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O-GlcNAcylation promotes astroglial-mesenchymal transition via the connexin43 pathway under high-glucose conditions 在高糖条件下,o - glcn酰化通过connexin43途径促进星形胶质细胞-间质转化。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110206
Guodong Liu , Hui Li , Le Feng , Min Li , Peng Gao , Fang Wang
This study aimed to investigate the effects of O-linked N-acetylglucosamine modification (O-GlcNAcylation) on astroglial-mesenchymal transition through connexin43 (Cx43) pathway under high-glucose conditions. The primary rat astrocytes were cultured under normal and high-glucose conditions, and level of GFAP, α-SMA and Cx43 was investigated. To explore the influence of O-GlcNAcylation on astroglial-mesenchymal transition, Thiamet G treatment was employed to enhance O-GlcNAcylation, while Alloxan was used to decrease it. Cx43 knockdown was acquired through lentivirus constructs to explore its role in astrocyte transition. The levels of GFAP and α-SMA expressions were examined, while astrocyte proliferation was evaluated using the CCK-8 assay, and migration was assessed through wound healing assays. The results showed that primary rat astrocytes were identified by GFAP antibody staining. Under high-glucose conditions, the levels of GFAP, α-SMA, and Cx43 increased, as confirmed by Western blot and immunofluorescence. O-GlcNAcylation augmentation induced by Thiamet G treatment significantly increased the expression of GFAP, α-SMA, and Cx43 compared to both normal and high-glucose conditions. Conversely, the inhibition of O-GlcNAcylation reversed the high-glucose-induced increase in GFAP and α-SMA. Cx43 knockout led to the downregulation of GFAP and α-SMA compared to high-glucose and O-GlcNAcylation-augmented conditions. Additionally, levels of O-GlcNAcylation and VEGF were reduced in Cx43 knockout group. Consistently, CCK8 and wound healing assays demonstrated that Cx43 knockout could inhibit astrocyte proliferation and migration compared to the high-glucose and O-GlcNAcylation augmented groups. These findings demonstrate that astroglial-mesenchymal transition occurs under high-glucose conditions, and can be promoted by O-GlcNAcylation augmentation, but suppressed by Cx43 knockout. The study underscores the significant role of Cx43 in this transition and its potential involvement in diabetic complications.
本研究旨在探讨在高葡萄糖条件下,O-连接的N-乙酰葡糖胺修饰(O-GlcNAcylation)通过连接蛋白43(Cx43)通路对星形胶质细胞-间充质转化的影响。在正常和高糖条件下培养原代大鼠星形胶质细胞,并检测其 GFAP、α-SMA 和 Cx43 的水平。为了探讨 O-GlcNAcylation 对星形胶质细胞-间充质转化的影响,采用 Thiamet G 处理来增强 O-GlcNAcylation,而采用 Alloxan 来降低 O-GlcNAcylation。通过慢病毒构建获得 Cx43 基因敲除,以探讨其在星形胶质细胞转化中的作用。研究人员检测了 GFAP 和 α-SMA 的表达水平,使用 CCK-8 试验评估了星形胶质细胞的增殖,并通过伤口愈合试验评估了迁移。结果显示,原代大鼠星形胶质细胞可通过 GFAP 抗体染色识别。在高葡萄糖条件下,GFAP、α-SMA 和 Cx43 的水平升高,这一点已通过 Western 印迹和免疫荧光证实。与正常和高糖条件相比,Thiamet G 处理诱导的 O-GlcNAcylation 增强可显著增加 GFAP、α-SMA 和 Cx43 的表达。相反,抑制 O-GlcNAcylation 可逆转高糖诱导的 GFAP 和 α-SMA 的增加。与高葡萄糖和 O-GlcNAcylation 增强条件相比,Cx43 基因敲除导致 GFAP 和 α-SMA 下调。此外,Cx43基因敲除组的O-GlcNAcylation和VEGF水平也有所降低。同样,CCK8 和伤口愈合试验表明,与高葡萄糖组和 O-GlcNAcylation 增强组相比,Cx43 基因敲除可抑制星形胶质细胞的增殖和迁移。这些研究结果表明,星形胶质细胞-间充质转化发生在高葡萄糖条件下,O-GlcNAcylation 增强可促进这种转化,但 Cx43 基因敲除可抑制这种转化。该研究强调了 Cx43 在这种转变中的重要作用及其在糖尿病并发症中的潜在参与。
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引用次数: 0
Morphological characterization of retinal development from birth to adulthood via retinal thickness assessment in mice: A systematic review 通过视网膜厚度评估小鼠从出生到成年视网膜发育的形态学特征:一项系统综述。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110229
Simon Brais-Brunet , Caroline Boudoux , Mathieu Dehaes
