Experimental eye research最新文献_第6页

Differential possession of type 6 secretion system effector genes in exoU and exoS Pseudomonas aeruginosa in microbial keratitis 微生物性角膜炎exoU和exoS铜绿假单胞菌6型分泌系统效应基因的差异

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-16 DOI: 10.1016/j.exer.2026.110868

Tanzina Akter , Abrar Maswood Haider , Fiona Stapleton , Mark Willcox

Corneal infection (microbial keratitis; MK) is most frequently caused by Pseudomonas aeruginosa, which can utilize an array of secreted virulence factors for pathogenesis. Invasive strains of P. aeruginosa possessing the exoS gene, invade mammalian cells, while cytotoxic strains with the exoU gene rapidly kill host cells. This study investigated the presence of the type six secretion system (T6SS) effector genes in exoU and exoS strains isolated from MK. Fourteen different T6SS effector genes within 20 exoU and 19 exoS P. aeruginosa were explored using whole genome sequence data by BLAST search. To confirm the BLAST search result, PCR was used to detect exoU, exoS and those genes significantly different in the BLAST search, in a separate set of 56 MK isolates from India (24) and Australia (32). The phospholipase D (PLD) activity was measured using the Amplex Red Phospholipase D Assay kit. Three effector genes, tse7, tle1, and pldA, were differentially possessed in the exoU and exoS strains in the BLAST search (p < 0.05). When combining the BLAST search and PCR results, pldA was significantly more common in exoU (81.8%) than the exoS strains (37.3%) (p < 0.01) and trends were similar in Indian (81% exoU vs 45.5% exoS) and Australian (82.6% exoU vs 23% exoS) isolates. PldA expression was associated with detectable PLD activity. Irrespective of geographical region, pldA was more commonly found in exoU P. aeruginosa. While MK due to exoU is generally more severe than those due to exoS, the association between expression of pldA and its function requires further investigation.

角膜感染（微生物角膜炎；MK）最常见的是由铜绿假单胞菌引起的，它可以利用一系列分泌的毒力因子来致病。带有exoS基因的铜绿假单胞菌侵袭性菌株侵入哺乳动物细胞，而带有exoU基因的细胞毒菌株则能迅速杀死宿主细胞。本研究对MK分离株exoU和exoS中6型分泌系统（T6SS）效应基因的存在进行了研究，利用BLAST搜索方法，在20株exoU和19株exoS中发现了14个不同的T6SS效应基因。为了证实BLAST搜索结果，我们在来自印度（24）和澳大利亚（32）的56株MK分离株中使用PCR检测exoU、exoS和BLAST搜索中显著不同的基因。采用Amplex Red phospholipase D Assay kit测定磷脂酶D （PLD）活性。在BLAST搜索中，exoU和exoS菌株中存在三个不同的效应基因，即tse7、tle1和pldA

{"title":"Differential possession of type 6 secretion system effector genes in exoU and exoS Pseudomonas aeruginosa in microbial keratitis","authors":"Tanzina Akter , Abrar Maswood Haider , Fiona Stapleton , Mark Willcox","doi":"10.1016/j.exer.2026.110868","DOIUrl":"10.1016/j.exer.2026.110868","url":null,"abstract":"<div><div>Corneal infection (microbial keratitis; MK) is most frequently caused by <em>Pseudomonas aeruginosa,</em> which can utilize an array of secreted virulence factors for pathogenesis. Invasive strains of <em>P. aeruginosa</em> possessing the <em>exoS</em> gene, invade mammalian cells, while cytotoxic strains with the <em>exoU</em> gene rapidly kill host cells. This study investigated the presence of the type six secretion system (T6SS) effector genes in <em>exoU</em> and <em>exoS</em> strains isolated from MK. Fourteen different T6SS effector genes within 20 <em>exoU</em> and 19 <em>exoS P. aeruginosa</em> were explored using whole genome sequence data by BLAST search. To confirm the BLAST search result, PCR was used to detect <em>exoU, exoS</em> and those genes significantly different in the BLAST search, in a separate set of 56 MK isolates from India (24) and Australia (32). The phospholipase D (PLD) activity was measured using the Amplex Red Phospholipase D Assay kit. Three effector genes, <em>tse7</em>, <em>tle1</em>, and <em>pldA,</em> were differentially possessed in the <em>exoU</em> and <em>exoS</em> strains in the BLAST search (<em>p</em> < 0.05). When combining the BLAST search and PCR results, <em>pldA</em> was significantly more common in <em>exoU</em> (81.8%) than the <em>exoS</em> strains (37.3%) (<em>p</em> < 0.01) and trends were similar in Indian (81% <em>exoU</em> vs 45.5% <em>exoS</em>) and Australian (82.6% <em>exoU</em> vs 23% <em>exoS)</em> isolates. <em>PldA</em> expression was associated with detectable PLD activity. Irrespective of geographical region, <em>pldA</em> was more commonly found in <em>exoU P. aeruginosa.</em> While MK due to <em>exoU</em> is generally more severe than those due to <em>exoS</em>, the association between expression of <em>pldA</em> and its function requires further investigation.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110868"},"PeriodicalIF":2.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synaptopathy in cone and rod cells after retinal detachment and reattachment 视网膜脱离和再附着后锥体和杆状细胞的突触病变。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-16 DOI: 10.1016/j.exer.2026.110870

Ellen Townes-Anderson , Éva Halász , Ilene Sugino , Amy L. Davidow , Luke Fritzky , Fawad A.K. Yousufzai , Marco Zarbin

