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Retina, transplantation

Tiago Santos-Ferreira, Sílvia Llonch, Oliver Borsch, Kai Postel, Jochen Haas, Marius Ader
Pre-clinical studies provided evidence for successful photoreceptor cell replacement therapy. Migration and integration of donor photoreceptors into the retina has been proposed as the underlying mechanism for restored visual function. Here we reveal that donor photoreceptors do not structurally integrate into the retinal tissue but instead reside between the photoreceptor layer and the retinal pigment epithelium, the so-called sub-retinal space, and exchange intracellular material with host photoreceptors...
October 4, 2016: Nature Communications
R A Pearson, A Gonzalez-Cordero, E L West, J R Ribeiro, N Aghaizu, D Goh, R D Sampson, A Georgiadis, P V Waldron, Y Duran, A Naeem, M Kloc, E Cristante, K Kruczek, K Warre-Cornish, J C Sowden, A J Smith, R R Ali
Photoreceptor replacement by transplantation is proposed as a treatment for blindness. Transplantation of healthy photoreceptor precursor cells into diseased murine eyes leads to the presence of functional photoreceptors within host retinae that express an array of donor-specific proteins. The resulting improvement in visual function was understood to be due to donor cells integrating within host retinae. Here, however, we show that while integration occurs the majority of donor-reporter-labelled cells in the host arises as a result of material transfer between donor and host photoreceptors...
October 4, 2016: Nature Communications
Min Yu, Sanja Bojic, Gustavo S Figueiredo, Paul Rooney, Julian de Havilland, Anne Dickinson, Francisco C Figueiredo, Majlinda Lako
The cornea is a self-renewing tissue located at the front of the eye. Its transparency is essential for allowing light to focus onto the retina for visual perception. The continuous renewal of corneal epithelium is supported by limbal stem cells (LSCs) which are located in the border region between conjunctiva and cornea known as the limbus. Ex vivo expansion of LSCs has been successfully applied in the last two decades to treat patients with limbal stem cell deficiency (LSCD). Various methods have been used for their expansion, yet the most widely used culture media contains a number of ingredients derived from animal sources which may compromise the safety profile of human LSC transplantation...
September 28, 2016: Experimental Eye Research
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
Junhua Wang, Peter D Westenskow, Mingliang Fang, Martin Friedlander, Gary Siuzdak
Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic 'fingerprint' of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques...
October 28, 2016: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
Sunao Sugita, Yuko Iwasaki, Kenichi Makabe, Hiroyuki Kamao, Michiko Mandai, Takashi Shiina, Kazumasa Ogasawara, Yasuhiko Hirami, Yasuo Kurimoto, Masayo Takahashi
There is an ongoing controversy as to whether major histocompatibility complex (MHC) matching is a solution for allogeneic stem cell transplantation. In the present study, we established retinal pigment epithelial (RPE) cells from induced pluripotent stem cells (iPSCs) in MHC homozygote donors. We observed no rejection signs in iPSC-derived RPE allografts of MHC-matched animal models without immunosuppression, whereas there were immune attacks around the graft and retinal tissue damage in MHC-mismatched models...
October 11, 2016: Stem Cell Reports
Cassie A Ludwig, Theodore Leng
The authors report two cases of posterior retinotomy closure following subretinal stem cell transplantation for age-related macular degeneration with a 30-gauge needle - a larger bore needle than those used in prior studies. Partial retinotomy closure was seen on optical coherence tomography within 24 hours in one patient, whereas complete closure occurred by the 5-month and 1-year follow-up visits. A trace retinal hemorrhage occurred in one case, with resolution by 12 weeks. These findings demonstrate the likelihood of uncomplicated, spontaneous retinotomy closure following subretinal stem cell transplantation with a 30-gauge needle...
September 1, 2016: Ophthalmic Surgery, Lasers & Imaging Retina
Benjamin Bakondi, Sergey Girman, Bin Lu, Shaomei Wang
: : We previously demonstrated that subretinal injection (SRI) of isogenic mesenchymal stem cells (MSCs) reduced the severity of retinal degeneration in Royal College of Surgeons rats in a focal manner. In contrast, intravenous MSC infusion (MSC(IV)) produced panoptic retinal rescue. By combining these treatments, we now show that MSC(IV) supplementation potentiates the MSC(SRI)-mediated rescue of photoreceptors and visual function. Electrophysiological recording from superior colliculi revealed 3...
