Molecular Vision最新文献

{"title":"Encephalopsin (OPN3) is required for normal refractive development and the GO/GROW response to induced myopia.","authors":"Courtney Linne, Khine Yin Mon, Shane D'Souza, Heonuk Jeong, Xiaoyan Jiang, Dillon M Brown, Kevin Zhang, Shruti Vemaraju, Kazuo Tsubota, Toshihide Kurihara, Machelle T Pardue, Richard A Lang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Myopia, or nearsightedness, is the most common form of refractive error and is increasing in prevalence. While significant efforts have been made to identify genetic variants that predispose individuals to myopia, these variants are believed to account for only a small portion of the myopia prevalence, leading to a feedback theory of emmetropization, which depends on the active perception of environmental visual cues. Consequently, there has been renewed interest in studying myopia in the context of light perception, beginning with the opsin family of G-protein coupled receptors (GPCRs). Refractive phenotypes have been characterized in every opsin signaling pathway studied, leaving only Opsin 3 (OPN3), the most widely expressed and blue-light sensing noncanonical opsin, to be investigated for function in the eye and refraction.</p><p><strong>Methods: </strong><i>Opn3</i> expression was assessed in various ocular tissues using an Opn3eGFP reporter. Weekly refractive development in <i>Opn3</i> retinal and germline mutants from 3 to 9 weeks of age was measured using an infrared photorefractor and spectral domain optical coherence tomography (SD-OCT). Susceptibility to lens-induced myopia was then assessed using skull-mounted goggles with a -30 diopter experimental and a 0 diopter control lens. Mouse eye biometry was similarly tracked from 3 to 6 weeks. A myopia gene expression signature was assessed 24 h after lens induction for germline mutants to further assess myopia-induced changes.</p><p><strong>Results: </strong><i>Opn3</i> was found to be expressed in a subset of retinal ganglion cells and a limited number of choroidal cells. Based on an assessment of <i>Opn3</i> mutants, the OPN3 germline, but not retina conditional <i>Opn3</i> knockout, exhibits a refractive myopia phenotype, which manifests in decreased lens thickness, shallower aqueous compartment depth, and shorter axial length, atypical of traditional axial myopias. Despite the short axial length, <i>Opn3</i> null eyes demonstrate normal axial elongation in response to myopia induction and mild changes in choroidal thinning and myopic shift, suggesting that susceptibility to lens-induced myopia is largely unchanged. Additionally, the <i>Opn3</i> null retinal gene expression signature in response to induced myopia after 24 h is distinct, with opposing <i>Ctgf</i>, <i>Cx43</i>, and <i>Egr1</i> polarity compared to controls.</p><p><strong>Conclusions: </strong>The data suggest that an OPN3 expression domain outside the retina can control lens shape and thus the refractive performance of the eye. Prior to this study, the role of <i>Opn3</i> in the eye had not been investigated. This work adds OPN3 to the list of opsin family GPCRs that are implicated in emmetropization and myopia. Further, the work to exclude retinal OPN3 as the contributing domain in this refractive phenotype is unique and suggests a distinct mechanism when compared to other opsins.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"29 ","pages":"39-57"},"PeriodicalIF":2.2,"publicationDate":"2023-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/f2/mv-v29-39.PMC10243678.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9602656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry.","authors":"Tamar Ben Yosef,&nbsp;Eyal Banin,&nbsp;Elana Chervinsky,&nbsp;Stavit A Shalev,&nbsp;Rina Leibu,&nbsp;Eedy Mezer,&nbsp;Ygal Rotenstreich,&nbsp;Nitza Goldenberg-Cohen,&nbsp;Shirel Weiss,&nbsp;Muhammad Imran Khan,&nbsp;Daan M Panneman,&nbsp;Rebekkah J Hitti-Malin,&nbsp;Chen Weiner,&nbsp;Susanne Roosing,&nbsp;Frans P M Cremers,&nbsp;Eran Pras,&nbsp;Dinah Zur,&nbsp;Hadas Newman,&nbsp;Iris Deitch,&nbsp;Dror Sharon,&nbsp;Miriam Ehrenberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>This study sought to describe the phenotype frequency and genetic basis of inherited retinal diseases (IRDs) among a nationwide cohort of Israeli Jewish patients of Ethiopian ancestry.</p><p><strong>Methods: </strong>Patients' data-including demographic, clinical, and genetic information-were obtained through members of the Israeli Inherited Retinal Disease Consortium (IIRDC). Genetic analysis was performed by either Sanger sequencing for founder mutations or next-generation sequencing (targeted next-generation sequencing or whole-exome sequencing).