A5060920555- Retinal Development and Disorders
- Phagocytosis and Immune Regulation
- Retinal Diseases and Treatments
- Cell Adhesion Molecules Research
- CRISPR and Genetic Engineering
- Retinal and Optic Conditions
- Circadian rhythm and melatonin
- Connexins and lens biology
- RNA regulation and disease
- Complement system in diseases
- Cellular transport and secretion
- Biomedical Research and Pathophysiology
- Pluripotent Stem Cells Research
- Retinal Imaging and Analysis
- Ocular Disorders and Treatments
- Virus-based gene therapy research
- Photoreceptor and optogenetics research
- Retinal and Macular Surgery
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Erythrocyte Function and Pathophysiology
- Redox biology and oxidative stress
- interferon and immune responses
- Genetic and Kidney Cyst Diseases
- Yersinia bacterium, plague, ectoparasites research
- SARS-CoV-2 and COVID-19 Research
Inserm
2015-2025
Institut de la Vision
2016-2025
Sorbonne Université
2015-2025
Centre National de la Recherche Scientifique
2015-2025
Wake Forest University
2020
Forest Institute
2020
Charlottesville Medical Research
2020
John Wiley & Sons (United States)
2020
Karolinska Institutet
2020
Université Paris Cité
2000-2014
Significance Human induced pluripotent stem cells (hiPSCs) could be used as an unlimited source of retinal for the treatment degenerative diseases. The production from hiPSCs personalized therapeutic approaches must comply with certain criteria, such safety, efficiency, reproducibility, and low cost. Here, we report a simple scalable differentiation process generation pigmented epithelial neural tissues containing progenitor cells. These progenitors can differentiated into all cell types,...
Atrophic age‐related macular degeneration (AMD) is associated with the subretinal accumulation of mononuclear phagocytes (MPs). Their role in promoting or inhibiting retinal unknown. We here show that atrophic AMD increased intraocular CCL2 levels and CCR2 + inflammatory monocyte infiltration patients. Using age‐ light‐induced inflammation photoreceptor Cx3cr1 knockout mice, we deficient MPs overexpress both genetic deletion pharmacological inhibition prevent recruitment, MP vivo . Our study...
Abstract Human induced pluripotent stem cells (hiPSCs) are potentially useful in regenerative therapies for retinal disease. For medical applications, therapeutic cells, such as pigmented epithelial (RPE) or photoreceptor precursors, must be generated under completely defined conditions. To this purpose, we have developed a two-step xeno-free/feeder-free (XF/FF) culture system to efficiently differentiate hiPSCs into cells. This simple method, relies only on adherent cultured chemically...
Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment fragments is critical for vision. In retina, early morning circadian rod shedding precedes synchronized uptake shed particles RPE cells. vitro, cells use integrin receptor αvβ5 particle binding. Here, we tested and function in β5 integrin–deficient mice, which specifically lack receptors. Retinal photoresponses severely declined with age β5−/− whose accumulated autofluorescent storage bodies that...
The integrin receptor alphavbeta5 controls two independent forms of interactions the retinal pigment epithelium (RPE) with adjacent photoreceptor outer segments that are essential for vision. Alphavbeta5 localizes specifically to apical microvilli RPE and contributes adhesion maintains contacts intact at all times. Additionally, synchronizes diurnal bursts phagocytosis clear segment fragments (POS) shed in a circadian rhythm. Dependence on receptors suggests extracellular matrix ensheathing...
Autosomal-recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known expressed human eye. The purpose of this study to establish prevalence and nature EYS clinically well-characterized cohort 239 sporadic arRP French cases. Direct sequencing performed 186 subjects for whom had previously been excluded by applying microarray technology. We mostly identified total 29 patients: Fifteen were predicted create...
Mutations in the ubiquitously expressed pre-mRNA processing factors 3, 8, and 31 (PRPF3, PRPF8, PRPF31) cause nonsyndromic dominant retinitis pigmentosa humans, an inherited retinal degeneration. It is unclear what mechanisms, or which cell types of retina, are affected. Transgenic mice with human mutations these genes display late-onset morphological changes pigment epithelium (RPE). To determine whether observed preceded by abnormal RPE function, we investigated its phagocytic function...
Abstract Mutations in the ubiquitously expressed pre-mRNA processing factor ( PRPF ) 31 gene, one of most common causes dominant form Retinitis Pigmentosa (RP), lead to a retina-specific phenotype. It is uncertain which retinal cell types are affected and animal models do not clearly present RP phenotype observed PRPF31 patients. Retinal organoids pigment epithelial (RPE) cells derived from human-induced pluripotent stem (iPSCs) provide potential opportunities for studying human -related RP....
