Experimental eye research最新文献_第6页

Resveratrol alleviated diabetic retinal neuronal ferroptosis induced by high glucose through inhibiting HIF-1α and HMOX1 pathway 白藜芦醇通过抑制HIF-1α和HMOX1通路减轻高糖诱导的糖尿病视网膜神经元铁下垂。

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-17 DOI: 10.1016/j.exer.2026.110872

Meng Ye , Yan Jiang , Hongya Gong , Chaowu Wu , Tao Li , Xuhui Chen

Diabetic retinopathy (DR) is a common complication of diabetes mellitus that can cause blindness and affect the life quality of patients. Diabetic retinal neurodegeneration (DRN) caused by high glucose might be the earlier pathological change preceding vascular injury. Resveratrol has been showed to have therapeutic effects on DRN but the mechanism remains unclear. Ferroptosis is a new form of regulated cell death and has been found to be involved in DRN. In this study, we found genetic relationship between resveratrol and ferroptosis in DRN pathogenesis using bioinformatics analysis and demonstrated HIF-1α and HMOX1 as the hub genes. Our study established in vitro model of DRN in high-glucose cultured SH-SY5Y cells and found ferroptosis processes characterized of reactive oxygen species (ROS) accumulation and cellular mitochondrial damage along with upregulation of HIF-1α and HMOX1. Application of resveratrol alleviated high glucose-induced ferroptosis phenotypes in SH-SY5Y cells through inhibiting HIF-1α and HMOX1. We also confirmed ferroptosis process and RGC damage in diabetic (db/db) mouse model. The upregulation of HIF-1α and HMOX1 was also found in diabetic mouse retina. By resveratrol gavage, RGC damage in diabetic (db/db) mouse model was alleviated and the expression level of HIF-1α and HMOX1 in retina was decreased. Our study revealed the involvement of ferroptosis process in retinal neurodegeneration and might provide new insights into neuroprotective interventions in diabetic retinopathy.

糖尿病视网膜病变（DR）是糖尿病常见的并发症，可导致失明，影响患者的生活质量。糖尿病性视网膜神经变性（DRN）可能是血管损伤前的早期病变。白藜芦醇已被证明对DRN有治疗作用，但其机制尚不清楚。铁下垂是一种新的受调控的细胞死亡形式，已被发现与DRN有关。本研究通过生物信息学分析发现了白藜芦醇与DRN发病机制中铁ptosis的遗传关系，并证实HIF-1α和HMOX1为中心基因。我们在高糖培养的SH-SY5Y细胞中建立了DRN体外模型，发现了以活性氧（ROS）积累和细胞线粒体损伤为特征的铁死亡过程，并伴有HIF-1α和HMOX1的上调。白藜芦醇通过抑制HIF-1α和HMOX1减轻高糖诱导的SH-SY5Y细胞铁下垂表型。我们还证实了糖尿病小鼠（db/db）模型的铁下垂过程和RGC损伤。HIF-1α和HMOX1在糖尿病小鼠视网膜中表达上调。白藜芦醇灌胃可减轻糖尿病小鼠RGC损伤（db/db），降低视网膜HIF-1α和HMOX1的表达水平。我们的研究揭示了铁下垂过程参与视网膜神经变性，并可能为糖尿病视网膜病变的神经保护干预提供新的见解。

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引用次数: 0

Retinal morphology in spinocerebellar ataxia type 1 (SCA1) mice: A stereological analysis across different age groups 脊髓小脑性共济失调1型（SCA1）小鼠的视网膜形态学：不同年龄组的立体学分析

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-16 DOI: 10.1016/j.exer.2026.110869

Olena Yakushko , Jan Cendelin , Zbynek Tonar , Yaroslav Kolinko

Spinocerebellar ataxia type 1 (SCA1) affects not only the cerebellum but also the retina; however, retinal pathology remains poorly characterised in murine models of SCA1. To fill this gap, we performed a comprehensive stereological analysis of the retinal structure of SCA1^154Q/2Q knock-in mice and their healthy SCA1^2Q/2Q littermates at 6 and 10 months of age. We compared animals across genotypes at each age and across ages within each genotype. Using unbiased stereology, we quantified the total retinal volume, volumes of individual retinal layers, total photoreceptor numbers, numbers of rods and cones, and total cell numbers in the inner nuclear and ganglion cell layers. Structural abnormalities, including disorganisation of photoreceptor outer segments and reduced volumes of both photoreceptor inner and outer segments, were evident in SCA1 mice as early as 6 months. By 10 months, these alterations had progressed, with a decrease in the number of ganglion cells and a reduced proportion of cones among the total photoreceptors. Wild-type mice also exhibited age-related changes, but the pattern and magnitude differed, suggesting distinct mechanisms of normal ageing versus SCA1-related neurodegeneration. Our findings demonstrate that retinal remodelling in SCA1 mice parallels changes observed in human patients, validating this model for investigating visual system involvement in SCA1. These results emphasize the need to consider retinal pathology when interpreting behavioural or motor deficits and in designing future preclinical interventions.