</p><p><strong>Results: </strong>Forty-two patients (58% female) from 36 families were included, and their ages ranged from one year to 82 years. Their most common phenotypes were Stargardt disease (36%) and nonsyndromic retinitis pigmentosa (33%), while their most common mode of inheritance was autosomal recessive inheritance. Genetic diagnoses were ascertained for 72% of genetically analyzed patients. The most frequent gene involved was <i>ABCA4</i>. Overall, 16 distinct IRD mutations were identified, nine of which are novel. One of them, <i>ABCA4</i>-c.6077delT, is likely a founder mutation among the studied population.</p><p><strong>Conclusions: </strong>This study is the first to describe IRDs' phenotypic and molecular characteristics in the Ethiopian Jewish community. Most of the identified variants are rare. Our findings can help caregivers with clinical and molecular diagnosis and, we hope, enable adequate therapy in the near future.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"29 ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/63/mv-v29-1.PMC10243676.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9603137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The retina-specific basigin isoform does not induce IL-6 expression in mouse monocytes.","authors":"Abigail D Solstad,&nbsp;Josephine M Brown,&nbsp;Judith D Ochrietor","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Basigin gene products are positioned on adjacent cell types in the neural retina and are thought to compose a lactate metabolon important for photoreceptor cell function. The Ig0 domain of basigin isoform 1 (basigin-1) is highly conserved throughout evolution, which suggests a conserved function. It has been suggested that the Ig0 domain has proinflammatory properties, and it is hypothesized to interact with basigin isoform 2 (basigin-2) for cell adhesion and lactate metabolon formation. Therefore, the purpose of the present study was to determine whether the Ig0 domain of basigin-1 binds to basigin-2 and whether the region of the domain used for binding is also used to stimulate interleukin-6 (IL-6) expression.</p><p><strong>Methods: </strong>Binding was assessed using recombinant proteins corresponding to the Ig0 domain of basigin-1 and endogenously expressed basigin-2 from mouse neural retina and brain protein lysates. The proinflammatory properties of the Ig0 domain were analyzed with exposure of the recombinant proteins to the mouse monocyte RAW 264.7 cell line and subsequent measurement of the IL-6 concentration in the culture medium via enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The data indicate that the Ig0 domain interacts with basigin-2 through a region within the amino half of the domain and that the Ig0 domain does not stimulate the expression of IL-6 in mouse cells in vitro.</p><p><strong>Conclusions: </strong>The Ig0 domain of basigin-1 binds to basigin-2 in vitro. In addition, contrary to previous reports, there was no evidence that the Ig0 domain potentiates IL-6 expression in a mouse monocyte cell line in vitro. However, it is possible that the Ig0 domain stimulates the expression of proinflammatory cytokines other than IL-6, or that the potential involvement of the Ig0 domain of basigin-1 in the acute inflammatory response is dependent on species.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"29 ","pages":"13-24"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/73/mv-v29-13.PMC10243675.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9600053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>USH2A</i> mutational spectrum causing syndromic and non-syndromic retinal dystrophies in a large cohort of Mexican patients.","authors":"Vianey Ordoñez-Labastida,&nbsp;Oscar F Chacon-Camacho,&nbsp;Victor R Lopez-Rodriguez,&nbsp;Juan C Zenteno","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the <i>USH2A</i> gene are the leading cause of both non-syndromic autosomal recessive retinitis pigmentosa (RP) and Usher syndrome, a syndromic form of RP characterized by retinal dystrophy and sensorineural hearing loss. To contribute to the expansion of the <i>USH2A</i>-related molecular spectrum, the results of genetic screening in a large cohort of Mexican patients are presented.</p><p><strong>Methods: </strong>The study population comprised 61 patients with a clinical diagnosis of either non-syndromic RP (n = 30) or Usher syndrome type 2 (USH2; n = 31) who were demonstrated to carry biallelic pathogenic variants in <i>USH2A</i> in a three-year period. Genetic screening was performed either by gene panel sequencing or by exome sequencing. A total of 72 available first- or second-degree relatives were also genotyped for familial segregation of the identified variants.