu, Anthony J Aldave
PURPOSE: To report the long-term outcomes of the Boston type I keratoprosthesis (KPro) in the management of limbal stem cell deficiency (LSCD). METHODS: Retrospective review of KPro procedures performed by a single surgeon from May 1, 2004, to January 1, 2015. RESULTS: One hundred seventy-three KPro procedures were performed in 149 eyes, including 68 in 54 eyes with LSCD. Glaucoma (48% vs. 82%, P < 0.0001) and a history of ≥2 keratoplasties (39% vs...
September 2016: Cornea
Fei Deng, Mengfei Chen, Ying Liu, Huiling Hu, Yunfan Xiong, Chaochao Xu, Yuchun Liu, Kangjun Li, Jing Zhuang, Jian Ge
PURPOSE: As an alternative and desirable approach for regenerative medicine, human induced pluripotent stem cell (hiPSC) technology raises the possibility of developing patient-tailored cell therapies to treat intractable degenerative diseases in the future. This study was undertaken to guide human Tenon's capsule fibroblasts-derived iPSCs (TiPSCs) to differentiate along the retinal ganglion cell (RGC) lineage, aiming at producing appropriate cellular material for RGC regeneration. METHODS: By mimicking RGC genesis, we deliberately administered the whole differentiation process and directed the stage-specific differentiation of human TiPSCs toward an RGC fate via manipulation of the retinal inducers (DKK1+Noggin+Lefty A) alongside master gene (Atoh7) sequentially...
2016: Molecular Vision
Wei Zhu, Oliver W Gramlich, Lauren Laboissonniere, Ankur Jain, Val C Sheffield, Jeffrey M Trimarchi, Budd A Tucker, Markus H Kuehn
Glaucoma is a common cause of vision loss or blindness and reduction of intraocular pressure (IOP) has been proven beneficial in a large fraction of glaucoma patients. The IOP is maintained by the trabecular meshwork (TM) and the elevation of IOP in open-angle glaucoma is associated with dysfunction and loss of the postmitotic cells residing within this tissue. To determine if IOP control can be maintained by replacing lost TM cells, we transplanted TM-like cells derived from induced pluripotent stem cells into the anterior chamber of a transgenic mouse model of glaucoma...
June 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
Ben Mead, Ann Logan, Martin Berry, Wendy Leadbeater, Ben A Scheven
Dental pulp stem cells (DPSC) are neural crest-derived ecto-mesenchymal stem cells that can relatively easily and non-invasively be isolated from the dental pulp of extracted postnatal and adult teeth. Accumulating evidence suggests that DPSC have great promise as a cellular therapy for central nervous system (CNS) and retinal injury and disease. The mode of action by which DPSC confer therapeutic benefit may comprise multiple pathways, in particular, paracrine-mediated processes which involve a wide array of secreted trophic factors and is increasingly regarded as the principal predominant mechanism...
June 7, 2016: Stem Cells
Hongmin Yun, Yi Zhou, Andrew Wills, Yiqin Du
Intraocular pressure (IOP) is still the main treatment target for glaucoma. Outflow resistance mainly exists at the trabecular meshwork (TM) outflow pathway, which is responsible for IOP regulation. Changes of TM cellularity and TM extracellular matrix turnover may play important roles in IOP regulation. In this article, we review basic anatomy and physiology of the outflow pathway and TM stem cell characteristics regarding the location, isolation, identification and function. TM stem cells are localized at the insert region of the TM and are label-retaining in vivo...
June 2016: Journal of Ocular Pharmacology and Therapeutics
Kohji Nishida
Japan faces an aging population and a declining birth rate, so medical professionals and the public are seeking next-generation ophthalmological treatments to preserve and restore visual function. Two fields lie at the heart of this future concept of ophthalmological treatments. The first is predictive medicine and early intervention and treatment. This field is based on precision medicine to treat chronic conditions such as keratoconus, glaucoma, and macular degeneration while the condition is latent or soon after it has developed...
March 2016: Nippon Ganka Gakkai Zasshi
Xitiz Chamling, Valentin M Sluch, Donald J Zack
PURPOSE: Currently, the only available and approved treatments for glaucoma are various pharmacologic, laser-based, and surgical procedures that lower IOP. Although these treatments can be effective, they are not always sufficient, and they cannot restore vision that has already been lost. The goal of this review is to briefly assess current developments in the application of stem cell biology to the study and treatment of glaucoma and other forms of optic neuropathy. METHODS: A combined literature review and summary of the glaucoma-related discussion at the 2015 "Sight Restoration Through Stem Cell Therapy" meeting that was sponsored by the Ocular Research Symposia Foundation (ORSF)...