Mutations in genes that produce proteins involved mRNA splicing, including pre-mRNA processing factors 3, 8, and 31 (PRPF3, 31), RP9, SNRNP200 are common causes of the late-onset inherited blinding disorder retinitis pigmentosa (RP). It is not known how mutations these ubiquitously expressed lead to retina-specific disease. To investigate pathogenesis RNA splicing factor forms RP, authors generated characterized retinal phenotypes Prpf3-T494M, Prpf8-H2309P knockin mice. The ultrastructure...
Analysis of one the vital functions retinal pigment epithelial (RPE) cells, phagocytosis spent aged distal fragments photoreceptor outer segments (POS) can be performed in vitro. Photoreceptor with stacks membranous discs containing phototransduction machinery are continuously renewed retina. Spent POS eliminated daily by RPE cells. Rodent, porcine/bovine and human cells recognize from various species a similar manner. To facilitate performing large series experiments little variability,...
Abstract Mutations of ubiquitous PRPF splicing factors represent the second cause retina-specific autosomic dominant retinitis pigmentosa. Prpf31 downregulation decreases phagocytosis mouse and human retinal pigment epithelial (RPE) cells, thus suggesting similar pathogenesis between species. With time, RPE ultrastructure shows signs cellular stress such as cytoplasmic vacuoles. To decipher primary origin -related deleterious processes we first confirmed gradual accumulation protein lipid...
Congenital cataracts are a major cause of bilateral visual impairment in childhood. We mapped the gene responsible for autosomal congenital cerulean to chromosome 2q33–35 four generation family Moroccan descent. The maximum lod score (7.19 at recombination fraction θ=0) was obtained marker D2S2208 near γ-crystallin (<i>CRYG</i>) cluster. Sequencing coding regions <i>CRYGA</i>, <i>B</i>, <i>C</i>, and <i>D</i> genes showed presence heterozygous C>A transversion exon 2 <i>CRYGD</i> that is...
αvβ5 integrin and Mer tyrosine kinase (MerTK) receptors reside at the apical surface of retinal pigment epithelium (RPE) in eye to promote diurnal, synchronised phagocytosis shed photoreceptor outer segment fragments (POS) that is critical for vision. Phagocytosis assays studying RPE cells culture have defined roles POS binding MerTK engulfment bound POS. Both thus far only been studied separately. It therefore unknown if activity independent function cells. This study investigates how...
Abstract In vitro differentiation of human pluripotent stem cells into functional retinal pigment epithelial (RPE) provides a potentially unlimited source for cell based reparative therapy age-related macular degeneration. Although the inherent pigmentation RPE have been useful to grossly evaluate efficiency and allowed manual isolation pigmented structures, accurate quantification automated has challenging. To address this issue, here we perform comprehensive antibody screening identify...
Among the myriad of existing tyrosine kinase receptors, TAM family—abbreviated from Tyro3, Axl, and Mer (MerTK)—has been extensively studied with an outstanding contribution team Prof. Greg Lemke. MerTK activity is implicated in a wide variety functions involving elimination apoptotic cells has recently linked to cancers, auto-immune diseases, atherosclerosis/stroke. In retina, required for circadian phagocytosis oxidized photoreceptor outer segments by retinal-pigment epithelial cells,...
alpha(v)beta(5)-Integrin is the sole integrin receptor at retinal pigment epithelium (RPE)-photoreceptor interface and promotes RPE phagocytic signaling to tyrosine kinase Mer (MerTK) once a day in response circadian photoreceptor shedding. Herein we identify novel role for alpha(v)beta(5)-integrin permanent RPE-photoreceptor adhesion that independent of alpha(v)beta(5)'s function phagocytosis. To compare wild-type beta(5)-integrin(-/-) mice, mechanically separated neural retina quantified...
In the eye, cells from retinal pigment epithelium (RPE) facing neurosensory retina exert several functions that are all crucial for long-term survival of photoreceptors (PRs) and vision. Among those, RPE phagocytose under a circadian rhythm photoreceptor outer segment (POS) tips constantly subjected to light rays oxidative attacks. The MerTK tyrosine kinase receptor is key element this phagocytic machinery required POS internalization. Recently, we showed cleavage its extracellular domain...
Our purpose was to investigate genes and molecular mechanisms involved in patients with Leber congenital amaurosis (LCA) model this type of LCA for drug screening. Fibroblasts from two unrelated clinically identified a yet undetermined gene mutation were reprogrammed pluripotency by retroviral transduction. These human induced pluripotent stem cells (hiPSCs) differentiated into neural (NSCs) that mimicked the tube stage retinal pigmented epithelial (RPE) could be targeted disease. A...