</p><p><strong>Results: </strong>The <i>USH2A</i> mutational spectrum in RP patients included 39 distinct pathogenic variants, most of them of the missense type. The most common RP-causing variants were p.Cys759Phe (c.2276G>T), p.Glu767Serfs*21 (c.2299delG), and p.Cys319Tyr (c.956G>A), which together accounted for 25% of all RP variants. Novel <i>USH2A</i> mutations included three nonsense, two missense, two frameshift, and one intragenic deletion. The <i>USH2A</i> mutational spectrum in USH2 patients included 26 distinct pathogenic variants, most of them of the nonsense and frameshift types. The most common Usher syndrome-causing variants were p.Glu767Serfs*21 (c.2299delG), p.Arg334Trp (c.1000C>T), and c.12067-2A>G), which together accounted for 42% of all USH2-related variants. Novel Usher syndrome <i>USH2A</i> mutations included six nonsense, four frameshift, and two missense mutations. The c.2299delG mutation was associated with a common haplotype for SNPs located in exons 2-21 of <i>USH2A</i>, indicating a founder mutation effect.</p><p><strong>Conclusions: </strong>Our work expands the <i>USH2A</i> mutational profile by identifying 20 novel pathogenic variants causing syndromic and non-syndromic retinal dystrophy. The prevalent c.2299delG allele is shown to arise from a founder effect. Our results emphasize the usefulness of molecular screening in underrepresented populations for a better characterization of the molecular spectrum of common monogenic diseases.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"29 ","pages":"31-38"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/df/mv-v29-31.PMC10243674.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9602654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basement membrane regeneration and TGF-β1 expression in rabbits with corneal perforating injury.","authors":"Na Meng,&nbsp;Jinling Wu,&nbsp;Jingjing Chen,&nbsp;Yuqing Luo,&nbsp;Luxing Xu,&nbsp;Xia Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the relationship between basement membrane (BM) regeneration and the spatiotemporal expression of TGF-β1 during wound healing in rabbits with corneal perforating injury.</p><p><strong>Methods: </strong>Forty-two rabbits were randomly allocated into 7 experimental groups, with 6 rabbits per group at each time point. The central cornea of the left eye was injured with 2.0 mm trephine to establish the perforating injury model. Six rabbits that received no treatment were used as controls. The cornea was evaluated at 3 days, 1-3 weeks, and 1-3 months after injury with a slit lamp for haze levels. Real-time quantitative polymerase chain reaction (qRT-PCR) was performed to quantify the relative expression of TGF-β1 and α-SMA mRNA. Immunofluorescence (IF) was used to assess TGF-β1 and alpha-smooth actin (α-SMA) expression and localization. BM regeneration was assessed using transmission electron microscopy (TEM).</p><p><strong>Results: </strong>After injury, dense haze appeared at 1 month and then gradually faded. The relative expression of TGF-β1 mRNA peaked at 1 week and then decreased until 2 months. The relative α-SMA mRNA expression reached its peak at 1 week, then reached a small peak again at 1 month. IF results showed that TGF-β1 was initially detected in the fibrin clot at 3 days and then in the entire repairing stroma at 1 week. TGF-β1 localization gradually diminished from the anterior region to the posterior region at 2 weeks to 1 month, and it was nearly absent at 2 months. The myofibroblast marker α-SMA was observed in the entire healing stroma at 2 weeks. Localization of α-SMA gradually disappeared from the anterior region at 3 weeks to 1 month, remaining only in the posterior region at 2 months and disappearing at 3 months. Defective epithelial basement membrane (EBM) was first detected at 3 weeks after injury, then gradually repaired, and was nearly regenerated at 3 months. A thin and uneven Descemet's membrane (DM) was initially detected at 2 months after injury, then gradually regenerated to some extent, but remained abnormal at 3 months.</p><p><strong>Conclusions: </strong>In the rabbit corneal perforating injury model, EBM regeneration was observed earlier than DM. At 3 months, complete EBM regeneration was observed, while the regenerated DM was still defective. TGF-β1 was distributed throughout the entire wound area in the early stages and then decreased from the anterior to the posterior region. α-SMA exhibited a similar temporospatial expression to TGF-β1. EBM regeneration may play a key role in low expression of TGF-β1 and α-SMA in the anterior stroma. Meanwhile, incomplete DM regeneration may contribute to the sustained expression of TGF-β1 and α-SMA in the posterior stroma.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"29 ","pages":"58-67"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3e/87/mv-v29-58.PMC10243679.