Choroideremia

2021 ◽  
pp. 213-217
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Visual Acuity ◽  
Retinal Pigment Epithelium ◽  
Small Molecules ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Prosthesis ◽  
Progressive Reduction ◽  
Progressive Degeneration

Choroideremia is X-linked chorioretinal dystrophy characterized by progressive degeneration of the choroid, retinal pigment epithelium (RPE), and retina. The disease is caused by mutations in the CHM gene which is known to be related to membrane transportation protein in the retina and RPE. Male-affected cases have nyctalopia and progressive reduction in visual acuity. Female-affected cases are carriers. This disease is considered incurable, although new promising treatments have been recently introduced such as gene therapy, stem cells, small molecules, and retinal prosthesis.

scholarly journals Efficient differentiation of human embryonic stem cells to retinal pigment epithelium under defined conditions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ioannis J. Limnios ◽  
Yu-Qian Chau ◽  
Stuart J. Skabo ◽  
Denver C. Surrao ◽  
Helen C. O’Neill
Keyword(s):  
Stem Cells ◽  
Retinal Pigment Epithelium ◽  
Small Molecules ◽  
Human Embryonic Stem Cells ◽  
Cell Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Efficient Production ◽  
Rpe Cells

Abstract Age-related macular degeneration (AMD) is a highly prevalent form of blindness caused by loss death of cells of the retinal pigment epithelium (RPE). Transplantation of pluripotent stem cell (PSC)-derived RPE cells is considered a promising therapy to regenerate cell function and vision. Objective The objective of this study is to develop a rapid directed differentiation method for production of RPE cells from PSC which is rapid, efficient, and fully defined and produces cells suitable for clinical use. Design A protocol for cell growth and differentiation from hESCs was developed to induce differentiation through screening small molecules which regulated a primary stage of differentiation to the eyefield progenitor, and then, a subsequent set of molecules to drive differentiation to RPE cells. Methods for cell plating and maintenance have been optimized to give a homogeneous population of cells in a short 14-day period, followed by a procedure to support maturation of cell function. Results We show here the efficient production of RPE cells from human embryonic stem cells (hESCs) using small molecules in a feeder-free system using xeno-free/defined medium. Flow cytometry at day 14 showed ~ 90% of cells expressed the RPE markers MITF and PMEL17. Temporal gene analysis confirmed differentiation through defined cell intermediates. Mature hESC-RPE cell monolayers exhibited key morphological, molecular, and functional characteristics of the endogenous RPE. Conclusion This study identifies a novel cell differentiation process for rapid and efficient production of retinal RPE cells directly from hESCs. The described protocol has utility for clinical-grade cell production for human therapy to treat AMD.

scholarly journals Combined Hamartoma of the Retina and Retinal Pigment Epithelium in a Patient with Gorlin Syndrome: Spontaneous Partial Resolution of Traction Caused by Epiretinal Membrane

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
José L. Sánchez-Vicente ◽  
Miguel Contreras-Díaz ◽  
Trinidad Rueda ◽  
Enrique Rodríguez de la Rúa-Franch ◽  
Fredy E. Molina-Socola ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinal Pigment Epithelium ◽  
Epiretinal Membrane ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Spontaneous Resolution ◽  
Fundus Examination ◽  
Gorlin Syndrome ◽  
Clinical Context

Purpose. To describe the case of spontaneous resolution of epiretinal membrane in a patient with Combined Hamartoma of the Retina and Retinal Pigment Epithelium (CHR-RPE), in the clinical context of Gorlin Syndrome (GS).Methods. Observational case report of a 12-year-old female patient is presented. The diagnosis of CHRRPE was made by OCT and fundus examination, which showed a mound of disorganized tissue originating from retina and retinal pigment epithelium. Epiretinal membrane (EM) was also detected. Genetic study was performed to confirm the diagnosis of GS.Results. The patient was observed for 39 months, showing spontaneous resolution of the traction caused by the EM and improvement in visual acuity (VA), which was 20/80 at initial presentation, rising to 20/40 after follow-up period.Conclusions. The presence of EM in CHR-REP is a cause of reduction of visual acuity. Management of this condition is controversial; however, we would like to highlight that spontaneous resolution of the traction caused by EM is possible, resulting in recovery of VA.

scholarly journals Engineering Efficient Retinal Pigment Epithelium Differentiation From Human Pluripotent Stem Cells

2014 ◽  
Vol 3 (11) ◽  
pp. 1295-1304 ◽  
Author(s):  
Amelia Lane ◽  
Lissa Rachel Philip ◽  
Ludmila Ruban ◽  
Kate Fynes ◽  
Matthew Smart ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinal Pigment Epithelium ◽  
Pluripotent Stem Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Human Pluripotent Stem Cells

scholarly journals Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease

2017 ◽  
Vol 114 (15) ◽  
pp. 3987-3992 ◽  
Author(s):  
Tamara L. Lenis ◽  
Shanta Sarfare ◽  
Zhichun Jiang ◽  
Marcia B. Lloyd ◽  
Dean Bok ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Retinal Pigment Epithelium ◽  
Complement System ◽  
Complement Activation ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Host Cells ◽  
Etiologic Factor ◽  
Photoreceptor Degeneration ◽  
The Complement System

Recessive Stargardt macular degeneration (STGD1) is caused by mutations in the gene for the ABCA4 transporter in photoreceptor outer segments. STGD1 patients and Abca4−/− (STGD1) mice exhibit buildup of bisretinoid-containing lipofuscin pigments in the retinal pigment epithelium (RPE), increased oxidative stress, augmented complement activation and slow degeneration of photoreceptors. A reduction in complement negative regulatory proteins (CRPs), possibly owing to bisretinoid accumulation, may be responsible for the increased complement activation seen on the RPE of STGD1 mice. CRPs prevent attack on host cells by the complement system, and complement receptor 1-like protein y (CRRY) is an important CRP in mice. Here we attempted to rescue the phenotype in STGD1 mice by increasing expression of CRRY in the RPE using a gene therapy approach. We injected recombinant adeno-associated virus containing the CRRY coding sequence (AAV-CRRY) into the subretinal space of 4-wk-old Abca4−/− mice. This resulted in sustained, several-fold increased expression of CRRY in the RPE, which significantly reduced the complement factors C3/C3b in the RPE. Unexpectedly, AAV-CRRY–treated STGD1 mice also showed reduced accumulation of bisretinoids compared with sham-injected STGD1 control mice. Furthermore, we observed slower photoreceptor degeneration and increased visual chromophore in 1-y-old AAV-CRRY–treated STGD1 mice. Rescue of the STGD1 phenotype by AAV-CRRY gene therapy suggests that complement attack on the RPE is an important etiologic factor in STGD1. Modulation of the complement system by locally increasing CRP expression using targeted gene therapy represents a potential treatment strategy for STGD1 and other retinopathies associated with complement dysregulation.

scholarly journals Intercellular Trafficking of Adenovirus-Delivered HSV VP22 from the Retinal Pigment Epithelium to the Photoreceptors—Implications for Gene Therapy

2002 ◽  
Vol 6 (6) ◽  
pp. 813-823 ◽  
Author(s):  
Siobhan M. Cashman ◽  
Sonia L. Sadowski ◽  
David J. Morris ◽  
Jeanne Frederick ◽  
Rajendra Kumar-Singh
Keyword(s):  
Gene Therapy ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Intercellular Trafficking
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