Experimental eye research最新文献_第3页

Effect of corneal cross-linking on biomechanical properties of swollen rabbit corneas 角膜交联对兔角膜肿胀生物力学性能的影响。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110191

LingQiao Li , Han Bao , ErChi Zhang , ShuTing Wu , XiaoYang Jiang , YuJia Xiao , ShiJing Fan , YiXin Luo , YunYun Huang , Pei Zhang , Michael Swain , Ahmed Elsheikh , ShiHao Chen , XiaoBo Zheng

Corneal cross-linking (CXL) is an effective method to prevent the progression of keratoconus. CXL combined with hypotonic riboflavin solution is a modified treatment for thin corneas, which are deemed to be below the safe thickness threshold. In this study, rabbit corneas were subjected to different hydration levels using different osmolarity of riboflavin dextran solutions before CXL. Inflation testing was performed to evaluate the corneal biomechanical stiffening effect of hypotonic riboflavin solutions crosslinking. One-month post-CXL, the stromal demarcation line depth (DLD) and the biomechanical property parameter – tangent modulus (Et) – were measured. All CXL groups showed higher Et than the corresponding Ctrl groups (all P < 0.001), however, the Et values showed no statistical differences between the CXL-ed groups with different hydration levels (all P > 0.05). The relative depth ratio of DLD to total corneal thickness (TCT) did not show significant differences (P > 0.05), while the DLD was statistically different in three CXL groups (P < 0.001). The research suggested that riboflavin solutions with different osmolarities are suitable for preoperative swelling of corneas with different thickness ranges. Furthermore, crosslinking with hypotonic riboflavin solutions has no significant effect on corneal biomechanical improvement under a certain degree of hydration.

角膜交联（CXL）是预防圆锥角膜发展的有效方法。CXL联合低渗核黄素溶液是一种针对薄角膜的改良治疗方法，薄角膜被认为低于安全厚度阈值。在本研究中，使用不同渗透压的核黄素葡聚糖溶液对兔角膜进行了不同水化水平的治疗。采用充气试验评价低渗核黄素交联后角膜生物力学硬化效果。术后1个月，测量基质分界线深度（DLD）和生物力学性能参数切模量（Et）。所有CXL组的Et值均高于相应的对照组（P < 0.001），但不同水合水平CXL-ed组之间Et值无统计学差异（P < 0.05）。DLD与角膜总厚度（TCT）的相对深度比差异无统计学意义（P < 0.05），而3个CXL组的DLD差异有统计学意义（P < 0.001）。研究提示，不同渗透压的核黄素溶液适用于不同厚度范围角膜的术前肿胀。在一定水化程度下，低渗核黄素交联对角膜生物力学改善无显著影响。

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引用次数: 0

Heat stress regulates the migration and proliferation of lens epithelial cells through ferroptosis and NCOA4-FTH1 interaction 热应激通过铁突变和 NCOA4-FTH1 相互作用调控晶状体上皮细胞的迁移和增殖

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110182

Lei Lin , Lili Liang , Liming Xu , Yu Zheng , Hanwen Guo , Bei Zhang , Yun-e Zhao

Posterior capsule opacification (PCO) due to the proliferation and migration of lens epithelial cells (LECs) is the main complication after surgery. Heat stress has demonstrated impressive results in halting cell proliferation and migration, while also facilitating cell death. This study aimed to investigate the role and mechanism of ferroptosis in the proliferation and migration of LECs under heat stress. CCK-8 assays, scratch assays, and transcriptome analysis were used to evaluate the impact of temperature on human lens epithelial cells (HLECs) and explore the potential mechanisms. The role of ferroptosis in the proliferation of HLECs induced by heat was investigated using the ferroptosis inhibitor Fer-1 and siRNA-mediated NCOA4 protein interference. Fluorescence staining and Western blot experiments were used to detect the expression of Fe²⁺, reactive oxygen species (ROS), and ferroptosis-related proteins NCOA4, FTH1, and SLC3A2. The results of CCK-8 assays, scratch assays, and transcriptome analysis demonstrated significant thermal effects on HLEC behavior. After heat treatment, there were significant changes in the fluorescence expression of Fe²⁺ and ROS in the HLECs and lens explant. In addition, the expression of NCOA4, FTH1, and SLC3A2 also changed significantly. Using Fer-1 or NCOA4 siRNA-mediated interference restored cell viability decreased by thermal stress. Furthermore, interference with NCOA4 protein effectively restored the expression of Fe²⁺, ROS, and FTH1. In conclusion, heat stress has a significant effect on LECs by regulating ferroptosis and the interaction between NCOA4 and FTH1 proteins play an important role.

