A5101960262- Retinal Development and Disorders
- Retinal Diseases and Treatments
- MicroRNA in disease regulation
- RNA regulation and disease
- Photoreceptor and optogenetics research
- CRISPR and Genetic Engineering
- Lipid metabolism and disorders
- Connexins and lens biology
- Cellular transport and secretion
- Genetic Associations and Epidemiology
- Retinal Imaging and Analysis
- Liver Disease Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Biological and pharmacological studies of plants
- Cholinesterase and Neurodegenerative Diseases
- Advanced biosensing and bioanalysis techniques
- Ferroptosis and cancer prognosis
- interferon and immune responses
- Retinal and Optic Conditions
- Cancer, Hypoxia, and Metabolism
- Chemical synthesis and alkaloids
- Ocular Disorders and Treatments
- Virus-based gene therapy research
- Circular RNAs in diseases
- Genetic and Kidney Cyst Diseases
Wenzhou Medical University
2016-2025
Affiliated Eye Hospital of Wenzhou Medical College
2016-2025
ShanghaiTech University
2024
State Key Laboratory of Ophthalmology
2017-2022
National Clinical Research Center for Digestive Diseases
2020
Institute for Stem Cell Biology and Regenerative Medicine
2019-2020
Fudan University Shanghai Cancer Center
2017
Purdue University West Lafayette
2015-2016
State Street (United States)
2016
University of Georgia
2016
Significance Because preschool children encounter fewer risks from environmental pressures, we propose that the condition of early-onset high myopia (EOHM) is driven by a genetic predisposition more than factors. In this study, recruited 18 familial trios to decipher using whole-exome sequencing. We identified cluster unique genes linked EOHM, as well mutations in reported genes. Notably, showed both rare inherited and de novo significantly contributed EOHM. Expression profiling ocular...
Retinitis pigmentosa (RP) is characterized by degeneration of the retinal photoreceptors and leading cause inherited blindness worldwide. Although few genes are known to autosomal recessive RP (arRP), a large proportion disease-causing remain be revealed. Here we report identification SLC7A14, potential cationic transporter, as novel gene linked arRP. Using exome sequencing direct screening 248 unrelated patients with arRP, find that mutations in SLC7A14 account for 2% cases We further...
Significance The polycistronic miR-183/96/182 cluster is highly expressed in various types of terminally differentiating sensory neurons, including photoreceptors. Although miR-182 single-knockout mice do not exhibit significant retinal architecture alterations photoreceptors, deletion miR-183 and miR-96 gives rise to severe defects cone maturation. Long-term follow-up analysis reveals that miR-183/96 ablation results progressive photoreceptor degeneration. Mechanistic studies demonstrate...
The microRNA cluster miR-183C, which includes miR-183 and two other genes, is critical for multiple sensory systems. In mouse retina, removal of this results in photoreceptor defects polarization, phototransduction, outer segment elongation. However, the individual roles three components are not clearly known. We studied separate role vivo.miR-183 knockout mice were generated using CRISPR/Cas9 genome-editing system. Electroretinography carried out to investigate changes retinal structures...
Retinal degeneration is often progressive. This feature has provided a therapeutic window for intervention that may extend functional vision in patients. Even though this approach feasible, few promising drug candidates are available. The scarcity of new drugs motivated research to discover novel compounds through different sources. One such example Schisandrin B (SchB), an active component isolated from the five-flavor fruit (Fructus Schisandrae) postulated traditional Chinese medicines...
Purpose: MicroRNA-182 (miR-182) is abundantly expressed in mammalian retinas; however, the association between miR-182 and retinal function remains unclear. In this study, we explored whether contributes to functional decline retinas using a depleted mouse. Methods: Electroretinogram (ERG) amplitudes at different ages were measured knockout (KO) mice. The thickness lamination of assessed color fundus camera high-resolution optical coherence tomography. Expression levels key...
Circular RNAs (circRNAs) represent a class of noncoding with wide expression pattern, and they constitute an important layer the genome regulatory network. To date, pattern potency circRNAs in retina, key part central nervous system, are not yet well understood. In this study, from five stages (E18.5, P1, P7, P14, P30) mouse retinal development were sequenced. A total 9,029 identified. Most expressed different specific signature, their patterns those host linear transcripts. Some could act...
ABSTRACT The miniature RNA‐guided endonuclease IscB, as the evolutionary progenitor of Cas9, is attracting increased attention for genome editing due to its compact size and suitability in vivo delivery. However, poor efficiency IscB eukaryotic cells presents a significant challenge widespread application precise site‐specific human editing. In this study, we employed structure‐guided rational design protein engineering optimize OgeuIscB, resulting identification enIscB‐F138R, which further...
The retinal degeneration 11 (rd11) mouse is a newly discovered, naturally occurring animal model with early photoreceptor dysfunction and rapid rod followed by cone degeneration. rd11 mice carry spontaneous mutation in the lysophosphatidylcholine acyltransferase 1 (Lpcat1) gene. Here, we evaluate whether gene replacement therapy using fast-acting tyrosine-capsid mutant AAV8 (Y733F) can arrest restore function this model.The (Y733F)-smCBA-Lpcat1 was delivered subretinally to postnatal day 14...