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9600055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel partial deletion of <i>STS</i> associated with pre-Descemet corneal dystrophy and X-linked ichthyosis.","authors":"Dominic Williams,&nbsp;Onyinye Onyia,&nbsp;Doug D Chung,&nbsp;Artak Kirakosyan,&nbsp;Anna Hovakimyan,&nbsp;Carter Payne,&nbsp;Majid Moshirfar,&nbsp;Anthony J Aldave","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Pre-Descemet corneal dystrophy (PDCD) with X-linked ichthyosis (XLI) is associated with mutations in or deletions of the steroid sulfatase gene (<i>STS</i>). As only three cases of genetically confirmed PDCD associated with XLI have been reported, we sought to expand our understanding of the genetic basis of PDCD by screening <i>STS</i> in two previously unreported families.</p><p><strong>Materials and methods: </strong>The affected individuals underwent cutaneous and slit-lamp examinations. Saliva samples collected from each affected individual served as a source of DNA for the amplification of the 10 coding exons of <i>STS</i> and flanking DNA markers.</p><p><strong>Results: </strong>The slit-lamp examination of three affected men (two of whom were brothers) from two families revealed bilateral punctate posterior corneal stromal opacities anterior to the Descemet membrane. Cutaneous examination demonstrated dry, coarse, scaly ichthyotic changes characteristic of XLI in all individuals. Genetic examination of the <i>STS</i> locus on the X chromosome in Case 1 revealed a deletion that spanned across DNA markers DXS1130-DXS237, which includes all the coding exons (exons 1-10) of <i>STS</i>. Genetic screening of Cases 2 and 3 revealed a partial deletion of the <i>STS</i> locus involving exons 1-7 and flanking DNA marker DXS1130 on the X chromosome.</p><p><strong>Conclusions: </strong>PDCD with XLI may be associated with either partial or complete deletion of <i>STS</i>. Despite the identification of point mutations, partial deletion, and complete deletion of <i>STS</i> in different affected families reported to date, there was no apparent difference in the affected phenotype between the families, suggesting that the identified variants likely all resulted in loss of function of steroid sulfatase.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"29 ","pages":"25-30"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/44/45/mv-v29-25.PMC10243677.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9603136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological, biochemical, and transcriptomic characterization of iPSC-derived human RPE cells from normal and Smith-Lemli-Opitz syndrome patients.","authors":"Michael H Farkas, Lara A Skelton, Sriganesh Ramachandra-Rao, Elizabeth Au, Steven J Fliesler","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"28 ","pages":"394-411"},"PeriodicalIF":1.8,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/b8/mv-v28-394.PMC9744241.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel homozygous mutations in the transcription factor <i>NRL</i> cause non-syndromic retinitis pigmentosa.","authors":"Mohammed E El-Asrag, Marta Corton, Martin McKibbin, Almudena Avila-Fernandez, Moin D Mohamed, Fiona Blanco-Kelly, Carmel Toomes, Chris F Inglehearn, Carmen Ayuso, Manir Ali","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To describe the clinical phenotype and genetic basis of non-syndromic retinitis pigmentosa (RP) in one family and two sporadic cases with biallelic mutations in the transcription factor neural retina leucine zipper (<i>NRL)</i>.</p><p><strong>Methods: </strong>Exome sequencing was performed in one affected family member. Microsatellite genotyping was used for haplotype analysis. PCR and Sanger sequencing were used to confirm mutations in and screen other family members where they were available. The SMART tool for domain prediction helped us build the protein schematic diagram.</p><p><strong>Results: </strong>For family MM1 of Pakistani origin, whole-exome sequencing and microsatellite genotyping revealed homozygosity on chromosome 14 and identified a homozygous stop-loss mutation in <i>NRL</i>, NM_006177.5: c.713G>T, p.*238Lext57, which is predicted to add an extra 57 amino acids to the normal protein chain. The variant segregated with disease symptoms in the family. For case RP-3051 of Spanish ancestry, clinical exome sequencing focusing on the morbid genome highlighted a homozygous nonsense mutation in <i>NRL</i>, c.238C>T, p.Gln80*, as the most likely disease candidate. For case RP-1553 of Romanian ethnicity, targeted-exome sequencing of 73 RP/LCA genes identified a homozygous nonsense mutation in <i>NRL</i>, c.544C>T, p.Gln182*. The variants were either rare or absent in the gnomAD database.</p><p><strong>Conclusions: </strong><i>NRL</i> mutations predominantly cause dominant retinal disease, but there have been five published reports of mutations causing recessive disease. Here, we present three further examples of recessive RP due to <i>NRL</i> mutations. The phenotypes observed are consistent with those in the previous reports, and the observed mutation types and distribution further confirm distinct patterns for variants in <i>NRL</i> causing recessive and dominant diseases.