Investigative ophthalmology & visual science最新文献

{"title":"Aurora A Kinase Inhibition Is Synthetic Lethal With the Activation of MYCN in Retinoblastoma.","authors":"Qili Liao, Jie Yang, Hanhan Shi, Reyizha Mengjiang, Yongyun Li, Qianqian Zhang, Xuyang Wen, Shengfang Ge, Peiwei Chai, Xianqun Fan, Renbing Jia, Jiayan Fan","doi":"10.1167/iovs.66.2.20","DOIUrl":"10.1167/iovs.66.2.20","url":null,"abstract":"<p><strong>Purpose: </strong>RB1 inactivation and MYCN activation have been documented as common oncogenic alterations in retinoblastoma (RB). Direct targeting of RB1 and MYCN has not yet been proven to be feasible. The current treatment options for RB mainly consist of conventional chemotherapy, which inevitably poses health-threatening side effects. Here, we aimed to screen an in-house compound library to identify potential drugs for the treatment of human RB.</p><p><strong>Methods: </strong>Aurora A kinase (AURKA) inhibitors were identified by differential viability screening with a tool compound library, and the pharmacological safety and efficacy of candidate drugs were further validated in zebrafish and RB patient-derived xenograft (PDX) models in vivo. Further CUT & Tag assay, ChIP-qPCR and RNA seq performances showed that MYCN binds to the AURKA promoter and upregulates its transcription, suggesting that AURKA inhibition induces synthetic lethality in RB.</p><p><strong>Results: </strong>In this study, we revealed that AURKA inhibitors exhibited high therapeutic efficacy against RB both in vitro and in vivo. Mechanistically, we found that MYCN could bind to the AURKA promoter region to regulate its transcription, thereby promoting AURKA expression and consequently driving RB progression. Interestingly, AURKA inhibition exhibited synthetic lethality with RB1-deficient and MYCN-amplification in RB cells.</p><p><strong>Conclusions: </strong>Collectively, these findings demonstrate that AURKA is crucial for RB progression and further expanded the current understanding of synthetic lethal therapeutic strategies. Our study indicates that AURKA inhibitors may represent a new therapeutic strategy for selectively targeting patients with RB with RB1-deficient and MYCN-amplification to improve the prognosis of aggressive types of patients with RB.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"20"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Responses to Short- and Longer-Term Predominant ON or OFF Stimulation in Emmetropes and Myopes.","authors":"Sandra Wagner, Annemarie Settele, Torsten Strasser","doi":"10.1167/iovs.66.2.66","DOIUrl":"10.1167/iovs.66.2.66","url":null,"abstract":"<p><strong>Purpose: </strong>The link between nearwork and myopia is controversially discussed. Features of the viewing target may stimulate eye growth, for example, black-on-white text was found to stimulate retinal OFF pathways and promote choroidal thinning, whereas inverted text led to ON pathway stimulation and thicker choroids. We used electroretinograms (ERGs) to compare retinal activity for both stimuli in the parafovea in emmetropes and myopes and studied the effects of adaptation.</p><p><strong>Methods: </strong>ERGs were recorded in 42 subjects (18-30 years) during 200 ms-flashes on a CRT monitor, superimposed with an annulus or circles filled with gray or inverted or standard text. Ganzfeld ERGs (500 ms) were taken before and after 30 minutes of reading standard or inverted text at 25 cm to determine adaptation effects. The ON- (b-wave) and OFF-responses (d-wave) were analyzed using linear mixed effects models and pointwise t-testing.</p><p><strong>Results: </strong>(1) Stimulus size affected retinal ON-responses of both groups (p < 0.001), with larger responses to a 6 to 12 degrees annulus than to a 12-degree circle. (2) Myopes displayed larger ON-responses to inverted text contrast than emmetropes within 6 to 12 degrees. (3) After adaptation to text, ON-responses were reduced (p = 0.010) irrespective of refraction and contrast. (4) Emmetropes showed reduced ON- and OFF-responses to inverted text contrast. (5) Only emmetropes had reduced ON- and larger OFF-responses after adapting to standard text.</p><p><strong>Conclusions: </strong>Myopes had largest ON-responses with inverted contrast in the perifovea. Emmetropes displayed larger adaptive changes after ON/OFF stimulation. In both groups, inverted contrast still reduced ON-responses, suggesting that efficient activation of retinal ON channels to inhibit myopia might require additional OFF channel suppression.