Ocular coloboma is a developmental structural defect of the eye that often occurs as complex ocular anomalies. However, its genetic etiology remains largely unexplored. Here we report identification mutation (c.331C>T, p.R111C) in IPO13 gene consanguineous family with coloboma, microphthalmia, and cataract by combination whole-exome sequencing homozygosity mapping. encodes an importin-B protein has been proven to be associated pathogenesis microphthalmia. We found Ipo13 was expressed cornea,...
Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree genetic, allelic, and phenotypic heterogeneity. CEP250 encodes C-Nap1 protein has been associated various phenotypes. Here, we report identification a mutation (c.562C>T, p.R188*) in consanguineous family nonsyndromic RP. To gain insights into molecular pathomechanism underlying defects functional relevance variants humans, conducted characterization variant using novel Cep250 knockin...
Age-related macular degeneration (AMD) is one of the major causes vision loss. Early AMD needs to be taken seriously, but causal effects lipid biomarkers on early remain unclear. In this study, two-sample Mendelian randomization (MR) analysis was performed systematically assess relationships between seven serum (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein (HDL-C), direct low-density (LDL-C), [Lp(a)], and triglycerides (TG)) risk AMD....
Degeneration of retinal photoreceptors is frequently observed in diverse ciliopathy disorders, and photoreceptor cilium gates the molecular trafficking between inner outer segment (OS). This study aims to generate a homozygous global Cep250 knockout (KO) mouse resulting phenotype.We used KO mice untargeted metabolomics uncover potential mechanisms underlying degeneration. Long-term follow-up studies using optical coherence tomography (OCT) electroretinography (ERG) were performed.OCT ERG...
Abstract Precursor messenger RNA (Pre-mRNA) splicing is an essential biological process in eukaryotic cells. Genetic mutations many spliceosome genes confer human eye diseases. Mutations the pre-mRNA factor, RP9 (also known as PAP1), predispose autosomal dominant retinitis pigmentosa (adRP) with early onset and severe vision loss. However, underlying molecular mechanisms of mutation causing photoreceptor degeneration remains fully unknown. Here, we utilize CRISPR/Cas9 system to generate both...
Previous study has identified SLC7A14 as a new causative gene of retinitis pigmentosa (RP). However, the role not been fully characterized. The goal this was to investigate biological features slc7a14 in zebrafish. To determine expression developing zebrafish, we performed situ hybridization (ISH) and quantitative real-time PCR. Morpholino knockdown overexpression experiments were zebrafish retinas. Immunostaining carried out observe structural changes. Visual motor responses (VMR)...
Abstract Adenosine diphosphate (ADP)‐ribosylation factor‐like 2 (ARL2) protein participates in a broad range of cellular processes and acts as mediator for mutant ARL2BP cilium‐associated retinitis pigmentosa HRG4 mitochondria‐related photoreceptor degeneration. However, ARL2 has not been linked to any human disease so far. Here, we identified de novo variant (c.44G > T, p.R15L) Chinese pedigree with MRCS (microcornea, rod‐cone dystrophy, cataract, posterior staphyloma) syndrome through...
Abundant retinal microRNA-183 cluster (miR-183C) has been reported to be a key player in photoreceptor development and functionality mice. However, whether there is protagonist this remains unclear. Here, we used mutant mouse model study the role of miR-96, member miR-183C, functionality.The mature miR-96 sequence was removed using CRISPR/Cas9 genome-editing system. Electroretinogram (ERG) optical coherence tomography (OCT) investigated changes structure function retinas. Immunostaining...
Summary Targeting genes to specific neuronal or glial cell types is valuable both for understanding and repairing brain circuits. Adeno-associated viral vectors (AAVs) are frequently used gene delivery, but targeting expression a challenge. We created library of 230 AAVs, each with different synthetic promoter designed using four independent strategies. show that ~11% these AAVs specifically target in the mouse retina, brain, non-human primate retina vivo , human vitro . demonstrate...
Adenine base editors (ABEs) are genome-editing tools that have been harnessed to introduce precise A•T G•C conversion. The discovery of split genes revealed all introns contain two highly conserved dinucleotides, canonical "AG" (acceptor) and "GT" (donor) splice sites. ABE can directly edit acceptor sites the adenine (A) base, leading aberrant gene splicing, which may be further adopted remodel splicing. However, spliced isoforms triggered with not well explored. To address it, we initially...
Purpose: Accumulating evidence has demonstrated that excessive immunoreaction plays a prominent role in the pathogenesis of dry AMD. Toll-like receptor 3 (TLR3) can be activated by double-stranded (ds)RNA retinal pigment epithelia and trigger an innate immunity-mediated inflammatory response. However, its photoreceptor cells, effectors AMD geographic atrophy, remains unclear. Methods: The expression TLR3 was examined mouse retina murine cell line (661W). Retinal structure, function, death...
Neurodegenerative retinal diseases such as retinitis pigmentosa are serious disorders that may cause irreversible visual impairment. Ferroptosis is a novel type of programmed cell death, and the involvement ferroptosis in degeneration still unclear. This study aimed to investigate related genes mice model induced by light damage.A public dataset GSE10528 deriving from Gene Expression Omnibus database was analyzed identify differentially expressed (DEGs). set enrichment analysis between...