September 9, 2016: Stem Cells Translational Medicine
Ping Song, Lynn Dudinsky, Joseph Fogerty, Robert Gaivin, Brian D Perkins
PURPOSE: Mutations in the gene ARL13B cause the classical form of Joubert syndrome, an autosomal recessive ciliopathy with variable degrees of retinal degeneration. As second-site modifier alleles can contribute to retinal pathology in ciliopathies, animal models provide a unique platform to test how genetic interactions modulate specific phenotypes. In this study, we analyzed the zebrafish arl13b mutant for retinal degeneration and for epistatic relationships with the planar cell polarity protein (PCP) component vangl2...
August 1, 2016: Investigative Ophthalmology & Visual Science
Chi-Hsien Peng, Jen-Hua Chuang, Mong-Lien Wang, Yong-Yu Jhan, Ke-Hung Chien, Yu-Chien Chung, Kuo-Hsuan Hung, Chia-Ching Chang, Chao-Kuei Lee, Wei-Lien Tseng, De-Kuang Hwang, Chia-Hsien Hsu, Tai-Chi Lin, Shih-Hwa Chiou, Shih-Jen Chen
Advanced age-related macular degeneration (AMD) may lead to geographic atrophy or fibrovascular scar at macular, dysfunctional retinal microenvironment, and cause profound visual loss. Recent clinical trials have implied the potential application of pluripotent cell-differentiated retinal pigment epithelial cells (dRPEs) and membranous scaffolds implantation in repairing the degenerated retina in AMD. However, the efficacy of implanted membrane in immobilization and supporting the viability and functions of dRPEs, as well as maintaining the retinal microenvironment is still unclear...
August 22, 2016: Oncotarget
Ma'ayan Semo, Nasrin Haamedi, Lara Stevanato, David Carter, Gary Brooke, Michael Young, Peter Coffey, John Sinden, Sara Patel, Anthony Vugler
PURPOSE: We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. METHODS: Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting...
July 2016: Translational Vision Science & Technology
Jordi Monés, Marta Leiva, Teresa Peña, Gema Martínez, Marc Biarnés, Miriam Garcia, Anna Serrano, Eduardo Fernandez
PURPOSE: To establish the dose of subretinal sodium iodate (NaIO3) in order to create a toxin-induced large animal model of selective circumscribed atrophy of outer retinal layers, the retinal pigment epithelium (RPE), and photoreceptors, by spectral-domain optical coherence tomography (SD-OCT) and immunocytochemistry. METHODS: Fifteen male and female healthy Yorkshire pigs received unilateral subretinal escalating doses of NaIO3 under general anesthesia. In all the animals, volumes of 0...
August 1, 2016: Investigative Ophthalmology & Visual Science
I P Seitz, K Achberger, S Liebau, M D Fischer
In ophthalmology, regenerative medicine is rapidly becoming a reality. Cell based treatment strategies in end stage retinal degeneration may be of therapeutic value, whatever the mechanism of disease mechanism. However, while corneal transplantation is commonly performed with excellent results, many obstacles must be overcome before retinal transplants can become clinically useful. The major problems are the production of appropriate transplants and functional integration in situ. New technologies allow the production of autologous transplants by inducing pluripotency in adult somatic cells...
August 1, 2016: Klinische Monatsblätter Für Augenheilkunde
Hideto Koso, Asano Tsuhako, Chen-Yi Lai, Yukihiro Baba, Makoto Otsu, Kazuko Ueno, Masao Nagasaki, Yutaka Suzuki, Sumiko Watanabe
Neurodegeneration has been shown to induce microglial activation and the infiltration of monocyte-derived macrophages into the CNS, resulting in the coexistence of these two populations within the same lesion, though their distinct features remain elusive. To investigate the impact of rod photoreceptor degeneration on microglial activation, we generated a toxin-mediated genetic model of rod degeneration. Rod injury induced microglial proliferation and migration toward the photoreceptors. Bone marrow transplantation revealed the invasion of monocyte-derived macrophages into the retina, with microglia and the infiltrating macrophages showing distinct distribution patterns in the retina...