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"28 ","pages":"48-56"},"PeriodicalIF":1.8,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET imaging of retinal inflammation in mice exposed to blue light using [¹⁸F]-DPA-714.","authors":"Yuan Chen,&nbsp;Yixiang Zhou,&nbsp;Xue Zhu,&nbsp;Ge Yan,&nbsp;Donghui Pan,&nbsp;Lizhen Wang,&nbsp;Min Yang,&nbsp;Ke Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Positron emission tomography (PET) is widely used in high-precision imaging, which may provide a simple and noninvasive method for the detection of pathology and therapeutic effects. [¹⁸F]-DPA-714 is a second-generation translocator protein (TSPO) positron emission tomography radiotracer that shows great promise in a model of neuroinflammation. In this study, [¹⁸F]-DPA-714 micro-PET imaging was used to evaluate retinal inflammation in mice exposed to blue light, a well-established model of age-related macular degeneration (AMD) for molecular mechanism research and drug screening.</p><p><strong>Methods: </strong>C57BL/6J melanized mice were subjected to 10,000, 15,000, and 20,000 lux blue light for 5 days (8 h/day) to develop the retinal injury model, and the structure and function of the retina were assessed using hematoxylin-eosin (HE) staining, electroretinography (ERG), and terminal-deoxynucleotidyl transferase (TdT)-mediated nick-end labeling (TUNEL) immunostaining. Then, [¹⁸F]-DPA-714 was injected approximately 100 μCi through each tail vein, and static imaging was performed 1 h after injection. Finally, the mice eyeballs were collected for biodistribution and immune analysis.</p><p><strong>Results: </strong>The blue light exposure significantly destroyed the structure and function of the retina, and the uptake of [¹⁸F]-DPA-714 in the retinas of the mice exposed to blue light were the most significantly upregulated, which was consistent with the biodistribution data. In addition, the immunohistochemical, western blot, and immunofluorescence data showed an increase in microglial TSPO expression.</p><p><strong>Conclusions: </strong>[¹⁸F]-DPA-714 micro-PET imaging might be a good method for evaluating early inflammatory status during retinal pathology.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"28 ","pages":"507-515"},"PeriodicalIF":2.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/43/d4/mv-v28-507.PMC10115360.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9380332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The long noncoding RNA MALAT1/microRNA-598-3p axis regulates the proliferation and apoptosis of retinoblastoma cells through the PI3K/AKT pathway.","authors":"Xiaoli Lin,&nbsp;Xionggao Huang,&nbsp;Ling Wang,&nbsp;Weixian Liu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>This study was designed to dissect the role of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in retinoblastoma (RB) and its underlying mechanism.</p><p><strong>Methods: </strong>Gain- and loss-of-function experiments were adopted to explore the effects of MALAT1 and microRNA (miR)-598-3p on the biologic behaviors of RB cells. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of MALAT1 and miR-598-3p in Y79 and HXO-RB44 cells. The proliferation of RB cells was determined with the cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) staining. Flow cytometry was employed for the measurement of the apoptotic rate, western blotting for examination of the expression of apoptosis-related proteins (Bax and Bcl-2) and phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) pathway-related factors (PI3K, AKT, p-PI3K, and p-AKT), and the luciferase reporter assay for assessment of the interaction between MALAT1 and miR-598-3p.</p><p><strong>Results: </strong>High expression of MALAT1 and low expression of miR-598-3p were noticed in Y79 and HXO-RB44 cells. MALAT1 upregulation or miR-598-3p downregulation facilitated RB cell proliferation and inhibited cell apoptosis, as evidenced by the increased proliferation rate and Bcl-2 expression, as well as diminished Bax expression and apoptotic rate, in the RB cells after transfection with pcDNA3.1-MALAT1 or miR-598-3p inhibitor. MALAT1 bound to and negatively regulated miR-598-3p. The PI3K/AKT pathway activation occurred with MALAT1 overexpression. MALAT1 promoted RB cell proliferation and repressed cell apoptosis by repressing miR-598-3p to activate the PI3K/AKT pathway.</p><p><strong>Conclusions: </strong>MALAT1 repressed miR-598-3p to activate the PI3K/AKT pathway, thus facilitating cell proliferation and inhibiting cell apoptosis in RB.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"28 ","pages":"269-279"},"PeriodicalIF":2.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/80/mv-v28-269.PMC9514550.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}