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"66"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Signature of Serum Modified Nucleosides in Uveitis.","authors":"Haoze Zhou, Yiqiu Hu, Guangming Qin, Jinfeng Kong, Xiujuan Hong, Cheng Guo, Jian Zou, Lei Feng","doi":"10.1167/iovs.66.2.68","DOIUrl":"10.1167/iovs.66.2.68","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to evaluate the metabolism of serum-modified nucleosides in uveitis by using liquid chromatography-tandem mass spectrometry (LC-MS) and to develop potential diagnostic biomarkers for uveitis.</p><p><strong>Methods: </strong>Forty-two patients with different subtypes of uveitis (idiopathic uveitis, Vogt-Koyanagi-Harada [VKH] disease, and ankylosing spondylitis [AS]) and 32 healthy controls were recruited in this retrospective case-control study. The concentrations of 23 modified nucleosides in patient serum were quantified by LC-MS. The data was statistically analyzed with SPSS and GraphPad Prism.</p><p><strong>Results: </strong>The data revealed that 13 out of 23 modified nucleosides (m6A, m1A, m6Am, Cm, ac4C, Gm, m1G, m2G, m2,2G, Um, m3U, m5U, and m5Um) effectively showed quantifiable chromatographic peaks. The statistical results indicated that there were extremely significant differences for m2G, Gm, Cm, and m1G between healthy controls and uveitis patients. The differences for Gm, m6A,and m5U were able to further assort idiopathic uveitis and uveitis with systemic inflammation including VKH and AS. Interestingly, each specific subtype of uveitis is characterized by its signature combination of serum-modified nucleotides comparing with healthy controls.</p><p><strong>Conclusions: </strong>This study revealed that the metabolism of serum-modified nucleosides in uveitis patients display significant differences from healthy controls. The signature combination of serum modified nucleotides for each subtype of uveitis may be applied for the potential diagnosis of uveitis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"68"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrastructural Aspects of Corneal Functional Recovery in Rats Following Intrastromal Keratocyte Injection.","authors":"Qian Ma, Andri K Riau, Robert D Young, James S Bell, Olga Shebanova, Nicholas J Terrill, Gary H F Yam, Evelina Han, Keith M Meek, Jodhbir S Mehta, Craig Boote","doi":"10.1167/iovs.66.2.45","DOIUrl":"10.1167/iovs.66.2.45","url":null,"abstract":"<p><strong>Purpose: </strong>Donor tissue shortfalls and postsurgical complications are driving novel corneal tissue regeneration approaches. Corneal stromal keratocytes (CSKs) have shown promise in promoting corneal repair and restoring transparency. We investigated the impact of intrastromal CSK injection on corneal ultrastructure and proteoglycan (PG) distribution in a rat injury model.</p><p><strong>Methods: </strong>Rats were divided into four groups: normal (n = 12), injured (irregular phototherapeutic keratectomy centrally; n = 6), CSK (injured + human CSK intrastromal injection; n = 6), and PBS (injured + PBS injection; n = 6). Three weeks after treatment, corneas were examined by slit-lamp and optical coherence tomography. Corneal ultrastructure was analysed via small-angle x-ray scattering (collagen fibril diameter, interfibrillar spacing and matrix order), transmission electron microscopy with cuprolinic blue before and after chondroitinase digestion (CS/DS and KS PGs), and immunofluorescence staining (lumican and decorin).</p><p><strong>Results: </strong>Irregular phototherapeutic keratectomy caused corneal opacity and significantly disrupted stromal ultrastructure, characterized by increased haze density (P < 0.0001), change in central corneal thickness (P = 0.0005), and interfibrillar spacing (P < 0.0001), along with decreased fibril diameter (P < 0.0001), matrix order (P < 0.0001), CS/DS (P < 0.0001) and KS (P < 0.0001) PGs, lumican, and decorin. CSK injection recovered corneal clarity and native stromal ultrastructure, with haze density (P = 0.8086), change in central corneal thickness (P = 0.9503), fibril diameter (P = 0.1139), interfibrillar spacing (P = 0.5879), matrix order (P = 0.9999), CS/DS (P = 0.9969) and KS (P = 0.2877) PGs, lumican, and decorin returning to normal. In contrast, the PBS group exhibited similar corneal injury responses to the injured group.</p><p><strong>Conclusions: </strong>CSK injection resolved early stage corneal scarring by restoring stromal collagen arrangement and PG distribution, further endorsing its potential for treating corneal opacities.