Using the powerful technique of stimulated emission depletion (STED) confocal microscopy in combination with 3D imaging, we describe the degeneration of cone and rod synapses after one week of retinal detachment in a porcine model. Synaptic invaginations are lost, ribbons change size and shape, and bipolar dendrites sprout. Spontaneous reattachment after hours up to 2 days after detachment appears to restore cone pedicles but does not repair rod spherules one week later. Disjunction of rod synapses remains, both at the point of initial detachment and in areas that were not detached. Moreover, electroretinographic recording of photopic and scotopic b-waves and the flicker response demonstrate that synaptic function of both cone and rod cells remains impaired, even though a-wave function has returned to baseline. The beneficial effects of subretinal injection of the Rho kinase (ROCK) inhibitor AR13503 at the time of detachment, previously shown to reduce injury 2 days after detachment, are now shown to remain for one week. Structural and functional synaptic degeneration is significantly reduced for both cone and rod photoreceptors with ROCK inhibition.

The persistence of synaptic injury after these relatively small detachments that is followed by rapid reattachment indicates the vulnerability of photoreceptor synapses to injury, in part due to increased Rho signaling. Further, the data suggest that visual dysfunction seen in patients after detachment and otherwise successful reattachment can be a result of synaptopathy. Finally, the results reinforce the potential for ROCK inhibition to reduce injury due to iatrogenic detachment in procedures such as gene therapy.

利用强大的刺激发射损耗（STED）共聚焦显微镜技术结合3D成像，我们描述了猪模型视网膜脱离一周后锥体和杆突触的变性。突触内陷消失，带状改变大小和形状，双极树突发芽。在脱离后2天内，数小时内自发再附着似乎可以恢复椎弓根，但一周后不能修复杆状小球体。杆状突触的分离仍然存在，无论是在最初的分离点还是在未分离的区域。此外，视网膜电图记录的光性和暗性b波以及闪烁反应表明，尽管a波功能已经恢复到基线，但锥细胞和杆状细胞的突触功能仍然受损。在脱离时视网膜下注射Rho激酶（ROCK）抑制剂AR13503的有益作用，先前显示在脱离后2天减少损伤，现在显示持续一周。结构和功能突触变性显著减少锥体和杆状光感受器与ROCK抑制。在这些相对较小的分离之后，突触损伤的持续存在，随后是快速的再附着，这表明光感受器突触容易受到损伤，部分原因是Rho信号的增加。此外，数据表明，在脱离或成功再附着的患者中看到的视觉功能障碍可能是突触病的结果。最后，研究结果强化了ROCK抑制在基因治疗等过程中减少医源性脱离造成的损伤的潜力。

{"title":"Synaptopathy in cone and rod cells after retinal detachment and reattachment","authors":"Ellen Townes-Anderson , Éva Halász , Ilene Sugino , Amy L. Davidow , Luke Fritzky , Fawad A.K. Yousufzai , Marco Zarbin","doi":"10.1016/j.exer.2026.110870","DOIUrl":"10.1016/j.exer.2026.110870","url":null,"abstract":"<div><div>Using the powerful technique of stimulated emission depletion (STED) confocal microscopy in combination with 3D imaging, we describe the degeneration of cone and rod synapses after one week of retinal detachment in a porcine model. Synaptic invaginations are lost, ribbons change size and shape, and bipolar dendrites sprout. Spontaneous reattachment after hours up to 2 days after detachment appears to restore cone pedicles but does not repair rod spherules one week later. Disjunction of rod synapses remains, both at the point of initial detachment and in areas that were not detached. Moreover, electroretinographic recording of photopic and scotopic b-waves and the flicker response demonstrate that synaptic function of both cone and rod cells remains impaired, even though a-wave function has returned to baseline. The beneficial effects of subretinal injection of the Rho kinase (ROCK) inhibitor AR13503 at the time of detachment, previously shown to reduce injury 2 days after detachment, are now shown to remain for one week. Structural and functional synaptic degeneration is significantly reduced for both cone and rod photoreceptors with ROCK inhibition.</div><div>The persistence of synaptic injury after these relatively small detachments that is followed by rapid reattachment indicates the vulnerability of photoreceptor synapses to injury, in part due to increased Rho signaling. Further, the data suggest that visual dysfunction seen in patients after detachment and otherwise successful reattachment can be a result of synaptopathy. Finally, the results reinforce the potential for ROCK inhibition to reduce injury due to iatrogenic detachment in procedures such as gene therapy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110870"},"PeriodicalIF":2.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in molecular genetics and multi-omics of exfoliation syndrome 脱落综合征的分子遗传学和多组学研究进展。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-16 DOI: 10.1016/j.exer.2026.110864

ZhouQi Guo, YiNu Ma, JiaXuan Zhang, XiangLong Yi

Exfoliation syndrome (XFS) is a systemic disorder of the extracellular matrix characterized by the progressive deposition of abnormal fibrillar material in the tissues of the anterior segment, and is a major cause of secondary glaucoma and irreversible vision loss worldwide. Despite the identification of multiple risk factors, the molecular pathogenesis of XFS remains incompletely understood. In addition to the well-recognized susceptibility variants in LOXL1 and CACNA1A, recent studies have identified strong associations between XFS risk and novel genetic loci, including CLU and CYP39A1. Beyond genetic influences, alterations in DNA methylation, non-coding RNA expression, protein profiles, and metabolic signatures have also been implicated in the development and progression of this disease. This review summarizes the molecular genetic mechanisms and multi-omics findings related to XFS, with the objective of establishing a theoretical foundation for the discovery of early diagnostic biomarkers and potential therapeutic targets.

