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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Human Fetal Pigmented Ciliary Epithelium Stem Cells have Regenerative Capacity in the Murine Retinal Degeneration Model of Laser Injury

Author(s): Sridhar Bammidi, Shweta Modgil, Jaswinder Kalra and Akshay Anand*

Volume 16, Issue 3, 2019

Page: [187 - 193] Pages: 7

DOI: 10.2174/1567202616666190618123931

Price: $65

Abstract

Background: Retinal degeneration and related eye disorders have limited treatment interventions. Since stem cell therapy has shown promising results, ciliary epithelium (CE) derived stem cells could be a better choice given the fact that cells from eye niche can better integrate with the degenerating retina, rewiring the synaptic damage.

Objective: To test the effect of human fetal pigmented ciliary epithelium-derived neurospheres in the mouse model of laser-induced retinal degeneration.

Methods: C57 male mice were subjected to retinal injury by Laser photocoagulation. Human fetal pigmented ciliary epithelium was obtained from post-aborted human eyeballs and cultured with epidermal growth factor (rhEGF) and fibroblast growth factor (rhFGF). The six day neurospheres were isolated, dissociated and transplanted into the subretinal space of the laser injured mice at the closest proximity to Laser shots. Mice were analyzed for functional vision through electroretinogram (ERG) and sacrificed at 1 week and 12 week time points. Retinal, Neurotropic, Apoptotic and proliferation markers were analysed using real-time polymerase chain reaction (PCR).

Results: The CE neurospheres showed an increase in the expression of candidate genes analyzed in the study at 1 week time point, which sustained for longer time point of 12 weeks.

Conclusion: We showed the efficacy of human CE cells in the regeneration of retinal degeneration in murine model for the first time. CE cells need to be explored comprehensively both in disease and degeneration.

Keywords: Ciliary epithelium, laser injury, retinal degeneration, subretinal, transplantation, Age-related Macular Degeneration (AMD).

