Molecular Vision最新文献

{"title":"Clinical and genetic studies of 17 Han Chinese pedigrees and 31 sporadic patients with blepharophimosis-ptosis-epicanthus inversus syndrome.","authors":"Yuan Wang,&nbsp;Qian Wu,&nbsp;Wenhong Cao,&nbsp;Lijuan Huang,&nbsp;Wen Liu,&nbsp;Cheng Li,&nbsp;Ningdong Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the molecular pathogenesis of a large group of Han Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), and to evaluate the correlation between the phenotype and genotype for these patients.</p><p><strong>Methods: </strong>Seventy-six affected individuals, including 45 patients from 17 pedigrees and 31 sporadic patients, were recruited with their family members. All participants underwent complete clinical examinations and were classified as having type I or II based on whether they had premature ovarian failure. The patients' genomic DNA was extracted. A genetic test was performed with direct sequencing of the coding regions of the <i>forkhead transcriptional factor 2</i> (<i>FOXL2</i>) gene. Variations were analyzed using online databases and programs. Genotype-phenotype correction was investigated.</p><p><strong>Results: </strong>Seventy-six affected and 75 unaffected individuals underwent clinical evaluations and genetic testing. Only one family was diagnosed with type I; the others could not be classified because of a lack of female patients or a definite history of premature ovarian failure. Twenty-seven variations were identified, including 12 novel and 15 previously reported variations. Six variations were detected repeatedly in different nonconsanguineous pedigrees. Four indel variations, located in the alanine/proline-rich region of the <i>FOXL2</i> gene, presented with a relatively higher frequency. Two rare double variations were detected in two sporadic patients. <i>FOXL2</i> gene variations were not detected in five sporadic patients. The phenotype varied among different families and patients, although they carried the same variations.</p><p><strong>Conclusions: </strong>We identified 12 novel variations in the <i>FOXL2</i> gene that would expand the spectrum of the <i>FOXL2</i> variation database. In addition, we found that the alanine/proline-rich region is a variation hotspot in the <i>FOXL2</i> gene. The genotype-phenotype correlation is not easy to establish due to clinical and genetic heterogeneity.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/98/1b/mv-v28-352.PMC9603904.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10404763","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":"TNFAIP3 is anti-inflammatory in the retinal vasculature.","authors":"Li Liu,&nbsp;Youde Jiang,&nbsp;Jena J Steinle","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether tumor necrosis factor alpha-induced protein 3 (TNFAIP3) regulates inflammatory and permeability proteins in the retinal vasculature.</p><p><strong>Methods: </strong>We used retinal lysates from type 1 diabetic mice and endothelial cell-specific exchange protein for cAMP 1 (Epac1) knockout mice to determine the protein levels of TNFAIP3. We also treated retinal endothelial cells (RECs) in normal (5 mM) and high (25 mM) glucose with an Epac1 agonist or with TNFAIP3 siRNA. We performed western blotting for TNFAIP3 and inflammatory and permeability proteins after treatment. TNFAIP3 siRNA was used only in cells grown in high glucose. Immunostaining was performed for localization of ZO-1 and tight junction protein 1.</p><p><strong>Results: </strong>TNFAIP3 was reduced in the diabetic retinas and the retinas of the Epac1 conditional knockout mice. The Epac1 agonist increased TNFAIP3 levels in RECs grown in high glucose. Reduction of TNFAIP3 with siRNA led to increased levels of tumor necrosis factor alpha (TNFα) and phosphorylation of nuclear factor kappa beta (NF-kB), while decreasing occludin and zonula occludens 1 (ZO-1) protein levels and inhibitory kappa beta kinase (IkB) phosphorylation. Tumor receptor-associated factor 6 (TRAF6) levels were increased above high glucose levels.</p><p><strong>Conclusions: </strong>TNFAIP3 serves as an anti-inflammatory factor in the retinal vasculature. Epac1 regulates TNFAIP3. TNFAIP3 may offer a new mechanism for regulating inflammation and permeability in the retinal vasculature.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/62/f6/mv-v28-124.PMC9352365.