脱落综合征（Exfoliation syndrome， XFS）是一种细胞外基质的全身性疾病，其特征是异常纤维物质在前段组织中进行性沉积，是世界范围内继发性青光眼和不可逆视力丧失的主要原因。尽管确定了多种危险因素，但XFS的分子发病机制仍不完全清楚。除了LOXL1和CACNA1A中公认的易感性变异外，最近的研究还发现XFS风险与新的遗传位点（包括CLU和CYP39A1）之间存在很强的关联。除遗传影响外，DNA甲基化、非编码RNA表达、蛋白质谱和代谢特征的改变也与该病的发生和进展有关。本文就XFS的分子遗传机制和多组学研究进展进行综述，旨在为发现XFS的早期诊断生物标志物和潜在治疗靶点奠定理论基础。

引用次数: 0

Rapid anterior segment and divergent corneal shape remodeling drive astigmatic compensation in the chick model 快速前段和发散性角膜形状重塑驱动鸡模型的散光代偿

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-13 DOI: 10.1016/j.exer.2026.110861

Yuanyuan Liang , Tsz Wing Leung , Patience Ansomah Ayerakwah , Byung Soo Kang , Chea-su Kee

This study investigated early temporal dynamics of ocular compensation to imposed astigmatic blur, specifically anterior segment alterations in a chick model. Fifty-four chickens were equally randomized to treatment or control groups at post-hatching day 5 (baseline, T0). Crossed-cylindrical lens (+4.00 DS/−8.00 DC) was used to induce astigmatic blur on the right eye for two weeks: With-the-rule (WTR, axis 90°) and Against-the-rule (ATR, axis 180°) astigmatism. Ocular axial dimensions and objective refraction were measured daily for the first four days (T0-T3), and at one (T7) and two weeks (T14). Corneal topography was measured at T3, T7 and T14. Our results showed that chicks treated with crossed-cylindrical lenses developed significantly higher refractive astigmatism compared to the control group (all p < 0.01), plateauing within two days. Corneal astigmatism diverged over two weeks, increasing in the WTR group but decreasing in the ATR groups, while internal astigmatism showed opposite trends. Critically, anterior segment changes emerged by T3: the ATR group exhibited a significantly deeper anterior chamber (T3: p = 0.034), and both treatment groups showed significantly thinner crystalline lenses (ATR: T2, p = 0.008; T3, p = 0.007; WTR: T3, p = 0.043) compared to controls. These changes persisted throughout the treatment. To conclude, refractive astigmatism compensated rapidly (plateauing within two days) in response to astigmatic blur, while corneal astigmatism exhibited divergent changes over two weeks. The persistent anterior segment alterations—lens thinning and anterior chamber deepening—demonstrate a key compensatory role for anterior ocular structures beyond corneal plasticity alone.

本研究调查了早期的时间动态眼代偿强加的散光模糊，特别是前段的变化，在一个小鸡模型。54只鸡在孵化后第5天（基线，T0）随机分为处理组和对照组。采用交叉柱状晶状体（+4.00 DS/−8.00 DC）诱导右眼散光模糊2周：顺行（WTR，轴90°）和反行（ATR，轴180°）散光。前4天（T0-T3）、第1周（T7）和第2周（T14）每天测量眼轴尺寸和物镜屈光度。在T3、T7、T14时测量角膜地形图。结果表明，与对照组相比，经交叉柱面透镜处理的雏鸡的屈光散光明显增加（p < 0.01），并在2天内趋于稳定。角膜散光在两周内出现分化，WTR组增加，ATR组减少，而内部散光则呈现相反的趋势。重要的是，T3出现了前段的改变：与对照组相比，ATR组的前房明显加深（T3: p = 0.034），两个治疗组的晶状体明显变薄（ATR: T2, p = 0.008; T3, p = 0.007; WTR: T3, p = 0.043）。这些变化在整个治疗过程中持续存在。综上所述，屈光散光对散光模糊的反应补偿迅速（2天内稳定），而角膜散光在两周内表现出不同的变化。持续的前段改变——晶状体变薄和前房加深——表明除了角膜可塑性外，前眼结构还具有重要的代偿作用。