« Previous Next »
[1]
Mitchell P, Liew G, Gopinath B, Wong TY. Age-related macular degeneration. Lancet 2018; 392(10153): 1147-59.
[2]
Hinkle JW, Relhan N, Flynn HW Jr. Lipemia retinalis, macular edema, and vision loss in a diabetic patient with a history of type IV hypertriglyceridemia and pancreatitis. Case Rep Ophthalmol 2018; 9(3): 425-30.
[3]
Mtanes K, Mimouni M, Zayit-Soudry S. Laser pointer-induced maculopathy: More than meets the eye. J Pediatr Ophthalmol Strabismus 2018; 55(5): 312-8.
[4]
Zakrzewski H, Chung H, Sanders E, Hanson C, Ford B. Evaluation of occupational ocular trauma: Are we doing enough to promote eye safety in the workplace? Can J Ophthalmol 2017; 52(4): 338-42.
[5]
Miao H, Hou J. Influent factors for treating procedure of cytomegalovirus retinitis after allogeneic bone marrow hematopoietic stem cell transplantation. Zhonghua Yan Ke Za Zhi 2017; 53(10): 740-5.
[6]
Fiori A, Terlizzi V, Kremer H, et al. Mesenchymal stromal/stem cells as potential therapy in diabetic retinopathy. Immunobiology 2018; 223(12): 729-43.
[7]
Lakowski J, Gonzalez-Cordero A, West EL, et al. Transplantation of photoreceptor precursors isolated via a cell surface biomarker panel from embryonic stem cell-derived self-forming retina. Stem Cells 2015; 33(8): 2469-82.
[8]
Cristante E, Liyanage SE, Sampson RD, et al. Late neuroprogenitors contribute to normal retinal vascular development in a Hif2a-dependent manner. Development 2018; 145(8): 145.
[9]
Liu Y, Chen SJ, Li SY, et al. Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients. Stem Cell Res Ther 2017; 8(1): 209.
[10]
Fischer AJ, Bosse JL, El-Hodiri HM. The ciliary marginal zone (CMZ) in development and regeneration of the vertebrate eye. Exp Eye Res 2013; 116: 199-204.
[11]
Wan Y, Almeida AD, Rulands S, et al. The ciliary marginal zone of the zebrafish retina: Clonal and time-lapse analysis of a continuously growing tissue. Development 2016; 143(7): 1099-107.
[12]
Fischer AJ, Bosse JL, El-Hodiri HM. Reprint of: The ciliary marginal zone (CMZ) in development and regeneration of the vertebrate eye. Exp Eye Res 2014; 123: 115-20.
[13]
Moshiri A, McGuire CR, Reh TA. Sonic hedgehog regulates proliferation of the retinal ciliary marginal zone in posthatch chicks. Dev Dyn 2005; 233(1): 66-75.
[14]
Yoshii C, Ueda Y, Okamoto M, Araki M. Neural retinal regeneration in the anuran amphibian Xenopus laevis post-metamorphosis: Transdifferentiation of retinal pigmented epithelium regenerates the neural retina. Dev Biol 2007; 303(1): 45-56.
[15]
Das AV, James J, Rahnenführer J, et al. Retinal properties and potential of the adult mammalian ciliary epithelium stem cells. Vision Res 2005; 45(13): 1653-66.
[16]
Abburi C, Prabhakar S, Kalra J, Huria A, Anand A. Vascular endothelial growth factor (VEGF) induced proliferation of human fetal derived ciliary epithelium stem cells is mediated by jagged-N cadherin pathway. Curr Neurovasc Res 2013; 10(2): 93-102.
[17]
Wetts R, Serbedzija GN, Fraser SE. Cell lineage analysis reveals multipotent precursors in the ciliary margin of the frog retina. Dev Biol 1989; 136(1): 254-63.
[18]
Cicero SA, Johnson D, Reyntjens S, et al. Cells previously identified as retinal stem cells are pigmented ciliary epithelial cells. Proc Natl Acad Sci USA 2009; 106(16): 6685-90.
[19]
Tropepe V, Coles BL, Chiasson BJ, et al. Retinal stem cells in the adult mammalian eye. Science 2000; 287(5460): 2032-6.
[20]
Ahmad I, Tang L, Pham H. Identification of neural progenitors in the adult mammalian eye. Biochem Biophys Res Commun 2000; 270(2): 517-21.
[21]
Guduric-Fuchs J, Chen W, Price H, Archer DB, Cogliati T. RPE and neuronal differentiation of allotransplantated porcine ciliary epithelium-derived cells. Mol Vis 2011; 17: 2580-95.
[22]
Kuwahara A, Ozone C, Nakano T, Saito K, Eiraku M, Sasai Y. Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue. Nat Commun 2015; 6: 6286.
[23]
Miyake A, Araki M. Retinal stem/progenitor cells in the ciliary marginal zone complete retinal regeneration: A study of retinal regeneration in a novel animal model. Dev Neurobiol 2014; 74(7): 739-56.
[24]
Song H, Wang D, De Jesus Perez F, et al. Rhythmic expressed clock regulates the transcription of proliferating cellular nuclear antigen in teleost retina. Exp Eye Res 2017; 160: 21-30.
[25]
Denayer T, Locker M, Borday C, et al. Canonical Wnt signaling controls proliferation of retinal stem/progenitor cells in postembryonic Xenopus eyes. Stem Cells 2008; 26(8): 2063-74.
[26]
Abdouh M, Bernier G. In vivo reactivation of a quiescent cell population located in the ocular ciliary body of adult mammals. Exp Eye Res 2006; 83(1): 153-64.
[27]
Horsford DJ, Nguyen MT, Sellar GC, Kothary R, Arnheiter H, McInnes RR. Chx10 repression of Mitf is required for the maintenance of mammalian neuroretinal identity. Development 2005; 132(1): 177-87.
[28]
Caicedo A, Espinosa-Heidmann DG, Piña Y, Hernandez EP, Cousins SW. Blood-derived macrophages infiltrate the retina and activate Muller glial cells under experimental choroidal neovascularization. Exp Eye Res 2005; 81(1): 38-47.
[29]
Cruz-Guilloty F, Saeed AM, Echegaray JJ, et al. Infiltration of proinflammatory m1 macrophages into the outer retina precedes damage in a mouse model of age-related macular degeneration. Int J Inflamm 2013; 2013: 503725.
[30]
Xu H, Iglesia DD, Kielczewski JL, et al. Characteristics of progenitor cells derived from adult ciliary body in mouse, rat, and human eyes. Invest Ophthalmol Vis Sci 2007; 48(4): 1674-82.

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