晶状体上皮细胞（LEC）的增殖和迁移导致的后囊不透明（PCO）是手术后的主要并发症。热应激在阻止细胞增殖和迁移方面取得了令人瞩目的成果，同时也促进了细胞的死亡。本研究旨在探讨热应激下铁蛋白沉积在晶状体上皮细胞增殖和迁移中的作用和机制。研究采用 CCK-8 试验、划痕试验和转录组分析来评估温度对人类晶状体上皮细胞（HLECs）的影响，并探索其潜在机制。研究人员使用铁突变抑制剂Fer-1和siRNA介导的NCOA4蛋白干扰研究了铁突变在热诱导的HLECs增殖中的作用。荧光染色和 Western 印迹实验用于检测 Fe2+、活性氧（ROS）和铁突变相关蛋白 NCOA4、FTH1 和 SLC3A2 的表达。CCK-8 检测、划痕检测和转录组分析的结果表明，热对 HLEC 的行为有显著影响。热处理后，HLECs 和晶状体外植体中 Fe2+ 和 ROS 的荧光表达发生了显著变化。此外，NCOA4、FTH1 和 SLC3A2 的表达也发生了显著变化。使用 Fer-1 或 NCOA4 siRNA 介导的干扰可恢复因热应激而降低的细胞活力。此外，干扰 NCOA4 蛋白可有效恢复 Fe2+、ROS 和 FTH1 的表达。总之，热应激通过调节铁突变对LECs有显著影响，而NCOA4和FTH1蛋白之间的相互作用发挥了重要作用。

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引用次数: 0

A deep dive into radiation keratopathy; Going beyond the current frontierss 深入探讨放射性角膜病变；超越当前的边界。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2025.110234

Mohammad Soleimani , Seyed Mahbod Baharnoori , Hamed Massoumi , Kasra Cheraqpour , Hassan Asadigandomani , Arash Mirzaei , Mohammad Javad Ashraf , Raghuram Koganti , Madhurima Chaudhuri , Mahmood Ghassemi , Elmira Jalilian , Ali R. Djalilian

Radiotherapy is one of the conventional treatments for head and neck malignancies. Despite the implementation of protective measures to minimize the detrimental impact on healthy tissues surrounding the radiation site, radiation keratopathy remains a prevalent complication. We aimed to establish a mouse model of radiation keratopathy to characterize the pathophysiology of the disease and enable future identification of potential treatments. Thirty-six mice were divided equally into six groups. One eye of each mouse was irradiated with 5, 10, 15, 20, 25, and 30 Gy and the other eye used as a control. The mice were clinically monitored for one year, at which time eyes were tested using anterior segment optical coherence tomography, then the mice were euthanized, and the corneas dissected. Corneal sections were stained with hematoxylin and eosin, β-galactosidase, and CK12. The results indicated that animals experiencing increased doses of radiation had increased corneal vascularization, fibrosis, and opacity and conjuctivalization and a higher number of positive results of beta-galactosidase staining, which indicates an increase in the tendency of senescence. The results of β-III tubulin staining indicated that the density of corneal stromal nerves and the subepithelial nerve plexus decreases as the dose increases. Also, as the irradiation dose increases, the central corneal thickness decreases as well.