November 2016: Glia
Bikun Xian, Yichi Zhang, Yuting Peng, Jianfa Huang, Weihua Li, Wencong Wang, Min Zhang, Kaijing Li, Hening Zhang, Minglei Zhao, Xing Liu, Bing Huang
: : Adult human peripheral blood mononuclear cells (hPBMCs) exhibit pluripotency in vitro and so may be a valuable cell source for regenerative therapies. The efficacy of such therapies depends on the survival, differentiation, migration, and integration capacity of hPBMCs in specific tissues. In this study, we examined these capacities of transplanted hPBMCs in mouse retina as well functional improvement after transplant. We isolated hPBMCs and preinduced them for 4 days in media preconditioned with postnatal day 1 rat retina explants...
July 25, 2016: Stem Cells Translational Medicine
Daniela Sanges, Giacoma Simonte, Umberto Di Vicino, Neus Romo, Isabel Pinilla, Marta Nicolás, Maria Pia Cosma
Vision impairments and blindness caused by retinitis pigmentosa result from severe neurodegeneration that leads to a loss of photoreceptors, the specialized light-sensitive neurons that enable vision. Although the mammalian nervous system is unable to replace neurons lost due to degeneration, therapeutic approaches to reprogram resident glial cells to replace retinal neurons have been proposed. Here, we demonstrate that retinal Müller glia can be reprogrammed in vivo into retinal precursors that then differentiate into photoreceptors...
August 1, 2016: Journal of Clinical Investigation
Juan Yang, Maosong Xie, Weidong Zheng, Jianzhang Hu, Qiang Qu
Objective To investigate the potential of the treatment of growth-associated protein 43 (GAP43) gene-modified bone marrow-derived mesenchymal stem cells (BMSCs) for retinitis pigmentosa (RP). Methods BMSCs were isolated and cultured by adherence method. By transfecting GAP43 gene into BMSCs via a lentivirus vector, we got GAP43 gene-modified BMSCs. Sixty-three Royal College of Surgeons (RCS) rats were randomly divided into three groups: experimental group, negative control group and blank control group. The experimental rats received subretinal injection of GAP43 gene-modified BMSCs...
August 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Alona O Barnea-Cramer, Wei Wang, Shi-Jiang Lu, Mandeep S Singh, Chenmei Luo, Hongguang Huo, Michelle E McClements, Alun R Barnard, Robert E MacLaren, Robert Lanza
Photoreceptor degeneration due to retinitis pigmentosa (RP) is a primary cause of inherited retinal blindness. Photoreceptor cell-replacement may hold the potential for repair in a completely degenerate retina by reinstating light sensitive cells to form connections that relay information to downstream retinal layers. This study assessed the therapeutic potential of photoreceptor progenitors derived from human embryonic and induced pluripotent stem cells (ESCs and iPSCs) using a protocol that is suitable for future clinical trials...
2016: Scientific Reports
Kiyoharu J Miyagishima, Qin Wan, Barbara Corneo, Ruchi Sharma, Mostafa R Lotfi, Nathan C Boles, Fang Hua, Arvydas Maminishkis, Congxiao Zhang, Timothy Blenkinsop, Vladimir Khristov, Balendu S Jha, Omar S Memon, Sunita D'Souza, Sally Temple, Sheldon S Miller, Kapil Bharti
: : Induced pluripotent stem cells (iPSCs) can be efficiently differentiated into retinal pigment epithelium (RPE), offering the possibility of autologous cell replacement therapy for retinal degeneration stemming from RPE loss. The generation and maintenance of epithelial apical-basolateral polarity is fundamental for iPSC-derived RPE (iPSC-RPE) to recapitulate native RPE structure and function. Presently, no criteria have been established to determine clonal or donor based heterogeneity in the polarization and maturation state of iPSC-RPE...
July 11, 2016: Stem Cells Translational Medicine
Tiago Santos-Ferreira, Manuela Völkner, Oliver Borsch, Jochen Haas, Peter Cimalla, Praveen Vasudevan, Peter Carmeliet, Denis Corbeil, Stylianos Michalakis, Edmund Koch, Mike O Karl, Marius Ader
PURPOSE: Preclinical studies on photoreceptor transplantation provided evidence for restoration of visual function with pluripotent stem cells considered as a potential source for sufficient amounts of donor material. Adequate preclinical models representing retinal disease conditions of potential future patients are needed for translation research. Here we compared transplant integration in mouse models with mild (prominin1-deficient; Prom1-/-) or severe (cone photoreceptor function loss 1/rhodopsin-deficient double-mutant; Cpfl1/Rho-/-) cone-rod degeneration...
June 1, 2016: Investigative Ophthalmology & Visual Science
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