April 1, 2016: Investigative Ophthalmology & Visual Science
Hong Ouyang, Jeffrey L Goldberg, Shuyi Chen, Wei Li, Guo-Tong Xu, Wei Li, Kang Zhang, Robert B Nussenblatt, Yizhi Liu, Ting Xie, Chi-Chao Chan, Donald J Zack
Stem cells hold promise for treating a wide variety of diseases, including degenerative disorders of the eye. The eye is an ideal organ for stem cell therapy because of its relative immunological privilege, surgical accessibility, and its being a self-contained system. The eye also has many potential target diseases amenable to stem cell-based treatment, such as corneal limbal stem cell deficiency, glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa (RP). Among them, AMD and glaucoma are the two most common diseases, affecting over 200 million people worldwide...
2016: International Journal of Molecular Sciences
Sarah K Ohlemacher, Akshayalakshmi Sridhar, Yucheng Xiao, Alexandra E Hochstetler, Mansoor Sarfarazi, Theodore R Cummins, Jason S Meyer
Human pluripotent stem cells (hPSCs), including both embryonic and induced pluripotent stem cells, possess the unique ability to readily differentiate into any cell type of the body, including cells of the retina. Although previous studies have demonstrated the ability to differentiate hPSCs to a retinal lineage, the ability to derive retinal ganglion cells (RGCs) from hPSCs has been complicated by the lack of specific markers with which to identify these cells from a pluripotent source. In the current study, the definitive identification of hPSC-derived RGCs was accomplished by their directed, stepwise differentiation through an enriched retinal progenitor intermediary, with resultant RGCs expressing a full complement of associated features and proper functional characteristics...
June 2016: Stem Cells
Robert Hennig, Sabrina Kuespert, Alexandra Haunberger, Achim Goepferich, Rudolf Fuchshofer
The major risk factor for primary open-angle glaucoma is increased intraocular pressure stemming from elevated outflow resistance in the trabecular meshwork (TM) region. Integrins play a pivotal role in the TM by influencing its biological properties and growth factor signaling. Pathologic changes in the TM are partially mediated by growth factors like connective tissue growth factor (CTGF). Specific targeting of TM cells could play a critical clinical role by increasing the therapeutic efficacy of nanoparticles, e...
March 14, 2016: Journal of Drug Targeting
Ben Mead, Lisa J Hill, Richard J Blanch, Kelly Ward, Ann Logan, Martin Berry, Wendy Leadbeater, Ben A Scheven
BACKGROUND AIMS: Glaucoma is a leading cause of irreversible blindness involving loss of retinal ganglion cells (RGC). Mesenchymal stromal cells (MSC) have shown promise as a paracrine-mediated therapy for compromised neurons. It is, however, unknown whether dental pulp stem cells (DPSC) are effective as a cellular therapy in glaucoma and how their hypothesized influence compares with other more widely researched MSC sources. The present study aimed to compare the efficacy of adipose-derived stem cells, bone marrow-derived MSC (BMSC) and DPSC in preventing the loss of RGC and visual function when transplanted into the vitreous of glaucomatous rodent eyes...
April 2016: Cytotherapy
Cynthia A Gossman, John Christie, Mark K Webster, David M Linn, Cindy L Linn
BACKGROUND: Glaucoma is characterized as a neuropathic disease that causes progressive degeneration of retinal ganglion cells (RGCs) in the retina, resulting in irreversible loss of vision. All conventional treatments for glaucoma are focused on reducing intraocular pressure (IOP) in the anterior chamber of the eye. However, these treatments alone are insufficient to halt the progression of the disease. As a result, neuroprotective strategies have been developed that prevent retinal neuron loss and disease progression...
2016: Current Pharmaceutical Design
Thais S Tanaka, Hakan Demirci
PURPOSE: Cryopreserved ultra-thick human amniotic membrane (AM) is used for glaucoma surgery. We evaluated the use of cryopreserved ultra-thick human AM for conjunctival surface reconstruction after excision of a conjunctival tumor. METHODS: We retrospectively reviewed the medical records of 28 patients who underwent conjunctival surface reconstruction with cryopreserved ultra-thick human AM after excision of the tumor. The AM was secured to the surrounding conjunctiva and underlying sclera with interrupted 8-0 Vicryl sutures...
April 2016: Cornea
Joseph C Giacalone, Luke A Wiley, Erin R Burnight, Allison E Songstad, Robert F Mullins, Edwin M Stone, Budd A Tucker
Whether we are driving to work or spending time with loved ones, we depend on our sense of vision to interact with the world around us. Therefore, it is understandable why blindness for many is feared above death itself. Heritable diseases of the retina, such as glaucoma, age-related macular degeneration, and retinitis pigmentosa, are major causes of blindness worldwide. The recent success of gene augmentation trials for the treatment of RPE65-associated Leber congenital amaurosis has underscored the need for model systems that accurately recapitulate disease...
February 2016: Stem Cells Translational Medicine
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