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"45"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11838119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depth and Strain-Dependent Structural Responses of Mouse Lens Fiber Cells During Whole Lens Shape Changes.","authors":"Sepideh Cheheltani, Mahbubul H Shihan, Justin Parreno, Sondip K Biswas, Woo-Kuen Lo, Velia M Fowler","doi":"10.1167/iovs.66.2.53","DOIUrl":"10.1167/iovs.66.2.53","url":null,"abstract":"<p><strong>Purpose: </strong>To study the relationship between whole lens shape changes and fiber cell responses to externally applied loads.</p><p><strong>Methods: </strong>Freshly dissected mouse lenses were compressed by applying glass coverslips to the lens anterior, followed by fixation to preserve lens shape, and preparation for scanning electron microscopy (SEM). SEM images were collected from the outer cortex to the nucleus, and fiber cell end-to-end curvature and membrane paddle dimensions were measured using ImageJ.</p><p><strong>Results: </strong>At 23% and 29% axial strain, cortical fiber bundle curvature increased significantly compared to control uncompressed lenses, whereas nuclear fiber bundle curvature was unaffected. Outer cortical fiber cell membrane paddles and protrusions were dramatically distorted in a radial direction, with loss of paddle-associated small protrusions in compressed lenses compared to controls, but nuclear fiber cell morphologies were unchanged. The compression-induced increases in cortical fiber cell curvature and distortion of membrane paddles were reversible, with fiber cell morphologies returning to those of control lenses after the release of load.</p><p><strong>Conclusions: </strong>Whole lens shape changes due to an increase in axial strain result in increased fiber cell curvature and distorted membrane morphologies in cortical but not nuclear fiber cells, indicating that mechanical strain dissipates with depth. The recovery of normal cortical fiber cell curvature and membrane morphologies after the removal of load and lens rounding back to its original shape suggests elastic properties of the young and mature fiber cells and their membrane paddles.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"53"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oridonin Preserves Retinal Pigmented Epithelial Cell Tight Junctions and Ameliorates Choroidal Neovascularization.","authors":"Juming Zhu, Dongmei Ding, Tao Sun, Yuting Zhang, Huizi Miao, Yunjie Gu, Ming Dai, Manhui Zhu","doi":"10.1167/iovs.66.2.56","DOIUrl":"10.1167/iovs.66.2.56","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the role and mechanism of oridonin (ORI), a bioactive diterpenoid extracted from the Chinese herbal medicine Rabdosia rubescens, on the integrity of outer blood-retinal barrier (oBRB) during choroidal neovascularization (CNV).</p><p><strong>Methods: </strong>ARPE-19 cells were exposed to hypoxia and treated with ORI. The expression of ZO-1 and occludin in the axis of TGFβR/SUV39H1/KLF11 was detected by WB, chromatin immunoprecipitation, luciferin report activity assay, and immunofluorescence assay (IF), and the effect of ORI on the barrier properties of ARPE-19 cells was studied. A laser-induced mouse CNV model was constructed, and ORI was administrated by oral gavage. IF on mouse choroid flat mounts was done to confirm the effect of ORI on BRB integrity. Indocyanine green angiography and IF on mouse retina-RPE-choroid flat mounts were performed to determine the effect of ORI on CNV formation and retinal function. Hematoxylin and eosin staining and TUNEL staining were carried out to appraise ocular and systemic cytotoxicity caused by ORI.</p><p><strong>Results: </strong>ORI protected ARPE-19 cells from hypoxia-induced destruction of barrier properties and promoted the expression of ZO-1 and occludin by the TGFβR/SUV39H1/KLF11 axis, maintaining barrier properties of ARPE-19 cells with hypoxia. ORI improved BRB integrity during laser-induced CNV in mice and mitigated laser-induced CNV formation in mice without any ocular or systemic cytotoxicity (n = 4-5 in each group).</p><p><strong>Conclusions: </strong>ORI ameliorates BRB integrity and subsequent formation of CNV via regulating the TGFβR/SUV39H1/KLF11 pathway in RPE cells.