放射治疗是头颈部恶性肿瘤的常规治疗方法之一。尽管实施了保护措施以尽量减少对辐射部位周围健康组织的有害影响，但放射性角膜病变仍然是一种普遍的并发症。我们的目的是建立一个放射性角膜病变的小鼠模型，以表征该疾病的病理生理学，并使未来确定潜在的治疗方法。36只老鼠被平均分为6组。每只小鼠的一只眼睛分别用5、10、15、20、25和30 Gray照射，另一只眼睛作为对照。临床监测1年，对小鼠进行眼前段光学相干性测试，然后对小鼠实施安乐死，解剖角膜。角膜切片苏木精、伊红、β-半乳糖苷酶和CK12染色。结果表明，辐射剂量增加的动物角膜血管化、纤维化、混浊和结合体增加，β -半乳糖苷酶染色阳性结果增多，表明衰老趋势增加。β-III微管蛋白染色结果显示，随着剂量的增加，角膜间质神经和上皮下神经丛的密度降低。同时，随着辐照剂量的增加，角膜中央厚度也减小。

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引用次数: 0

Mosaicism and intronic variants in RB1 gene revealed by next generation sequencing in a cohort of Spanish retinoblastoma patients 西班牙视网膜母细胞瘤患者的下一代测序揭示了RB1基因的嵌合体和内含子变异。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2025.110233

Gema Gomez-Mariano , Esther Hernandez-SanMiguel , Marta Fernandez-Prieto , Sheila Ramos del Saz , Beatriz Baladrón , Lidia Mirela Mielu , Daniel Rivera , Victoria Moneo , Lidia Lopez , Carlos Rodriguez-Martin , Ana Fernandez-Teijeiro Álvarez , Constantino Sabado , Eva Bermejo , Francisco Javier Alonso , Beatriz Martinez-Delgado

Constitutional variants in the RB1 gene predispose individuals to the development of Retinoblastoma (RB) and the occurrence of second tumors in adulthood. Detection of causal RB1 gene variants is essential to establish the genetic diagnosis and to performing familial studies and counseling. In our cohort of 579 Spanish RB patients, 15% of cases suspected to have a genetic origin remained negative after traditional Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) of RB1 gene, likely due to the possibility of mosaicism or non-coding variants. A specific next-generation sequencing (NGS) gene panel was designed to analyze the complete sequence of the RB1 gene. While many familial RB cases showed variants through Sanger and MLPA, the analysis of 65 available sporadic RB patients using the NGS gene panel identified a causative variant in an additional 6 of 26 (23%) bilateral cases and 6 of 39 (15.4%) unilateral cases. Seven of these cases exhibited different degrees of mosaicism (26%, 20%, 15.8%, 8%, 6%, 5.9% and 3%) while 5 cases had heterozygous deep intronic variants, all of them previously described in RB patients. Additional cases with suspected variants, not detected in blood but present in tumor tissue, were also analyzed using NGS PCR amplicons, and mosaicism was confirmed in other 10 sporadic cases. Altogether, the use of NGS increased the diagnostic yield, particularly for patients with sporadic RB in 10 bilateral cases and in 12 unilateral cases.

RB1基因的体质变异使个体易患视网膜母细胞瘤（RB）并在成年期发生第二肿瘤。因果RB1基因变异的检测对于建立遗传诊断和进行家族研究和咨询至关重要。在我们的579名西班牙RB患者队列中，在传统的Sanger测序和RB1基因的多重连接依赖探针扩增（Multiplex lig- dependent Probe Amplification， MLPA）后，15%怀疑有遗传来源的病例仍然呈阴性，可能是由于嵌合体或非编码变异的可能性。设计了一个特定的下一代测序（NGS）基因面板来分析RB1基因的完整序列。虽然许多家族性RB病例通过Sanger和MLPA显示了变异，但使用NGS基因面板对65例可用的散发性RB患者进行分析，发现26例（23%）双侧病例中有6例（23%）和39例（15.4%）单侧病例中有6例（15.4%）存在致病变异。其中7例表现出不同程度的嵌合体（26%、20%、15.8%、8%、6%、5.9%和3%），5例表现为杂合性深内含子变异，均在RB患者中有报道。在血液中未检测到但在肿瘤组织中存在的其他疑似变异病例也使用NGS PCR扩增子进行了分析，并在其他10例散发病例中证实了嵌合现象。总的来说，NGS的使用提高了诊断率，特别是对于10例双侧和12例单侧的散发性RB患者。