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9703811","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":"Epac1 and PKA agonists inhibit ROS to reduce NLRP3 inflammasome proteins in retinal endothelial cells.","authors":"Li Liu,&nbsp;Youde Jiang,&nbsp;Jena J Steinle","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Reactive oxygen species (ROS) activate inflammatory pathways in several organs, including the retina. More recent work has shown that ROS activate the NOD-like receptor protein 3 (NLRP3) inflammasome pathway proteins. We recently showed that the exchange protein activated by cAMP 1 (Epac1) and protein kinase A (PKA) regulates NLRP3 proteins in the retina. Our goal was to determine whether Epac1 and PKA reduce ROS and NLRP3 inflammasome proteins.</p><p><strong>Methods: </strong>We used human primary retinal endothelial cells (RECs) grown in normal glucose (5 mM) and stimulated in normal glucose with hydrogen peroxide (H₂O₂) to induce ROS and measured NLRP3 pathway proteins. In some groups, we treated cells with an Epac1 or a PKA agonist in addition to H₂O₂ treatment to determine whether Epac1 and PKA reduced ROS and induced NLRP3 pathway proteins.</p><p><strong>Results: </strong>The data showed that 500 µM H₂O₂ was the optimal dose to increase ROS in RECs. In RECs treated with H₂O₂, NLRP3 pathway proteins were increased, which were significantly reduced by cotreatment with PKA or Epac1 agonists. H₂O₂ significantly increased NIMA-related kinase 7 (Nek7) and purinergic 2X7 receptor 7 (P2X7) levels, which were blocked by Epac1 and PKA agonists.</p><p><strong>Conclusions: </strong>Taken together, these data suggest that Epac1 and PKA reduce retinal inflammation through the reduced ROS-induced activation of NLRP3 pathway proteins.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/3f/55/mv-v28-500.PMC10115359.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9380327","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":"A five-year follow-up of <i>ABCA4</i> carriers showing deterioration of retinal function and increased structural changes.","authors":"Ulrika Kjellström,&nbsp;Sten Andréasson","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether the reduced retinal function and morphological retinal changes previously demonstrated in <i>ABCA4</i> carriers had remained stationary or had deteriorated over time at 5-year follow-up to further explore if carriers of an autosomal recessive trait also express a weak phenotype, although this is not expected for an autosomal recessive disorder.</p><p><strong>Methods: </strong>Thirteen <i>ABCA4</i> carriers from a previous study that included parents to patients with well known genetically verified <i>ABCA4</i>-associated retinal degenerations were reexamined 5 years after the initial examination. As novel genes and new variants in already established genes are continuously reported, all subjects underwent renewed genetic testing with a next-generation sequencing (NGS) panel that included 288 genes associated with retinal dystrophies and an analysis of deep intronic mutations and copy number variations in the <i>ABCA4</i> gene. Moreover, to evaluate any changes in retinal function and/or structure over time, clinical reassessment with Goldmann perimetry, visual acuity testing, fundus photography, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal ERG (mfERG) were performed 5 years after the initial investigation. The values of the ffERG parameters were compared between the two time points (the measurements obtained in the initial study versus the measurements at 5-year follow-up) and with the controls. The mfERG results of the carriers were compared with those of the controls.</p><p><strong>Results: </strong>The renewed genetic testing confirmed the previously established <i>ABCA4</i> mutations but also revealed the hypomorph <i>ABCA4</i> variant c.5603A>T in five <i>ABCA4</i> carriers. In three of them, the variant was found to be associated with known disease-causing alleles that always carry the c.5603A>T in cis. According to recent publications, the subjects could still be considered <i>ABCA4</i> carriers because both variants are on the same allele. In the remaining two subjects, c.5603A>T could be in trans with the previously known <i>ABCA4</i> variant, and the subjects were therefore excluded from the study since they could no longer be considered as carriers only. Statistical comparison of ffERG parameters showed significant reduction of the isolated rod, -as well as the combined rod-cone amplitudes over the five years of follow-up, but not compared with the controls. Concerning macular function, mfERG amplitudes were reduced for all rings in the carriers compared with the controls. Fundus photographs demonstrated morphological changes in 64% of the carriers, and 36% of them had further changes at follow-up. FAF images showed alterations in 55% of the carriers, with increased changes in 36% of them. Abnormalities on OCT were observed in 82% of the carriers, of whom 9% had newly found abnormalities at follow-up.","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/06/b2/mv-v28-300.PMC9603925.