{"title":"Rapid anterior segment and divergent corneal shape remodeling drive astigmatic compensation in the chick model","authors":"Yuanyuan Liang , Tsz Wing Leung , Patience Ansomah Ayerakwah , Byung Soo Kang , Chea-su Kee","doi":"10.1016/j.exer.2026.110861","DOIUrl":"10.1016/j.exer.2026.110861","url":null,"abstract":"<div><div>This study investigated early temporal dynamics of ocular compensation to imposed astigmatic blur, specifically anterior segment alterations in a chick model. Fifty-four chickens were equally randomized to treatment or control groups at post-hatching day 5 (baseline, T0). Crossed-cylindrical lens (+4.00 DS/−8.00 DC) was used to induce astigmatic blur on the right eye for two weeks: With-the-rule (WTR, axis 90°) and Against-the-rule (ATR, axis 180°) astigmatism. Ocular axial dimensions and objective refraction were measured daily for the first four days (T0-T3), and at one (T7) and two weeks (T14). Corneal topography was measured at T3, T7 and T14. Our results showed that chicks treated with crossed-cylindrical lenses developed significantly higher refractive astigmatism compared to the control group (all <em>p</em> < 0.01), plateauing within two days. Corneal astigmatism diverged over two weeks, increasing in the WTR group but decreasing in the ATR groups, while internal astigmatism showed opposite trends. Critically, anterior segment changes emerged by T3: the ATR group exhibited a significantly deeper anterior chamber (T3: <em>p</em> = 0.034), and both treatment groups showed significantly thinner crystalline lenses (ATR: T2, <em>p</em> = 0.008; T3, <em>p</em> = 0.007; WTR: T3, <em>p</em> = 0.043) compared to controls. These changes persisted throughout the treatment. To conclude, refractive astigmatism compensated rapidly (plateauing within two days) in response to astigmatic blur, while corneal astigmatism exhibited divergent changes over two weeks. The persistent anterior segment alterations—lens thinning and anterior chamber deepening—demonstrate a key compensatory role for anterior ocular structures beyond corneal plasticity alone.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110861"},"PeriodicalIF":2.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Betanin protects against diabetic retinal damage via the inhibition of NF-κB/NLRP3/VEGF axis: Insights from network pharmacology and experimental studies 甜菜素通过抑制NF-κB/NLRP3/VEGF轴保护糖尿病视网膜损伤：网络药理学和实验研究的见解

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-13 DOI: 10.1016/j.exer.2026.110863

Sawsan Zaitone , Nema Soliman , Amany M. Shalaby , Ahmed A. Abdelgbar , Mohamed A.K. Saleh , Ahmed A. Farrag , Abdelhakeem A. Elaskary , Esam Ghanem Abu El Wafa , Amira H. Eltrawy , Fatma Azzahraa Hisham , Sozan M. Abdelkhalig , Rehab M. El-Sayed

Diabetic retinopathy (DIR) is a predominant diabetic microvascular complication that may cause vision loss. Retinal inflammation and angiogenesis contribute largely to the neuronal degeneration in DIR. The current study is aiming to test the effect of oral betanin doses in protection from DIR in rats along with a network pharmacology study to investigate an assumption that betanin may inhibit nuclear factor-κ B (NF-κB). Three rat groups were assigned as vehicle, DIR, and DIR + Betanin 100 mg/kg. Molecular docking indicated the possible binding between betanin and NF-κB while the bioinformatic study highlighted a relation between this possible inhibition and suppression of NOD-like receptor pyrin domain-containing protein 3/vascular endothelial growth factor (NLRP3/VEGF) axis. The rat experimental study validated this assumption and indicated a protective effect for betanin on rat retinas as shown by routine hematoxylin and eosin staining (retinal thickness and ganglion cell count) and periodic acid-Schiff staining that was mediated through mitigating expression/protein level for of NF-κB, NLRP3, TNF-α, IL-6 and VEGF proteins. Immunohistochemistry showed that betanin was able to suppress retinal content of the glial fibrillary acidic protein (GFAP). In conclusion, the current study indicated that betanin was a good candidate for DIR in rats through suppression of the inflammatory cascade and may be suggested for diabetic patients if appropriated clinical studies will be available.

糖尿病视网膜病变（DIR）是一种主要的糖尿病微血管并发症，可导致视力丧失。视网膜炎症和血管生成在很大程度上促进了视网膜病变的神经元变性。本研究旨在检测口服甜菜素对大鼠DIR的保护作用，并通过网络药理学研究来探讨甜菜素可能抑制核因子-κB （NF-κB）的假设。3组大鼠分别作为对照、DIR和DIR +甜菜素100 mg/kg。分子对接提示甜菜素可能与NF-κB结合，生物信息学研究强调了这种可能的抑制与nod样受体pyrin结构域蛋白3/血管内皮生长因子（NLRP3/VEGF）轴的抑制之间的关系。大鼠实验研究证实了这一假设，并通过常规苏木精和伊红染色（视网膜厚度和神经节细胞计数）和周期性酸希夫染色显示了甜菜素对大鼠视网膜的保护作用，这是通过降低NF-κB、NLRP3、TNF-α、IL-6和VEGF蛋白的表达/蛋白水平介导的。免疫组织化学表明，甜菜素能够抑制视网膜胶质原纤维酸性蛋白（GFAP）的含量。总之，目前的研究表明，甜菜素通过抑制炎症级联，是大鼠DIR的良好候选者，如果有适当的临床研究，可能会建议用于糖尿病患者。