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引用次数: 0

Induction of age-related ocular disorders in a mouse model of pulmonary fibrosis 小鼠肺纤维化模型中年龄相关性眼部疾病的诱导。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2025.110238

Chao Wang , Xue Li , Qi Tang, Jialu Wu, Jie-Guang Chen

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease linked to aging. This study investigates potential connections between IPF and age-related eye problems using a bleomycin-induced IPF mouse model. Intratracheal administration of bleomycin induces rapid lung injury in mice, followed by IPF with characteristics of cellular senescence. IPF-injured mice had reduced amplitudes of scotopic ERG and immunostaining of visual arrestin, suggesting declined rod-related visual function. Interestingly, the mice's eyes also showed increased susceptibility to Staphylococcus aureus infections, reminiscent of the aging eyes. To determine whether an early onset of aging contributes to the eye disorders, we examined complement and senescence markers in the retina. In bleomycin-injury IPF mice, DNA damage-related senescence marker γH2AX was found in the retinal out nuclear layer where photoreceptors are located. Additionally, IPF mice displayed elevated levels of C3b, a complement fragment resulting from C3 activation that occurs frequently in aging eyes. These findings underscore the potential of IPF as a valuable mouse model for investigating early-onset age-related ocular disorders.

特发性肺纤维化（IPF）是一种与衰老有关的进行性肺部疾病。本研究利用博莱霉素诱导的 IPF 小鼠模型，探讨了 IPF 与年龄相关眼疾之间的潜在联系。气管内注射博莱霉素会导致小鼠肺部快速损伤，随后出现具有细胞衰老特征的 IPF。IPF损伤小鼠的光斑ERG振幅减小，视觉停滞素免疫染色减弱，表明与杆相关的视觉功能下降。有趣的是，小鼠的眼睛还显示出对金黄色葡萄球菌感染的敏感性增加，这让人联想到衰老的眼睛。为了确定早期衰老是否会导致眼部疾病，我们检测了视网膜中的补体和衰老标记物。在博莱霉素损伤的IPF小鼠中，在感光细胞所在的视网膜核外层发现了DNA损伤相关的衰老标记物γH2AX。此外，IPF 小鼠的 C3b 水平升高，C3b 是一种由 C3 激活产生的补体片段，经常发生在衰老的眼睛中。这些发现强调了 IPF 作为一种有价值的小鼠模型的潜力，可用于研究早期发生的与年龄相关的眼部疾病。

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引用次数: 0

TAT-N24 enhances retinal ganglion cell survival by suppressing ZBP1-PANoptosome-mediated PANoptosis in an acute glaucoma mouse model 在急性青光眼小鼠模型中，TAT-N24通过抑制zbp1 - panoptosomes介导的PANoptosis来提高视网膜神经节细胞的存活。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2025.110244