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"56"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11855140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization, Enrichment, and Computational Modeling of Cross-Linked Actin Networks in Transformed Trabecular Meshwork Cells.","authors":"Haiyan Li, Devon H Harvey, Jiannong Dai, Steven P Swingle, Anthony M Compton, Chenna Kesavulu Sugali, Kamesh Dhamodaran, Jing Yao, Tsai-Yu Lin, Todd Sulchek, Taeyoon Kim, C Ross Ethier, Weiming Mao","doi":"10.1167/iovs.66.2.65","DOIUrl":"10.1167/iovs.66.2.65","url":null,"abstract":"<p><strong>Purpose: </strong>Cross-linked actin networks (CLANs) are prevalent in the glaucomatous trabecular meshwork (TM). We previously developed the GTM3L cell line, which spontaneously forms fluorescently labeled CLANs, by transducing GTM3, a transformed glaucomatous TM cell line, with a lentivirus expressing the LifeAct-GFP fusion protein. Here, we determined if LifeAct-GFP viral copy numbers are associated with CLANs, developed approaches to increase CLAN incidence, and computationally studied the biomechanical properties of CLAN-containing GTM3L cells.</p><p><strong>Methods: </strong>GTM3L cells were fluorescently sorted for viral copy number analysis to determine whether increased CLAN incidence was associated with copy number. CLAN incidence was increased by combining (1) differential adhesion sorting, (2) cell deswelling, and (3) cell stiffness selection. GTM3L cells were cultured on glass or soft hydrogels for stiffness measurement by atomic force microscopy. Computational models studied the biomechanical properties of CLANs.</p><p><strong>Results: </strong>GTM3L cells had one LifeAct-GFP viral copy/cell on average, and viral copy number or LifeAct-GFP expression level did not associate with CLAN incidence rate. However, CLAN rate was increased from -0.28% to -50% by combining the three enrichment methods noted above. Further, GTM3L cells formed more CLANs on a stiff versus a soft substrate. Computational modeling predicted that CLANs contribute to higher cell stiffness, including increased resistance of the nucleus to tensile stress when CLANs are physically linked to the nucleus.</p><p><strong>Conclusions: </strong>It is possible to greatly enhance CLAN incidence in GTM3L cells. CLANs are mechanosensitive structures that affect cell biomechanical properties. Further research is needed to determine the biomechanics, mechanobiology, and etiology of CLANs in the TM.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"65"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthropometric Measures and Fuchs' Endothelial Corneal Dystrophy: The Women's Health Initiative Observational Study.","authors":"Yihua Yue, Sangita P Patel, Jing Nie, Chris A Andrews, Jean Wactawski-Wende, Aladdin H Shadyab, Robert Wallace, Amy E Millen","doi":"10.1167/iovs.66.2.26","DOIUrl":"10.1167/iovs.66.2.26","url":null,"abstract":"<p><strong>Purpose: </strong>Both genetic and environmental factors contribute to the development of Fuchs' endothelial corneal dystrophy (FECD), the most common indication for corneal transplantation in the United States. Prior studies have suggested an association of height, weight, or body mass index (BMI) with FECD. We examined the association between anthropometric measures and incident FECD in the Women's Health Initiative Observational Study (WHI-OS) of postmenopausal women (n = 22,983).</p><p><strong>Methods: </strong>Medicare Part B claims data from the WHI-OS baseline visit (1993-1998) to 2019 were used to identify incident cases of FECD. At baseline and follow-up year 3, weight, height, waist circumference (WC), and hip circumference were measured. At baseline, women were asked to recall their historic weight at ages 18, 35, and 50 years. At follow-up years 1 and 4 to 8, the women were asked to self-report their weight. Height and weight were used to calculate BMI at each time point. Adjusted hazard ratios (HRs), 95% confidence intervals (CI), and p for trend for incident FECD were estimated by measures of historic BMI, baseline anthropometrics measures, and anthropometric measures that incorporated more than one baseline visit (time-varying). Anthropometric measures were parameterized as continuous and categorical in analyses.</p><p><strong>Results: </strong>There were 1399 incident FECD cases with an annualized incidence rate of 5.06 per 1000 person-years (95% CI = 4.80-5.33) over 276,443 person-years of follow-up. No statistically significant associations were observed between baseline height and risk of FECD. Women with baseline BMIs ≥35 (obesity II) compared to <25 kg/m2 (normal weight or underweight) had lower risk of incident FECD (HR = 0.68, 95% CI = 0.53-0.88) with a P value = 0.0373 for an ordinal trend analysis across BMI categories. Significant inverse associations were observed for continuous measures of WC (HR = 0.97, 95% CI = 0.95-0.99 per 5 cm increase) and waist-to-hip ratio (WHR; HR = 0.92, 95% CI = 0.86-0.99 per 0.1 unit increase). No statistically significant associations were observed for time-varying BMI, but time-varying WC and WHR has statistically significant inverse associations with risk for FECD (data not shown).