{"title":"Betanin protects against diabetic retinal damage via the inhibition of NF-κB/NLRP3/VEGF axis: Insights from network pharmacology and experimental studies","authors":"Sawsan Zaitone , Nema Soliman , Amany M. Shalaby , Ahmed A. Abdelgbar , Mohamed A.K. Saleh , Ahmed A. Farrag , Abdelhakeem A. Elaskary , Esam Ghanem Abu El Wafa , Amira H. Eltrawy , Fatma Azzahraa Hisham , Sozan M. Abdelkhalig , Rehab M. El-Sayed","doi":"10.1016/j.exer.2026.110863","DOIUrl":"10.1016/j.exer.2026.110863","url":null,"abstract":"<div><div>Diabetic retinopathy (DIR) is a predominant diabetic microvascular complication that may cause vision loss. Retinal inflammation and angiogenesis contribute largely to the neuronal degeneration in DIR. The current study is aiming to test the effect of oral betanin doses in protection from DIR in rats along with a network pharmacology study to investigate an assumption that betanin may inhibit nuclear factor-κ B (NF-κB). Three rat groups were assigned as vehicle, DIR, and DIR + Betanin 100 mg/kg. Molecular docking indicated the possible binding between betanin and NF-κB while the bioinformatic study highlighted a relation between this possible inhibition and suppression of NOD-like receptor pyrin domain-containing protein 3/vascular endothelial growth factor (NLRP3/VEGF) axis. The rat experimental study validated this assumption and indicated a protective effect for betanin on rat retinas as shown by routine hematoxylin and eosin staining (retinal thickness and ganglion cell count) and periodic acid-Schiff staining that was mediated through mitigating expression/protein level for of NF-κB, NLRP3, TNF-α, IL-6 and VEGF proteins. Immunohistochemistry showed that betanin was able to suppress retinal content of the glial fibrillary acidic protein (GFAP). In conclusion, the current study indicated that betanin was a good candidate for DIR in rats through suppression of the inflammatory cascade and may be suggested for diabetic patients if appropriated clinical studies will be available.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110863"},"PeriodicalIF":2.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ocular rigidity in eyes with experimental myopia 实验性近视眼的眼强直

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-12 DOI: 10.1016/j.exer.2026.110859

Suharsha Paidimarri, Nimesh B. Patel, Krista M. Beach, Jacinth J. Priscilla, Raman P. Sah, Manoj K. Manoharan, Rakesh Maldoddi, Lisa A. Ostrin

Purpose

To evaluate ocular rigidity in experimentally induced myopic eyes compared to contralateral control eyes in young rhesus monkeys.

Methods

Eight rhesus monkeys (Macaca mulatta) were reared with monocular form-deprivation from 24 days to 150 days of age. Refraction, axial length, and intraocular pressure (IOP) were measured biweekly. After 150 days, ocular rigidity was assessed in both eyes via anterior chamber cannulation, in which controlled changes in anterior chamber volume were used to calculate the coefficient of ocular rigidity using Friedenwald's equation. Paired t-tests were used to compare form-deprived and control eyes, and Pearson's correlations were used to examine relationships between ocular rigidity, refraction, and axial length.

Results

After 150 days, form-deprived eyes were significantly less hyperopic (+0.41 ± 3.89 D vs. +3.10 ± 3.01 D, P = 0.03) and had longer axial lengths (16.54 ± 0.81 mm vs. 15.90 ± 0.76 mm, P = 0.01) than control eyes. Mean ocular rigidity coefficients were not significantly different between form-deprived and control eyes (0.054 ± 0.008 vs. 0.050 ± 0.010 μL⁻¹ P = 0.06).

Discussion

Form-deprivation myopia in young rhesus monkeys produced significant axial elongation and myopic shifts but did not significantly alter the coefficient of ocular rigidity. Although ocular rigidity showed a decreasing trend with increasing eye size, the limited range of axial lengths may have constrained statistical power to detect a small-to-moderate difference in the ocular rigidity coefficients between treated and control eyes. This work establishes direct in vivo assessment of ocular rigidity in a primate model, laying the groundwork for future approaches to examine ocular biomechanics in myopia.

目的评价实验性近视眼与对侧对照眼的眼强直。方法选取猕猴8只，在24 ~ 150日龄进行单眼形态剥夺饲养。每两周测量一次屈光、眼轴长度和眼内压。150天后，通过前房插管评估双眼眼僵硬度，其中前房容积的控制变化利用Friedenwald方程计算眼僵硬系数。配对t检验用于比较失形眼和对照眼，Pearson相关性用于检验眼强直、屈光度和眼轴长度之间的关系。结果150 D后，失形眼的远视程度显著低于对照组（+0.41±3.89 D vs +3.10±3.01 D, P = 0.03），眼轴长度显著高于对照组（16.54±0.81 mm vs 15.90±0.76 mm, P = 0.01）。失形眼和对照眼的平均眼刚度系数无显著差异（0.054±0.008 vs. 0.050±0.010 μL−1 P = 0.06）。年幼恒河猴形体剥夺性近视产生显著的眼轴伸长和近视眼移位，但对眼强直系数无显著影响。虽然眼硬度随眼睛尺寸的增大而下降，但轴向长度的有限范围可能限制了检测治疗眼和对照眼之间眼硬度系数的小到中等差异的统计能力。本研究在灵长类动物模型中建立了眼刚性的直接体内评估，为未来研究近视的眼生物力学奠定了基础。