Fei Li , Qiuxiang Zhang , Yan Rong, Sifei Xiang, Junming Wang

The abrupt and substantial elevation of intraocular pressure (IOP) in acute glaucoma induces retinal ischemia/reperfusion (I/R) injury, resulting in progressive retinal ganglion cell (RGC) death and irreversible visual impairment. PANoptosis, a form of regulated cell death consisting of pyroptosis, apoptosis and necroptosis, is reported to be involved in high IOP-induced RGC death. However, the precise mechanisms of RGC death remain unclear, and neuroinflammation is considered to play a vital role. TAT-N24, a synthetic inhibitor targeting the p55 regulatory subunit of phosphatidylinositol 3-kinase (p55PIK) signaling, demonstrates anti-inflammatory effect in uveitis and may have certain neuroprotective effects. Therefore, we investigated whether TAT-N24 could shield RGCs from immunoinflammatory damage in an acute glaucoma mouse model and explored the potential mechanism associated with PANoptosis. A mouse model of acute ocular hypertension (AOH) was established. Intravitreal injection of TAT-N24 was conducted to evaluate its impact on RGC death. The expression levels of key components in PANoptosis were analyzed using RT-qPCR and Western blotting. Immunohistochemistry and immunofluorescence staining on eyeball sections were employed to assess the expression of p55PIK, Brn3a, and ionized calcium binding adaptor molecule 1 (Iba1). Retinal structure was examined by H&E staining, while cell apoptosis was evaluated by TdT-mediated dUTP nick end labeling (TUNEL). The results showed that intravitreal injection of TAT-N24 effectively alleviated RGC death and retinal damage induced by AOH injury. The key components in PANoptosis were markedly upregulated after AOH injury, while these components were significantly inhibited after TAT-N24 treatment. Moreover, the expression levels of Z-DNA-binding protein 1 (ZBP1)-PANoptosome (ZBP1, RIPK1, RIPK3, and Caspase-8), NLR family pyrin domain-containing protein 3 (NLRP3), and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes were notably elevated after AOH injury, which was significantly suppressed by TAT-N24. In conclusion, PANoptosis was involved in AOH-induced RGC death and retinal damage. TAT-N24 exhibited an anti-PANoptotic effect, protecting RGCs by inhibiting ZBP1-PANoptosome as well as NLRP3 and NLRC4 inflammasomes after AOH injury.

急性青光眼眼压（IOP）的突然和大幅升高引起视网膜缺血/再灌注（I/R）损伤，导致进行性视网膜神经节细胞（RGC）死亡和不可逆的视力损害。PANoptosis是一种由焦亡、凋亡和坏死死亡组成的受调控的细胞死亡形式，据报道与高iops诱导的RGC死亡有关。然而，RGC死亡的确切机制尚不清楚，神经炎症被认为起着至关重要的作用。TAT-N24是一种靶向磷脂酰肌醇3-激酶（p55PIK）信号p55调控亚基的合成抑制剂，在葡萄膜炎中具有抗炎作用，可能具有一定的神经保护作用。因此，我们在急性青光眼小鼠模型中研究TAT-N24是否可以保护RGCs免受免疫炎症损伤，并探讨其与PANoptosis相关的潜在机制。建立小鼠急性高眼压（AOH）模型。通过玻璃体内注射TAT-N24来评估其对RGC死亡的影响。采用RT-qPCR和Western blotting分析PANoptosis关键组分的表达水平。采用眼球切片免疫组织化学和免疫荧光染色评估p55PIK、Brn3a和离子钙结合受体分子1 （Iba1）的表达。H&E染色检测视网膜结构，tdt介导的dUTP缺口末端标记（TUNEL）检测细胞凋亡。结果表明，玻璃体内注射TAT-N24可有效减轻AOH损伤所致RGC死亡和视网膜损伤。AOH损伤后PANoptosis的关键成分明显上调，而TAT-N24处理后这些成分被显著抑制。此外，AOH损伤后，z - dna结合蛋白1 (ZBP1)-PANoptosome （ZBP1、RIPK1、RIPK3、Caspase-8）、NLR家族含pyrin结构域蛋白3 （NLRP3）、NLR家族含CARD结构域蛋白4 （NLRC4）炎症小体的表达水平显著升高，而TAT-N24可显著抑制这种表达。结论：PANoptosis参与了aoh诱导的RGC死亡和视网膜损伤。TAT-N24在AOH损伤后表现出抗panoptosome的作用，通过抑制ZBP1-PANoptosome以及NLRP3和NLRC4炎症小体来保护rgc。

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引用次数: 0

Dimethyl fumarate alleviates Staphylococcus pseudintermedius-induced cell damage by inhibiting pyroptosis and bacterial virulence 富马酸二甲酯通过抑制发热和细菌毒力减轻假中间葡萄球菌诱发的细胞损伤。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110210

Zhihao Wang , Long Guo , Pengfei Dong , Xinyi Zhu , Jianji Li , Luying Cui , Junsheng Dong , Kangjun Liu , Xia Meng , Heng Wang