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10412964","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":"Oxidative stress alters transcript localization of disease-associated genes in the retinal pigment epithelium.","authors":"Tadeusz J Kaczynski,&nbsp;Elizabeth D Au,&nbsp;Michael H Farkas","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Nuclear retention is a mechanism whereby excess RNA transcripts are stored in the event that a cell needs to quickly respond to a stimulus; maintaining proper nuclear-to-cytoplasmic balance is important for cellular homeostasis and cell function. There are many mechanisms that are employed to determine whether to retain a transcript or export it to the cytoplasm, although the extent to which tissue or cell type, internal and external stressors, and disease pathogenesis affect this process is not yet clear. As the most biochemically active tissue in the body, the retina must mitigate endogenous and exogenous stressors to maintain cell health and tissue function. Oxidative stress, believed to contribute to the pathogenesis or progression of age-related macular degeneration (AMD) and inherited retinal dystrophies (IRDs), is produced both internally from biochemical processes as well as externally from environmental insult. Here, we evaluate the effect of oxidative stress on transcript localization in the retinal pigment epithelium (RPE), with specific focus on transcripts related to RPE function and disease.</p><p><strong>Methods: </strong>We performed poly(A) RNA sequencing on nuclear and cytoplasmic fractions from human induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells exposed to hydrogen peroxide (H₂O₂), as well as on untreated controls.</p><p><strong>Results: </strong>Under normal conditions, the number of mRNA transcripts retained in the nucleus exceeded that found in studies on other tissues. Further, the nuclear-to-cytoplasmic ratio of transcripts was altered following oxidative stress, as was the retention of genes associated with AMD and IRDs, as well as those that are important for RPE physiology.</p><p><strong>Conclusions: </strong>These results provide a localization catalog of all expressed mRNA in iPSC-RPE under normal conditions and after exposure to H₂O₂, shedding light on the extent to which H₂O₂ alters transcript localization and potentially offering insight into one mechanism through which oxidative stress may contribute to the progression of visual disorders.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/e2/fe/mv-v28-340.PMC9603899.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10404308","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":"Psychological stress induces moderate pathology in the ganglion cell layer in mice.","authors":"Dandan Zhang,&nbsp;Nannan Sun,&nbsp;Congcong Guo,&nbsp;Jun Hui Lee,&nbsp;Jiamin Zhang,&nbsp;Zhenni Zhao,&nbsp;Xiaowei Yu,&nbsp;Ying Han,&nbsp;Jian Ge,&nbsp;Zhigang Fan","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Primary open-angle glaucoma (POAG) is a condition with unclear pathogenesis. Researchers have observed an increased incidence of young Chinese POAG patients who manifest significant psychological stress while their intraocular pressure (IOP) is normal or close to normal; we hypothesize that psychological stress may play a causal role in initiating POAG.</p><p><strong>Methods: </strong>Twenty-four male C57BL/6 mice were included and divided randomly into two groups. A chronic unpredictable mild stress (CUMS) mouse model was established to evaluate the effect of psychological stress on glaucoma-related retinal pathologies. Body weight and IOP were recorded weekly. At 5 weeks after the CUMS procedure, a behavior test, serum corticosterone level, retinal nerve fiber layer (RNFL) thickness, retinal ganglion cell (RGC) number and neurotrophic factor expression were evaluated and compared between the CUMS group and the control group.