脊髓小脑性共济失调1型（SCA1）不仅影响小脑，也影响视网膜；然而，在小鼠SCA1模型中，视网膜病理特征仍然很差。为了填补这一空白，我们对SCA1154Q/2Q敲入小鼠及其6个月和10个月大的健康SCA12Q/2Q窝鼠的视网膜结构进行了全面的立体分析。我们比较了不同年龄的不同基因型的动物和不同年龄的不同基因型的动物。利用无偏立体学，我们量化了视网膜的总体积，单个视网膜层的体积，总光感受器数量，视杆细胞和视锥细胞的数量，以及细胞核和神经节细胞层的总细胞数量。SCA1小鼠早在6个月时就出现了明显的结构异常，包括光感受器外节的紊乱和光感受器内外节的体积减小。到10个月时，这些变化已经进展，神经节细胞数量减少，视锥细胞在总光感受器中的比例减少。野生型小鼠也表现出与年龄相关的变化，但模式和幅度不同，表明正常衰老与sca1相关的神经变性的不同机制。我们的研究结果表明，SCA1小鼠的视网膜重塑与人类患者观察到的变化相似，验证了研究SCA1视觉系统参与的模型。这些结果强调，在解释行为或运动缺陷以及设计未来的临床前干预措施时，需要考虑视网膜病理学。

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引用次数: 0

TLR9-mediated activation of the NLRP3 inflammasome in Fusarium solani-induced keratitis tlr9介导的NLRP3炎性小体在茄灰镰刀菌诱导的角膜炎中的激活

IF 2.7 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research

Pub Date : 2026-01-16 DOI: 10.1016/j.exer.2026.110867

Yanqing Zhang , Yi Lin , Yani Zhang , Hanfeng Tang, Jianzhang Hu, Bing Wang

Toll-like receptor 9 (TLR9) is a crucial innate immune receptor that recognises pathogenic DNA and initiates downstream inflammatory signaling, yet its function in fungal keratitis remains poorly defined. This study aimed to clarify the specific role of TLR9 in Fusarium solani (F. solani) –induced keratitis and to provide mechanistic insights for targeted therapy. A murine model of F. solani keratitis was established to examine the expression and regulation of TLR9 and NLRP3. RNA sequencing, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence were used to assess gene and protein expression. The activities of TLR9 and NLRP3 were modulated by adeno-associated virus short hairpin RNA (AAV-shRNA), small interfering RNA (siRNA), and pharmacological agents (Nig and MCC950). Disease severity and histopathological alterations were evaluated by slit-lamp examination, clinical scoring, and hematoxylin–eosin staining, while protein interactions were analysed through molecular docking and immunocolocalization. TLR9 and NLRP3 were markedly up-regulated in F. solani–infected corneas. TLR9 silencing suppressed nuclear factor κB (NF-κB) and NLRP3 activation, thereby mitigating corneal inflammation, reducing stromal oedema, limiting inflammatory cell infiltration, and lowering IL-1β production. Pharmacological inhibition of NLRP3 with MCC950 produced similar protective effects, whereas activation by nigericin reversed these benefits. In conclusion, TLR9 functions as a pivotal upstream regulator of the NLRP3 inflammasome in F. solani keratitis. These findings uncover a mechanistic link between TLR9 signaling and inflammasome-mediated inflammation, highlighting TLR9 as a potential immunomodulatory target for fungal keratitis therapy.

toll样受体9 （TLR9）是一种重要的先天免疫受体，可识别致病性DNA并启动下游炎症信号，但其在真菌性角膜炎中的功能仍不明确。本研究旨在阐明TLR9在梭兰镰刀菌（F. solani）诱导的角膜炎中的具体作用，并为靶向治疗提供机制见解。建立梭兰氏角膜炎小鼠模型，检测TLR9和NLRP3的表达和调控。采用RNA测序、定量实时聚合酶链反应（qRT-PCR）、Western blotting和免疫荧光法评估基因和蛋白的表达。TLR9和NLRP3的活性受腺相关病毒短发夹RNA （AAV-shRNA）、小干扰RNA （siRNA）和药物（Nig和MCC950）的调控。通过裂隙灯检查、临床评分和苏木精-伊红染色评估疾病严重程度和组织病理学改变，通过分子对接和免疫共定位分析蛋白质相互作用。TLR9和NLRP3在梭兰梭菌感染的角膜中显著上调。TLR9沉默可抑制核因子κB （NF-κB）和NLRP3的激活，从而减轻角膜炎症，减少间质水肿，限制炎症细胞浸润，降低IL-1β的产生。MCC950对NLRP3的药理学抑制产生了类似的保护作用，而尼日利亚菌素的激活则逆转了这些益处。综上所述，TLR9在梭氏角膜炎中作为NLRP3炎性体的关键上游调节因子发挥作用。这些发现揭示了TLR9信号与炎症小体介导的炎症之间的机制联系，突出了TLR9作为真菌性角膜炎治疗的潜在免疫调节靶点。

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引用次数: 0

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

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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。

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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。

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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。

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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。

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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。

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