The resistance of pathogenic bacteria to various clinical antibiotics is the major problem in treating bacterial keratitis. Dimethyl fumarate (DMF) has good anti-fungal and anti-inflammatory effects in fungal keratitis, but its effect on bacterial keratitis is unclear. This study aims to investigate DMF's anti-inflammatory and antibacterial effects. The pyroptosis model was constructed by intracellular infection of canine corneal epithelial cells (CCECs) with Staphylococcus pseudintermedius (S. pseudintermedius), and 200 μM DMF was added to explore its function. Western blot, ELISA, immunostaining, flow cytometry, qRT-PCR, and bacterial counts were used to examine the expression of the NLRP3-GSDMD signaling pathway, virulence genes, and oxidant mediators. 111 clinical keratitis isolates or S. pseudintermedius were treated with different concentrations of DMF to detect bacterial growth and biofilm formation. Adding DMF resulted in the inhibition of the NLRP3-GSDMD pathway while activating the NRF2 pathway. This led to a decrease in pyroptosis rate, intracellular bacteria count, and ROS content. Additionally, DMF blocked the mRNA expression of virulence genes ebpS, hlgB, siet, lukS-I, PVL, icaA, icaD, spsD, and spsL associated with S. pseudintermedius infection. Furthermore, DMF demonstrated concentration-dependent inhibition of the growth of clinical isolates and the formation of S. pseudintermedius biofilm. In conclusion, our results indicate that DMF can inhibit pyroptosis and the growth of various clinical isolates, making it a novel ophthalmic drug with anti-inflammatory and antibacterial properties.

病原菌对各种临床抗生素的耐药性是治疗细菌性角膜炎的主要问题。富马酸二甲酯（DMF）对真菌性角膜炎有良好的抗真菌和消炎作用，但对细菌性角膜炎的作用尚不明确。本研究旨在探讨 DMF 的抗炎和抗菌作用。通过犬角膜上皮细胞（CCECs）胞内感染假中间葡萄球菌（S.pseudintermedius）构建了热变态反应模型，并加入 200 μM DMF 以探索其功能。利用 Western 印迹、ELISA、免疫染色、流式细胞术、qRT-PCR 和细菌计数来检测 NLRP3-GSDMD 信号通路、毒力基因和氧化介质的表达。用不同浓度的 DMF 处理 111 株临床角膜炎分离株或假角膜炎奈瑟菌，以检测细菌的生长和生物膜的形成。加入 DMF 后，NLRP3-GSDMD 通路受到抑制，而 NRF2 通路则被激活，这导致了热变态反应率、细胞内细菌数量和 ROS 含量的下降。此外，DMF 还能阻断与伪中间体感染相关的毒力基因 ebpS、hlgB、siet、lukS-I、PVL、icaA、icaD、spsD 和 spsL 的 mRNA 表达。此外，DMF 对临床分离株的生长和伪中间肠杆菌生物膜的形成具有浓度依赖性抑制作用。总之，我们的研究结果表明，DMF 可抑制脓毒血症和各种临床分离菌的生长，是一种具有消炎和抗菌特性的新型眼科药物。

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引用次数: 0

Human embryonic stem cell-derived immunity-and-matrix-regulatory cells on collagen scaffold effectively treat rat corneal alkali burn 胶原支架上的人类胚胎干细胞衍生免疫和基质调节细胞可有效治疗大鼠角膜碱烧伤。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110164

Haimiao Lin , Baojie Guo , Zhongwen Li , Chenxin Wang , Wenyu Wu , Zhaoxiang Lu , Liu Wang , Jun Wu , Jinming Li , Jie Hao , Yun Feng