</p><p><strong>Results: </strong>CUMS exposure induced depression-like behaviors, lighter body weight, and increased serum corticosterone levels in mice. RNFL thinning and neural cell loss in the ganglion cell layer (GCL) were observed in CUMS mice without significant IOP elevation. Decreased mRNA expression and protein levels of neurotropic factors in retinas of CUMS mice were observed, especially brain-derived neurotrophic factor (BDNF).</p><p><strong>Conclusions: </strong>The CUMS mouse model demonstrated that psychological stress induced glaucoma-like changes in the retinas of CUMS mice. The mechanism by which psychological stress induces retina defects may be due to a reduced expression of retinal neurotropic factors. Thus, we conclude that psychological stress is causally associated with POAG.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/7e/08/mv-v28-451.PMC9784625.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10534125","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":"Safety evaluation and pharmacodynamics of minocycline hydrochloride eye drops.","authors":"Xiaoli Li,&nbsp;Wenhua Zhang,&nbsp;Zhiqiang Ye,&nbsp;Shuaili Pei,&nbsp;Dongliang Zheng,&nbsp;Lin Zhu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluated the safe dosage of minocycline hydrochloride (Mino) eye drops and investigated the potential for the prevention or reduction of retinal damage in a diabetic rat model.</p><p><strong>Methods: </strong>Various concentrations of Mino were applied to human corneal epithelial cells (HCECs) to determine the half maximal inhibitory concentration (IC₅₀). The safety of Mino eye drops was evaluated on Sprague-Dawley (SD) rat eyes by slit-lamp examination, electroretinography (ERG), histology, and TUNEL assay. Eye drops (1 mg/ml) were applied to the streptozotocin-induced diabetic SD rats. Clinical observations, ERG analyses, and optical coherence tomography analyses were performed monthly for five months. Eyes were then analyzed via histology, blood-retinal barrier function assay, and retinal vascular staining.</p><p><strong>Results: </strong>Cytotoxicity analysis using HCECs revealed that the IC₅₀ was 250 µg/ml. Safety analyses in healthy SD rats showed that Mino eye drops did not demonstrate any ocular toxicity. Pharmacodynamics analysis showed that retinal thickness at three months was greater in the Mino group than in the non treated (NT) group. The peak times and amplitudes of each program were better in the Mino group than in the NT group at each time point by ERG analyses. Histology examinations showed a thinner ganglion cell layer, fewer ganglion cells, and more dilated blood vessels in the NT group than in the Mino group.</p><p><strong>Conclusion: </strong>Mino eye drops at 1 mg/ml were safe when used in SD rats. Mino eye drops can protect the retina from the development or progression of diabetic retinopathy.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/b6/85/mv-v28-460.PMC9784630.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10534553","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":"Analysis of hemopexin plasma levels in patients with age-related macular degeneration.","authors":"Susette Lauwen,&nbsp;Bjorn Bakker,&nbsp;Eiko K de Jong,&nbsp;Sascha Fauser,&nbsp;Carel B Hoyng,&nbsp;Dirk J Lefeber,&nbsp;Anneke I den Hollander","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>A protein quantitative trait locus (pQTL) analysis recently revealed a strong association between hemopexin (HPX) levels and genetic variants at the complement factor H (<i>CFH</i>) locus. In this study, we aimed to determine HPX plasma levels in patients with age-related macular degeneration (AMD) and to compare them with those in controls. We also investigated whether genetic variants at the <i>CFH</i> locus are associated with HPX plasma levels.</p><p><strong>Methods: </strong>HPX levels were quantified in 200 advanced AMD cases and 200 controls using an enzyme-linked immunosorbent assay and compared between the two groups. Furthermore, HPX levels were analyzed per genotype group of three HPX-associated variants (rs61818956, rs10494745, and rs10801582) and four AMD-associated variants (rs794362 [proxy for rs187328863], rs570618, rs10922109, and rs61818924 [proxy for rs61818925]) at the <i>CFH</i> locus.</p><p><strong>Results: </strong>HPX levels were similar in the control group compared with the AMD group. The three variants at the <i>CFH</i> locus, which were previously associated with the HPX levels, showed no association with the HPX levels in our data set. No significant differences in HPX levels were detected between the different genotype groups of AMD-associated variants at the <i>CFH</i> locus.