{"title":"Ocular rigidity in eyes with experimental myopia","authors":"Suharsha Paidimarri, Nimesh B. Patel, Krista M. Beach, Jacinth J. Priscilla, Raman P. Sah, Manoj K. Manoharan, Rakesh Maldoddi, Lisa A. Ostrin","doi":"10.1016/j.exer.2026.110859","DOIUrl":"10.1016/j.exer.2026.110859","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate ocular rigidity in experimentally induced myopic eyes compared to contralateral control eyes in young rhesus monkeys.</div></div><div><h3>Methods</h3><div>Eight rhesus monkeys (<em>Macaca mulatta</em>) were reared with monocular form-deprivation from 24 days to 150 days of age. Refraction, axial length, and intraocular pressure (IOP) were measured biweekly. After 150 days, ocular rigidity was assessed in both eyes via anterior chamber cannulation, in which controlled changes in anterior chamber volume were used to calculate the coefficient of ocular rigidity using Friedenwald's equation. Paired t-tests were used to compare form-deprived and control eyes, and Pearson's correlations were used to examine relationships between ocular rigidity, refraction, and axial length.</div></div><div><h3>Results</h3><div>After 150 days, form-deprived eyes were significantly less hyperopic (+0.41 ± 3.89 D vs. +3.10 ± 3.01 D, P = 0.03) and had longer axial lengths (16.54 ± 0.81 mm vs. 15.90 ± 0.76 mm, P = 0.01) than control eyes. Mean ocular rigidity coefficients were not significantly different between form-deprived and control eyes (0.054 ± 0.008 vs. 0.050 ± 0.010 μL<sup>−1</sup> P = 0.06).</div></div><div><h3>Discussion</h3><div>Form-deprivation myopia in young rhesus monkeys produced significant axial elongation and myopic shifts but did not significantly alter the coefficient of ocular rigidity. Although ocular rigidity showed a decreasing trend with increasing eye size, the limited range of axial lengths may have constrained statistical power to detect a small-to-moderate difference in the ocular rigidity coefficients between treated and control eyes. This work establishes direct <em>in vivo</em> assessment of ocular rigidity in a primate model, laying the groundwork for future approaches to examine ocular biomechanics in myopia.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110859"},"PeriodicalIF":2.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-neuronal cell microenvironment control retinal vascular remodeling by CST3 in the oxygen-induced retinopathy in mice 非神经元细胞微环境通过CST3调控氧致视网膜病变小鼠视网膜血管重构。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-12 DOI: 10.1016/j.exer.2026.110860

Ming-yan Du , Chao Qu , Tu-jing Zhao , Yan-hui Deng , Lin Ye , Hua-ping Tian , Run-ze Li , Zheng Li , Hao-jue Xu , Jie Li , Liang Zhou , Yi Shi , Lu-lin Huang

Retinopathy of prematurity (ROP) remains the leading cause of blindness in premature infants owing to abnormal retinal blood vessels development,but molecular mechanisms are still not fully elucidated. Oxygen-induced retinopathy (OIR) mouse is the extensively used angiogenesis model for the study of ROP pathogenesis. In this study, we investigated five cell types that composed the microenvironment of retinal vessels in OIR mice by single-cell RNA sequencing (scRNA-seq) and revealed a complex and time-dependent regulation of vascular arrest and angiogenesis in the OIR microenvironment. Importantly, we also observe that Müller glia exhibit robust expression of CST3 (cysteine protease inhibitor cystatin C) during the early phase of hypoxic adaptation, leading to capillary morphogenesis in the hyaloid, disrupting physiological vascular patterning and contributing to OIR development. Altogether, our study reveals pivotal roles of the retinal microenvironment in both normal vascularization and ROP progression, suggesting that CST3 is a potential therapeutic target for ROP.

早产儿视网膜病变（ROP）是导致早产儿失明的主要原因，主要是由于视网膜血管发育异常，但其分子机制尚未完全阐明。氧诱导视网膜病变（OIR）小鼠是目前广泛应用于ROP发病机制研究的血管生成模型。在这项研究中，我们通过单细胞RNA测序（scRNA-seq）研究了构成OIR小鼠视网膜血管微环境的五种细胞类型，揭示了OIR微环境中血管骤停和血管生成的复杂和时间依赖性调控。重要的是，我们还观察到，在低氧适应的早期阶段，m ller胶质细胞表现出CST3（半胱氨酸蛋白酶抑制剂胱抑素C）的强烈表达，导致玻璃体中的毛细血管形态发生，破坏生理血管模式并促进OIR的发展。总之，我们的研究揭示了视网膜微环境在正常血管化和ROP进展中的关键作用，表明CST3是ROP的潜在治疗靶点。

{"title":"Non-neuronal cell microenvironment control retinal vascular remodeling by CST3 in the oxygen-induced retinopathy in mice","authors":"Ming-yan Du , Chao Qu , Tu-jing Zhao , Yan-hui Deng , Lin Ye , Hua-ping Tian , Run-ze Li , Zheng Li , Hao-jue Xu , Jie Li , Liang Zhou , Yi Shi , Lu-lin Huang","doi":"10.1016/j.exer.2026.110860","DOIUrl":"10.1016/j.exer.2026.110860","url":null,"abstract":"<div><div>Retinopathy of prematurity (ROP) remains the leading cause of blindness in premature infants owing to abnormal retinal blood vessels development,but molecular mechanisms are still not fully elucidated. Oxygen-induced retinopathy (OIR) mouse is the extensively used angiogenesis model for the study of ROP pathogenesis. In this study, we investigated five cell types that composed the microenvironment of retinal vessels in OIR mice by single-cell RNA sequencing (scRNA-seq) and revealed a complex and time-dependent regulation of vascular arrest and angiogenesis in the OIR microenvironment. Importantly, we also observe that Müller glia exhibit robust expression of CST3 (cysteine protease inhibitor cystatin C) during the early phase of hypoxic adaptation, leading to capillary morphogenesis in the hyaloid, disrupting physiological vascular patterning and contributing to OIR development. Altogether, our study reveals pivotal roles of the retinal microenvironment in both normal vascularization and ROP progression, suggesting that CST3 is a potential therapeutic target for ROP.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"264 ","pages":"Article 110860"},"PeriodicalIF":2.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Calpain-1 C2L domain peptide protects retinal photoreceptor cells in rhodopsin P347L transgenic rabbits Calpain-1 C2L结构域肽对红紫质P347L转基因家兔视网膜感光细胞的保护作用