Corneal alkali burns (CAB) are a severe form of ocular injury that often leads to significant vision loss, with limited effective treatment options available beyond corneal transplantation. Immunity and matrix-regulatory cells (IMRCs) have emerged as a promising alternative due to their ability to modulate immune responses and support tissue repair. This study investigates the efficacy of IMRCs on collagen scaffolds (IMRCs-col) for treating CAB in a rat model. We developed a novel treatment combining IMRCs with a collagen scaffold to align with the ocular surface structure. In vitro analyses showed that IMRCs-col significantly upregulated the expression of immune regulatory molecules, including IL-1RA and SCF. Additionally, IMRCs-col effectively inhibited the production of pro-inflammatory cytokines (IL-8 and Gro-a/CXCL1) while promoting pro-regenerative cytokines (bFGF, HGF, and PDGF). In an animal model of CAB, IMRCs-col transplantation demonstrated substantial efficacy in restoring corneal opacity and reducing neovascularization. Histological examination revealed reduced inflammation and improved corneal tissue regeneration compared to untreated CAB. Enhanced activation of pathways associated with anti-inflammatory responses and tissue repair was observed at days 3, 7, and 21 post-treatment.

角膜碱烧伤（CAB）是一种严重的眼部损伤，通常会导致视力严重下降，而除了角膜移植外，有效的治疗方法非常有限。免疫和基质调节细胞（IMRCs）因其调节免疫反应和支持组织修复的能力而成为一种很有前景的替代疗法。本研究调查了胶原支架上的 IMRCs（IMRCs-col）在大鼠模型中治疗 CAB 的疗效。我们开发了一种新型疗法，将 IMRCs 与胶原支架相结合，使其与眼表结构相一致。体外分析表明，IMRCs-col 能显著上调免疫调节分子（包括 IL-1RA 和 SCF）的表达。此外，IMRCs-col 还有效抑制了促炎症细胞因子（IL-8 和 Gro-a/CXCL1）的产生，同时促进了促再生细胞因子（bFGF、HGF 和 PDGF）的产生。在 CAB 动物模型中，IMRCs-col 移植在恢复角膜混浊和减少新生血管方面表现出了显著的疗效。组织学检查显示，与未经治疗的 CAB 相比，炎症有所减轻，角膜组织再生得到改善。在治疗后的第 3、7 和 21 天，观察到与抗炎反应和组织修复相关的通路激活增强。

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引用次数: 0

Integrative analysis and knowledgebase construction of key candidate genes and pathways in age-related macular degeneration 老年性黄斑变性关键候选基因与通路的整合分析与知识库构建。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110177

Dongyue Wang , Tong Tang , Yayi Wang , Jing Zhao , Bairong Shen , Ming Zhang

Age-related macular degeneration is a retinal disease that severely impacts vision in the older population. Its gene-related heterogeneity has not been fully studied, increasing the burden of precise treatment, prevention and prognosis. Genetic variation and related information were collected, annotated and expanded from multiple related websites, and all the data were integrated into the online platform AMDGKB. Users can visit this database via the following link: http://amdgd.bioinf.org.cn/for their personalized applications knowledge-guided modeling and applications. This study also explored the heterogeneity of ethnicity and AMD subtypes via genetic variation, functional enrichment analysis and protein‒protein interactions.

These results suggest that VEGFA, MT2A, CCL2 and SERPINF1 play different roles in the development of AMD in different ethnic groups. The enrichment analysis also revealed differences in the pathogenesis pathways of different ethnic groups and AMD subtypes. This study highlights that genetic heterogeneity needs to be considered in the process of diagnosis and treatment. AMDGKB provides information for investigating the transformation of genetic variation during AMD progression, as well as for future personalized applications in the diagnosis and prognosis of AMD.

年龄相关性黄斑变性是一种严重影响老年人视力的视网膜疾病。其基因相关异质性尚未得到充分研究，增加了精准治疗、预防和预后的负担。从多个相关网站收集、注释和扩展遗传变异及相关信息，并将所有数据整合到在线平台AMDGKB中。用户可以通过以下链接访问此数据库：http://amdgd.bioinf.org.cn/for他们的个性化应用程序知识指导建模和应用程序。本研究还通过遗传变异、功能富集分析和蛋白-蛋白相互作用探讨了种族和AMD亚型的异质性。这些结果表明，VEGFA、MT2A、CCL2和serinf1在不同民族AMD的发生发展中起着不同的作用。富集分析还揭示了不同民族和AMD亚型的发病途径的差异。本研究强调在诊断和治疗过程中需要考虑遗传异质性。AMDGKB为研究AMD进展过程中遗传变异的转化，以及未来在AMD诊断和预后方面的个性化应用提供了信息。