</p><p><strong>Conclusions: </strong>In this study, HPX levels were not associated with AMD or AMD-associated variants at the <i>CFH</i> locus. The finding of a previous pQTL study that variants at the <i>CFH</i> locus were associated with HPX levels was also not confirmed in this study.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/fb/f6/mv-v28-536.PMC10115365.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9386632","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":"Using optical coherence tomography angiography as a biomarker of retinopathy severity and treatment for diabetic retinopathy.","authors":"Melanie Scheive,&nbsp;Kathryn L Reinhart,&nbsp;Amir R Hajrasouliha","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>The goal was to evaluate optical coherence tomography angiography (OCT-A) as a biomarker to correlate retinal vessel density (VD) with diabetic retinopathy (DR) severity and visual acuity, as well as track antivascular endothelial growth factor (VEGF) treatment efficacy.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed the automatically quantified VDs of the superficial vascular complex (SVC) and deep vascular complex (DVC), including the whole, foveal, and parafoveal VDs, on quality OCT-A scans in patients diagnosed with DR. A multivariate linear regression and analysis of variance (ANOVA) analysis compared VDs to DR severity, visual acuity, and demographic factors. A linear mixed analysis determined the effects of VD by whether anti-VEGF therapy was given to patients with OCT-A scans at multiple time points.</p><p><strong>Results: </strong>There was a positive correlation of the VDs in both the SVC whole and parafoveal VD and DVC parafoveal VD with decreased DR severity and increased visual acuity (p≤0.001). The DVC whole VD was also positively correlated with increased visual acuity (p<0.001). There was no difference in the VDs associated with anti-VEGF treatment over time.</p><p><strong>Conclusions: </strong>OCT-A VD shows promise for diagnosing and monitoring DR using DR severity and visual acuity. Anti-VEGF treatment had no significant effect (p=0.063) on vascular density in diabetic retinopathy.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/8c/98/mv-v28-220.PMC9514547.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9264396","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":"Lipoxin A4 alleviates inflammation in <i>Aspergillus fumigatus-</i>stimulated human corneal epithelial cells by Nrf2/HO-1 signaling pathway.","authors":"Xudong Peng,&nbsp;Xiaojia Zhu,&nbsp;Junjie Luan,&nbsp;Jing Lin,&nbsp;Yingxue Zhang,&nbsp;Qian Wang,&nbsp;Guiqiu Zhao","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the therapeutic effect of lipoxin A4 (LXA4) on <i>Aspergillus fumigatus (A. fumigatus)</i>-stimulated human corneal epithelial cells (HCECs).</p><p><strong>Methods: </strong>The cell counting kit-8 (CCK-8) was performed in HCECs to evaluate the toxicity of LXA4. A cell scratch test was used to assess the impact of LXA4 on the migration of HCECs. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were applied to examine the expression of inflammatory mediators in <i>A. fumigatus</i>-stimulated HCECs. The nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and expression in HCECs were detected by immunofluorescence staining.</p><p><strong>Results: </strong>LXA4 at 0-10 nmol·L^-1 (nM) had no significant cytotoxic effect on HCECs. LXA4 at a concentration of 1 nM and 10 nM significantly promoted the migration rate of HCECs. The mRNA and protein levels of pro-inflammatory mediators, including IL-1β, TNF-α, and IL-6, were remarkably lower in the LXA4-treated group. LXA4 promoted the expression of Nrf2 and heme oxygenase 1 (HO-1) in <i>A. fumigatus</i>-stimulated HCECs compared with the PBS control group. Pretreatment with brusatol (BT, Nrf2 inhibitor) or Zine Protoporphyrin (Znpp, HO-1 inhibitor) receded the anti-inflammatory ability of LXA4.</p><p><strong>Conclusions: </strong>LXA4 plays a protective role in <i>A. fumigatus</i>-stimulated HCECs by inhibiting the expression of pro-inflammatory mediators through the Nrf2/HO-1 signaling pathway.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":null,"pages":null},"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/30/86/mv-v28-441.PMC9767844.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9098305","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}