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-12 DOI: 10.1016/j.exer.2026.110862

On Kosegawa , Yusaku Chukai , Minami Shimokawara , Nanami Furukawa , Tetsuro Yamashita , Taku Ozaki

Retinitis pigmentosa (RP) leads to visual impairment by causing the death of photoreceptor cells. Mitochondrial calpain-1, an intracellular enzyme dependent on Ca²⁺ signaling, induces cell death in RP by cleaving and releasing apoptosis-inducing factors from the mitochondria. Previously, we developed Tat-μCL, a mitochondrial calpain-1 inhibitor that protects the retina from degeneration in a rat model of RP. Herein, we investigated its effect on a rabbit model of RP, which is more human-like than the rat model. We used a transgenic (Tg) rabbit harboring a P347L rhodopsin mutation and applied saline or Tat-μCL to each eye of the Tg rabbit using eye drops. Before and after 8 and 16 weeks of saline or Tat-μCL instillation, we performed electroretinography (ERG) and optical coherence tomography (OCT). After measurement in week 16, each eye was collected and histologically analyzed using hematoxylin and eosin (HE) staining and immunostaining for glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, apoptosis-inducing factor, and Tat-μCL. Tat-μCL substantially inhibited retinal thinning as determined via OCT and tended to improve the amplitude of the a- and b-waves in ERG measurement compared to saline. HE staining showed that Tat-μCL preserved the number of nuclear layers in the outer nuclear layer of the retina. Mitochondrial calpain-1 inhibition using Tat-μCL as eye drops prevented retinal degeneration in Tg rabbits, similar to our previous results from the rat model. These results validate our earlier findings that Tat-μCL preserves photoreceptor cells and delays disease progression in RP. Our findings need further validation in clinical settings.

色素性视网膜炎（RP）通过引起感光细胞的死亡而导致视力障碍。线粒体calpain-1是一种依赖于Ca2+信号的细胞内酶，通过从线粒体中切割和释放凋亡诱导因子来诱导RP中的细胞死亡。在此之前，我们开发了Tat-μCL，一种线粒体calpain-1抑制剂，可以保护视网膜免受RP大鼠模型的退化。在此，我们研究了其对兔RP模型的影响，该模型比大鼠模型更像人。我们使用含有P347L视紫红质突变基因的转基因（Tg）家兔，用滴眼液将生理盐水或Tat μ cl分别滴在Tg家兔的每只眼睛上。在生理盐水或Tat μ cl滴注8和16周前后，我们分别进行视网膜电图（ERG）和光学相干断层扫描（OCT）。第16周测量后，采集每只眼，采用苏木精和伊红（HE）染色和免疫染色对胶质纤维酸性蛋白、离子钙结合转接器分子1、凋亡诱导因子、Tat-μCL进行组织学分析。通过OCT检测，Tat μ cl显著抑制视网膜变薄，与生理盐水相比，在ERG测量中有改善a波和b波振幅的趋势。HE染色显示Tat-μCL保留了视网膜外核层的核层数。用Tat μ cl作为滴眼液抑制线粒体calpain-1可防止Tg家兔视网膜变性，与我们之前在大鼠模型中的结果相似。这些结果证实了我们早期的发现，即Tat-μCL可以保存感光细胞并延缓RP的疾病进展。我们的发现需要在临床环境中进一步验证。

{"title":"Calpain-1 C2L domain peptide protects retinal photoreceptor cells in rhodopsin P347L transgenic rabbits","authors":"On Kosegawa , Yusaku Chukai , Minami Shimokawara , Nanami Furukawa , Tetsuro Yamashita , Taku Ozaki","doi":"10.1016/j.exer.2026.110862","DOIUrl":"10.1016/j.exer.2026.110862","url":null,"abstract":"<div><div>Retinitis pigmentosa (RP) leads to visual impairment by causing the death of photoreceptor cells. Mitochondrial calpain-1, an intracellular enzyme dependent on Ca<sup>2+</sup> signaling, induces cell death in RP by cleaving and releasing apoptosis-inducing factors from the mitochondria. Previously, we developed Tat-μCL, a mitochondrial calpain-1 inhibitor that protects the retina from degeneration in a rat model of RP. Herein, we investigated its effect on a rabbit model of RP, which is more human-like than the rat model. We used a transgenic (Tg) rabbit harboring a P347L rhodopsin mutation and applied saline or Tat-μCL to each eye of the Tg rabbit using eye drops. Before and after 8 and 16 weeks of saline or Tat-μCL instillation, we performed electroretinography (ERG) and optical coherence tomography (OCT). After measurement in week 16, each eye was collected and histologically analyzed using hematoxylin and eosin (HE) staining and immunostaining for glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, apoptosis-inducing factor, and Tat-μCL. Tat-μCL substantially inhibited retinal thinning as determined via OCT and tended to improve the amplitude of the a- and b-waves in ERG measurement compared to saline. HE staining showed that Tat-μCL preserved the number of nuclear layers in the outer nuclear layer of the retina. Mitochondrial calpain-1 inhibition using Tat-μCL as eye drops prevented retinal degeneration in Tg rabbits, similar to our previous results from the rat model. These results validate our earlier findings that Tat-μCL preserves photoreceptor cells and delays disease progression in RP. Our findings need further validation in clinical settings.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110862"},"PeriodicalIF":2.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic efficacy of nitazoxanide on Acanthamoeba keratitis in an experimental model nitazoxanide治疗棘阿米巴角膜炎的实验模型。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-10 DOI: 10.1016/j.exer.2026.110858

