Search results for "IGM"
showing 10 items of 1928 documents
Usherin defects lead to early-onset retinal dysfunction in zebrafish
2018
Mutations in USH2A are the most frequent cause of Usher syndrome and autosomal recessive nonsyndromic retinitis pigmentosa. To unravel the pathogenic mechanisms underlying USH2A-associated retinal degeneration and to evaluate future therapeutic strategies that could potentially halt the progression of this devastating disorder, an animal model is needed. The available Ush2a knock-out mouse model does not mimic the human phenotype, because it presents with only a mild and late-onset retinal degeneration. Using CRISPR/Cas9-technology, we introduced protein-truncating germline lesions into the zebrafish ush2a gene (ush2a(rmc1): c.2337_2342delinsAC; p.Cys780GlnfsTer32 and ush2a(b1245): c.15520_…
Primary Cilium-Mediated Retinal Pigment Epithelium Maturation Is Disrupted in Ciliopathy Patient Cells
2018
SUMMARY Primary cilia are sensory organelles that protrude from the cell membrane. Defects in the primary cilium cause ciliopathy disorders, with retinal degeneration as a prominent phenotype. Here, we demonstrate that the retinal pigment epithelium (RPE), essential for photoreceptor development and function, requires a functional primary cilium for complete maturation and that RPE maturation defects in ciliopathies precede photoreceptor degeneration. Pharmacologically enhanced ciliogenesis in wild-type induced pluripotent stem cells (iPSC)-RPE leads to fully mature and functional cells. In contrast, ciliopathy patient-derived iPSC-RPE and iPSC-RPE with a knockdown of ciliary-trafficking pr…
Generation of an inducible RPE-specific Cre transgenic-mouse line.
2018
The retinal pigment epithelium (RPE) is an epithelial monolayer in the back of the vertebrate eye. RPE dysfunction is associated with retinal degeneration and blindness. In order to fully understand how dysregulation affects visual function, RPE-specific gene knockouts are indispensable. Since the currently available RPE-specific Cre recombinases show lack of specificity or poor recombination, we sought to generate an alternative. We generated a tamoxifen-inducible RPE-specific Cre transgenic mouse line under transcriptional control of an RPE-specific Tyrosinase enhancer. We characterized the Cre-mediated recombinant expression by crossing our RPE-Tyrosinase-CreErT2 mouse line with the tdTo…
Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and …
2020
The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELIS…
Nutraceutical Supplementation Ameliorates Visual Function, Retinal Degeneration, and Redox Status in rd10 Mice
2021
Background: Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive degeneration of photoreceptor cells. Ocular redox status is altered in RP suggesting oxidative stress could contribute to their progression. In this study, we investigated the effect of a mixture of nutraceuticals with antioxidant properties (NUT) on retinal degeneration in rd10 mice, a model of RP. Methods: NUT was orally administered to rd10 mice from postnatal day (PD) 9 to PD18. At PD18 retinal function and morphology were examined by electroretinography (ERG) and histology including TUNEL assay, immunolabeling of microglia, Müller cells, and poly ADP ribose polymers. Retinal r…
DICER- and MMSET-catalyzed H4K20me2 recruits the nucleotide excision repair factor XPA to DNA damage sites
2017
The endoribonuclease DICER facilitates chromatin decondensation during lesion recognition following UV exposure. Chitale and Richly show that DICER mediates the recruitment of the methyltransferase MMSET, which catalyzes the dimethylation of histone H4 at lysine 20 and facilitates the recruitment of the nucleotide excision repair factor XPA.
Oral manifestations, salivary flow rates and Candida species in Thai HIV-infected patients
2019
Background Effects of various Highly Active Antiretroviral Therapy (HAART) regimens on oral heath are unclear. Objectives: We aimed to evaluate effects of HAART on oral manifestations, salivary flow rates (SFR) and Candida species in HIV-infected patients who took mostly non-protease inhibitor-based HAART regimens. Material and methods A cross-sectional study was performed on HIV-infected patients taking and never taken HAART who attended Thai Red Cross AIDS Research Centre (n = 48). Non-HIV subjects were recruited as control (n = 20). Oral conditions and salivary flow rates were evaluated using oral examination and measurement of unstimulated and stimulated saliva. In addition, Candida col…
Early life infection and host senescence
2018
IF 3.224 (2017); International audience; Advanced age is often associated with a chronic inflammatory status and inflammatory diseases. It has been suggested that exposure to infectious agents that stimulate the inflammatory response at early ages might have carry over effects in terms of accelerated senescence and increased mortality at late ages. However, not all pathogens and parasites have pro-inflammatory effects. In particular, parasitic nematodes have been shown to dampen the inflammatory response and to prevent or alleviate the symptoms of inflammatory diseases. We, therefore, tentatively predicted that early infection with a parasite that has anti-inflammatory properties might post…
The Sigma-1 Receptor at the Crossroad of Proteostasis, Neurodegeneration, and Autophagy.
2020
Neurodegenerative diseases are linked to dysfunctional proteostasis and disturbed autophagy. Here, we discuss how the sigma-1 receptor (Sig-1R) may act at the intersection of this interaction, as loss-of-function mutations of this unique chaperone are associated with defective autophagy and its pharmacological activation induces autophagic activity.
Genetic 3’UTR variation is associated with human pigmentation characteristics and sensitivity to sunlight
2017
Sunlight exposure induces signalling pathways leading to the activation of melanin synthesis and tanning response. MicroRNAs (miRNAs) can regulate the expression of genes involved in pigmentation pathways by binding to the complementary sequence in their 3'untranslated regions (3'UTRs). Therefore, 3'UTR SNPs are predicted to modify the ability of miRNAs to target genes, resulting in differential gene expression. In this study, we investigated the role in pigmentation and sun-sensitivity traits, as well as in melanoma susceptibility, of 38 different 3'UTR SNPs from 38 pigmentation-related genes. A total of 869 individuals of Spanish origin (526 melanoma cases and 343 controls) were analysed.…