scholarly journals Gene replacement therapy restores RCBTB1 expression and cilium length in patient‐derived retinal pigment epithelium

2021 ◽  
Author(s):  
Zhiqin Huang ◽  
Dan Zhang ◽  
Shang‐Chih Chen ◽  
Luke Jennings ◽  
Livia S. Carvalho ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Replacement Therapy ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Gene Replacement ◽  
Gene Replacement Therapy ◽  
Cilium Length

scholarly journals Evaluation for Retinal Therapy for RPE65 Variation Assessed in hiPSC Retinal Pigment Epithelial Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Benjamin M. Nash ◽  
To Ha Loi ◽  
Milan Fernando ◽  
Amin Sabri ◽  
James Robinson ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Early Onset ◽  
Retinal Pigment ◽  
Gene Replacement ◽  
Compound Heterozygous ◽  
Retinal Cells ◽  
Exon 2 ◽  
Rpe Cells ◽  
Gene Replacement Therapy ◽  
Synonymous Variant

Human induced pluripotent stem cells (hiPSCs) generated from patients and the derivative retinal cells enable the investigation of pathological and novel variants in relevant cell populations. Biallelic pathogenic variants in RPE65 cause early-onset severe retinal dystrophy (EOSRD) or Leber congenital amaurosis (LCA). Increasingly, regulatory-approved in vivo RPE65 retinal gene replacement therapy is available for patients with these clinical features, but only if they have biallelic pathological variants and sufficient viable retinal cells. In our cohort of patients, we identified siblings with early-onset severe retinal degeneration where genomic studies revealed compound heterozygous variants in RPE65, one a known pathogenic missense variant and the other a novel synonymous variant of uncertain significance. The synonymous variant was suspected to affect RNA splicing. Since RPE65 is very poorly expressed in all tissues except the retinal pigment epithelium (RPE), we generated hiPSC-derived RPE cells from the parental carrier of the synonymous variant. Sequencing of RNA obtained from hiPSC-RPE cells demonstrated heterozygous skipping of RPE65 exon 2 and the introduction of a premature stop codon in the mRNA. Minigene studies confirmed the splicing aberration. Results from this study led to reclassification of the synonymous variant to a pathogenic variant, providing the affected patients with access to RPE65 gene replacement therapy.

Sources of retinal pigment epithelium (RPE) for replacement therapy

2010 ◽  
Vol 95 (4) ◽  
pp. 445-449 ◽  
Author(s):  
E. Lee ◽  
R. E. MacLaren
Keyword(s):  
Retinal Pigment Epithelium ◽  
Replacement Therapy ◽  
Pigment Epithelium ◽  
Retinal Pigment

scholarly journals Novel non-sense mutation in RP2 (c.843_844insT/p.Arg282fs) is associated with a severe phenotype of retinitis pigmentosa without evidence of primary retinal pigment epithelium involvement

2019 ◽  
Vol 12 (5) ◽  
pp. e224451 ◽  
Author(s):  
Faye Horner ◽  
James Wawrzynski ◽  
Robert MacLaren
Keyword(s):  
Retinal Pigment Epithelium ◽  
Retinitis Pigmentosa ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Gene Replacement ◽  
Viral Gene ◽  
Retinal Layer ◽  
Viral Gene Therapy ◽  
Gene Therapy Vectors ◽  
Route Of Delivery

Retinitis pigmentosa (RP) relates to a heterogeneous group of rod-cone dystrophies of varying genetic aetiology. There is currently great interest in gene replacement therapy. Phenotyping is of particular importance because some RP genes are expressed ubiquitously and it is critically important to understand which retinal layer is primarily affected. RP2 is increasingly diagnosed in patients suffering from X-linked RP, which causes outer retinal degeneration. We present a case of a previously unreported null mutation in RP2 associated with severe RP. Loss of the retinal pigment epithelium (RPE) was noted in the central macula but not around the disc or peripherally. There was therefore no evidence of independent degeneration of the RPE. Hence despite expression in all retinal cells, RP2 deficiency does not appear to be pathogenic to the RPE. This observation may be helpful in considering the promoter and route of delivery of adeno-associated viral gene therapy vectors encoding RP2.

High-voltage electron microscopy of subretinal scar formation

1992 ◽  
Vol 50 (1) ◽  
pp. 486-487
Author(s):  
G.E. Korte ◽  
M. Marko ◽  
G. Hageman
Keyword(s):  
Electron Microscopy ◽  
Monoclonal Antibody ◽  
Retinal Pigment Epithelium ◽  
Glial Cells ◽  
High Voltage ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Sodium Iodate ◽  
High Voltage Electron Microscopy ◽  
Voltage Electron

Sodium iodate iv. damages the retinal pigment epithelium (RPE) in rabbits. Where RPE does not regenerate (e.g., 1,2) Muller glial cells (MC) forma subretinal scar that replaces RPE. The MC response was studied by HVEM in 3D computer reconstructions of serial thick sections, made using the STEREC0N program (3), and the HVEM at the NYS Dept. of Health in Albany, NY. Tissue was processed for HVEM or immunofluorescence localization of a monoclonal antibody recognizing MG microvilli (4).

Risk assessment, early diagnosis and gene replacement therapy: p53 to attack current problems in the management of ovarian cancer

1998 ◽  
Vol 5 (1) ◽  
pp. 47A-47A
Author(s):  
I RUNNEBAUM ◽  
S WANGGOHRKE ◽  
E STICKEIER ◽  
V MOEBUS ◽  
H GRILL ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Assessment ◽  
Early Diagnosis ◽  
Replacement Therapy ◽  
Gene Replacement ◽  
Gene Replacement Therapy

Study Design of STR1VE-EU, a Phase 3 Trial of AVXS-101 Gene-Replacement Therapy (GRT) in Patients With Spinal Muscular Atrophy Type 1 (SMA1) in Europe

2019 ◽  
Author(s):  
Francesco Muntoni ◽  
Giovanni Baranello ◽  
Claudio Bruno ◽  
Stefania Corti ◽  
Riccardo Masson ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Replacement Therapy ◽  
Study Design ◽  
Muscular Atrophy ◽  
Gene Replacement ◽  
Phase 3 ◽  
Spinal Muscular Atrophy Type ◽  
Gene Replacement Therapy

Comparisons of the Structural and Chemical Properties of Melanosomes Isolated from Retinal Pigment Epithelium, Iris and Choroid of Newborn and Mature Bovine Eyes¶

2005 ◽  
Vol 81 (3) ◽  
pp. 510 ◽  
Author(s):  
Yan Liu ◽  
Lian Hong ◽  
Kazumasa Wakamatsu ◽  
Shosuke Ito ◽  
Bhavin B. Adhyaru ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Chemical Properties ◽  
And Chemical Properties
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