Toqa Yasser Shakour , Ahmad A. Othman , Iman A. Fahmy , Ahmed Yousef Amin Ali , Asmaa M. Eid , Eman S. El-Wakil , Hager S. Zoghroban

Acanthamoeba keratitis (AK) is a serious sight-threatening infection caused by various species of the opportunistic protozoan Acanthamoeba, especially in contact lens wearers and immunocompromised people. The aim of the study was to assess the therapeutic efficacy of two topical nitazoxanide (NTZ) formulations in experimentally induced AK. Three groups of male New Zealand white rabbits were used: group (A): infected and received NTZ in suspension form; group (B): infected and received NTZ in liquid crystal forming system; and group (C): infected and received topical chlorhexidine 0.02 %. The right eyes of the animals served as their corresponding infected untreated control. The animals were infected by Acanthamoeba isolated from human cases of AK. The effects of treatment were assessed over 30 days through daily clinical evaluation; grading of AK; and parasitological and histopathological examination of corneal tissues. The present work revealed that after inducing keratitis, signs of infection appeared on day 3, and all groups showed similar infection rates before treatment began. Corneal opacity improved significantly in animals treated by NTZ liquid crystal form, especially by days 18–30 post-treatment, scoring therapeutic outcomes comparable or superior to the chlorhexidine-treated group and markedly better than the NTZ suspension-treated group. Histopathological assessment confirmed these findings, with the NTZ liquid crystal group exhibiting minimal inflammation and no detectable cysts, highlighting its potential as an effective alternative agent against Acanthamoeba. In conclusion, NTZ in its liquid crystal form showed promise as a potential therapy for AK. Further studies are needed to establish safety and efficacy of topical NTZ in humans and its possible use in combination with other amoebicidal agents.

棘阿米巴角膜炎（AK）是一种由棘阿米巴原虫引起的严重感染，特别是在隐形眼镜佩戴者和免疫功能低下的人群中。目的是评价两种硝唑尼特（NTZ）制剂治疗实验性AK的疗效。将雄性新西兰大白兔31只分为7组：A-s组感染后给予NTZ悬浮液；组（A-c）：前一组的对照组；B-s组：感染并给药NTZ液晶形成系统；B-c组：前两组的对照组；C-s组：感染后外用0.02%氯己定；组（C-c）：前一组的对照组；组(D)：正常对照组。通过日常临床评价、AK评分、角膜组织寄生虫学和组织病理学检查，在30天内评估治疗效果。本研究发现，在诱导角膜炎后，在第3天出现感染迹象，并且所有组在治疗开始前的感染率相似。NTZ液晶形态处理组角膜混浊明显改善，特别是在第18 ~ 30天，其结果与氯己定处理组相当或优于，明显优于NTZ混悬液处理组。组织病理学分析证实了这些发现，NTZ液晶组表现出最小的炎症和未检测到的囊肿，突出了其作为AK有效替代治疗的潜力。

{"title":"Therapeutic efficacy of nitazoxanide on Acanthamoeba keratitis in an experimental model","authors":"Toqa Yasser Shakour , Ahmad A. Othman , Iman A. Fahmy , Ahmed Yousef Amin Ali , Asmaa M. Eid , Eman S. El-Wakil , Hager S. Zoghroban","doi":"10.1016/j.exer.2026.110858","DOIUrl":"10.1016/j.exer.2026.110858","url":null,"abstract":"<div><div><em>Acanthamoeba</em> keratitis (AK) is a serious sight-threatening infection caused by various species of the opportunistic protozoan <em>Acanthamoeba</em>, especially in contact lens wearers and immunocompromised people. The aim of the study was to assess the therapeutic efficacy of two topical nitazoxanide (NTZ) formulations in experimentally induced AK. Three groups of male New Zealand white rabbits were used: group (A): infected and received NTZ in suspension form; group (B): infected and received NTZ in liquid crystal forming system; and group (C): infected and received topical chlorhexidine 0.02 %. The right eyes of the animals served as their corresponding infected untreated control. The animals were infected by <em>Acanthamoeba</em> isolated from human cases of AK. The effects of treatment were assessed over 30 days through daily clinical evaluation; grading of AK; and parasitological and histopathological examination of corneal tissues. The present work revealed that after inducing keratitis, signs of infection appeared on day 3, and all groups showed similar infection rates before treatment began. Corneal opacity improved significantly in animals treated by NTZ liquid crystal form, especially by days 18–30 post-treatment, scoring therapeutic outcomes comparable or superior to the chlorhexidine-treated group and markedly better than the NTZ suspension-treated group. Histopathological assessment confirmed these findings, with the NTZ liquid crystal group exhibiting minimal inflammation and no detectable cysts, highlighting its potential as an effective alternative agent against <em>Acanthamoeba</em>. In conclusion, NTZ in its liquid crystal form showed promise as a potential therapy for AK. Further studies are needed to establish safety and efficacy of topical NTZ in humans and its possible use in combination with other amoebicidal agents.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"265 ","pages":"Article 110858"},"PeriodicalIF":2.7,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comment on “Precise biometric measurement of the mouse eye using optical coherence tomography based on optic-nerve-head imaging” 评论“基于视神经头成像的光学相干断层扫描对小鼠眼睛的精确生物测量”。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-08 DOI: 10.1016/j.exer.2026.110856

Zhili Cui , Jun Kang

引用次数: 0