</p><p><strong>Conclusions: </strong>In this cohort of postmenopausal women, BMI, WC, and WHR were inversely associated with incident FECD. These findings generally support the potential role of anthropometric measures, particularly those indicative of abdominal obesity in FECD susceptibility in women.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"26"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in Optical Coherence Tomography Angiography Precede Clinical Onset of Placental Insufficiency.","authors":"Ye He, Pearl Heumann, Melissa Weilin Song, Shin Kadomoto, Srinivas R Sadda, Ilina D Pluym, Irena Tsui","doi":"10.1167/iovs.66.2.36","DOIUrl":"10.1167/iovs.66.2.36","url":null,"abstract":"<p><strong>Purpose: </strong>This prospective cohort study examined the use of optical coherence tomography angiography (OCTA) to detect in vivo retinal and choroidal variations associated with placental insufficiency, manifesting as fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP).</p><p><strong>Methods: </strong>Pregnant women were imaged with OCTA from gestational week 16 and every 4 weeks until week 36. Pregnancy outcomes were categorized into three groups: uncomplicated, complicated by late FGR, or complicated by HDP after 32 weeks. OCTA metrics, including retinal perfusion density (PD), vessel length density (VLD), and choriocapillaris flow deficits (CCFDs), were compared between groups.</p><p><strong>Results: </strong>In uncomplicated pregnancies, OCTA metrics remained stable throughout gestation. In contrast, the FGR group exhibited significant overall increases in superficial VLD (P = 0.016), decreases in deep VLD (P = 0.029), and increases in CCFDs (P = 0.002) throughout pregnancy when compared to the uncomplicated group. The HDP group showed significant overall decreases in both PD (P < 0.001) and VLD (P = 0.019) in the deep layer when compared to the uncomplicated group. Furthermore, CCFDs demonstrated strong potential for early prediction of FGR as early as week 16 (area under the curve = 0.73; P = 0.012).</p><p><strong>Conclusions: </strong>Our pilot study highlights the potential of OCTA to identify retinal and choroidal variations as biomarkers for pregnancy complications, particularly increased CCFDs in FGR.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"36"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote Preconditioning Provides Protection Against Retinal Cell Death From Retinal Detachment.","authors":"Bruna Miglioranza Scavuzzi, Sumathi Shanmugam, Mengling Yang, Jingyu Yao, Heather Hager, Bhavneet Kaur, Lin Jia, Steven F Abcouwer, David N Zacks","doi":"10.1167/iovs.66.2.34","DOIUrl":"10.1167/iovs.66.2.34","url":null,"abstract":"<p><strong>Purpose: </strong>Remote preconditioning involves injury to a tissue that results in protection to a subsequent injury in a distal tissue. Here, we investigated the impact of remote preconditioning on retinal detachment (RD) injury, hypothesizing that a previous contralateral RD would protect the fellow retina against inflammation and cell death following its detachment.</p><p><strong>Methods: </strong>RD was created in adult C57BL/6J mice with subretinal sodium hyaluronate injection. Preconditioning involved RD in the right eye at 1, 3, 7, or 28 days before left eye detachment, whereas the control group only received RD to the left eye. Retinas were harvested 24 hours post-left eye detachment in both groups. Cell death was assessed using Cell Death Detection ELISA and mRNA expression was evaluated via qRT-PCR.</p><p><strong>Results: </strong>Contralateral RD promoted a transient protection against retinal cell death from 1 to 3 days and waned by 7 days compared with control RD retinas with intact fellow retinas. Contralateral RD significantly protected against post-RD cell death (P = 0.0002) and caspase 3 cleavage (P = 0.0449), compared with control RD retinas with intact fellow retinas 1-day post-RD. Detached fellow retinas from the preconditioning group expressed significantly less Tnfa (P = 0.0066), Cxcl10 (P = 0.0099), and Fas (P = 0.0223) mRNAs, compared with the detached retinas of the control group. In contrast, upregulation of type-I-IFN pathway genes, including Irf7 (P = 0.0106) and Ifit1 (P = 0.0740), following RD was higher in the preconditioning group.</p><p><strong>Conclusions: </strong>RD in one eye produces a transient remote preconditioning effect that protects the fellow retina against retinal cell death following subsequent RD.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"34"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}