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引用次数: 0

Tear inflammatory cytokine profiles in orbital inflammatory disease 眼眶炎症性疾病的泪液炎症细胞因子谱。

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110205

Terence Ang , Jessica Y. Tong , Clare Quigley , Dinesh Selva

Tear inflammatory cytokines are a novel biomarker studied in a range of ocular surface diseases, periorbital and orbital conditions. This single-centre prospective study between 2022 and 2024 aims to characterise tear cytokine profiles (Interleukin-1β [IL-1β], IL-2, IL-6, Interferon-γ [IFN-γ] and Tumour Necrosis Factor-α [TNF- α]) in orbital inflammatory disease (OID). OID patients had pre-treatment tear collection via micropipette, and cytokine analysis via multiplex bead array analysis. Thirteen healthy controls with no prior ophthalmic history were enrolled for comparison. Eighteen tear specimens from seventeen OID patients (6 males; mean age: 52.1 ± 17.1-years-old), with one repeat tear sample taken for recurrent contralateral orbital inflammation. Diagnoses included non-specific orbital inflammation (47.1%), IgG4-related orbital disease (17.6%), orbital granulomatosis with polyangiitis (5.9%), giant cell arteritis (5.9%), herpes zoster ophthalmicus with orbital apex inflammation (5.9%), viral dacryoadenitis (5.9%), bacterial dacryoadenitis (5.9%) and orbital inflammation of uncertain cause (5.9%). Overall, OID patients, and specifically those with dacryoadenitis, had greater IL-6 levels compared to controls (P = 0.038 and 0.002, respectively). OID with dacryoadenitis had higher IL-1β levels compared to those without (P = 0.029). Higher IL-6 levels were observed in idiopathic dacryoadenitis compared to healthy controls (P = 0.008, respectively). There is significant variability in tear inflammatory cytokines profiles observed in OID. IL-1β and IL-6 levels may be non-specific markers of dacryoadenitis and may be particularly elevated in idiopathic dacryoadenitis. Tear cytokines may be affected by severity, localisation and pattern of inflammation. The utility of tear cytokines in the monitoring and prognostication of OID remains to be elucidated.

泪液炎症因子是一种新的生物标志物，在一系列眼表疾病、眶周和眶内疾病中得到了研究。这项2022年至2024年的单中心前瞻性研究旨在表征眼眶炎性疾病（OID）的撕裂细胞因子谱（白介素-1β [IL-1β]、IL-2、IL-6、干扰素-γ [IFN-γ]和肿瘤坏死因子-α [TNF- α]）。治疗前用微移液管采集患者泪液，用多重头阵列分析患者细胞因子。13名没有眼科病史的健康对照进行比较。17例OID患者18例撕裂标本(男性6例；平均年龄：52.1±17.1岁)，对侧眼眶复发性炎症1例。诊断包括非特异性眼眶炎症（47.1%）、igg4相关眼眶疾病（17.6%）、眼眶肉芽肿合并多血管炎（5.9%）、巨细胞动脉炎（5.9%）、带状疱疹伴眼眶尖炎（5.9%）、病毒性泪腺炎（5.9%）、细菌性泪腺炎（5.9%）和不明原因眼眶炎症（5.9%）。总体而言，OID患者，特别是泪腺炎患者，与对照组相比，IL-6水平更高（P分别=0.038和0.002）。泪腺炎患者的IL-1β水平高于无泪腺炎患者（P=0.029）。与健康对照组相比，特发性泪腺炎患者IL-6水平较高（P= 0.008）。在OID中观察到泪液炎症细胞因子谱有显著的变异性。IL-1β和IL-6水平可能是泪腺炎的非特异性标志物，在特发性泪腺炎中可能特别升高。撕裂细胞因子可能受炎症的严重程度、局部和模式的影响。泪液细胞因子在OID监测和预测中的作用仍有待阐明。

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引用次数: 0