The morphology and thickness of the retinal layers are valuable biomarkers for retinal health and development. The retinal layers in mice are similar to those in humans; thus, a mouse is appropriate for studying the retina. The objectives of this systematic review were: (1) to describe normal retinal morphology quantitatively using retinal layer thickness measured from birth to age 6 months in healthy mice; and (2) to describe morphological changes in physiological retinal development over time using the longitudinal (in vivo) and cross-sectional (ex vivo) data from the included studies. A PubMed search was conducted for articles published from to 1980–2024 that included quantitative data. Prior to sexual maturity, an increase in the total retinal and inner plexiform layer thicknesses were observed, with a decrease in the inner nuclear layer thickness. After sexual maturity, an asymptotic decrease in thickness was observed up to age 6 months in all layers; during this period, no significant changes were observed in the outer nuclear layer or nerve fiber layer/ganglion cell layer complex. Potential sources of variability and inconsistency among the studies included differences in imaging modality, animal strain, measurement timing, and retinal segmentation/assignment techniques. These findings highlight the importance of including a control group in experimental designs and providing comparative data for further investigations.
视网膜层的形态和厚度是视网膜健康和发育的重要生物标志物。老鼠的视网膜层与人类相似;因此,用老鼠来研究视网膜是合适的。本系统综述的目的是:(1)利用健康小鼠从出生到6个月的视网膜层厚度定量描述正常视网膜形态;(2)利用所纳入研究的纵向(体内)和横断面(离体)数据描述视网膜生理发育随时间的形态学变化。PubMed检索了1980-2024年间发表的包含定量数据的文章。性成熟前,观察到视网膜和内丛状层总厚度增加,内核层厚度减少。性成熟后,直到6个月大,所有层的厚度都逐渐减少;在此期间,外核层或神经纤维层/神经节细胞层复合物未见明显变化。研究之间的变异性和不一致性的潜在来源包括成像方式、动物品系、测量时间和视网膜分割/分配技术的差异。这些发现强调了在实验设计中包括对照组和为进一步研究提供比较数据的重要性。
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引用次数: 0
Accumulation of autophagosomes in aging human photoreceptor cell synapses 衰老的人感光细胞突触中自噬体的积累。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2025.110240
Tapas C. Nag
Autophagy is common in the aging retinal pigment epithelium (RPE). A dysfunctional autophagy in aged RPE is implicated in the pathogenesis of age-related macular degeneration. Aging human retina accompanies degenerative changes in photoreceptor mitochondria. It is not known how the damaged mitochondria are handled by photoreceptor cells with aging. This study examined donor human retinas (age: 56–94 years; N = 12) by transmission electron microscopy to find mitochondrial dynamics and status of autophagy in macular photoreceptor cells. Observations were compared between the relatively lower age (56–78 years) and aged retinas (80–94 years). Mitochondrial fusion was predominant in photoreceptor inner segments (ellipsoids), but rarely seen in the synaptic terminals. Also, fusion became widespread with progressive aging in ellipsoids (12% and 21% between rods and cones at tenth decade, respectively). More importantly, it was found that the photoreceptor synaptic mitochondria altered significantly with aging (swelling and loss of cristae), compared to those in ellipsoids that became dark and condensed. The damaged synaptic mitochondria were sequestered inside autophagosomes, whose frequency was higher in aged photoreceptors, being 34% in cone and 24% in rod terminals, at tenth decade. However, autolysosomes/residual bodies were rare, and thus the aged photoreceptor synaptic terminals harboured many autophagosomes, the possible reasons for which are discussed. Such age-related altered mitochondrial population and defective autophagy in synaptic terminals may influence photoreceptor survival in late aging.
自噬在老化的视网膜色素上皮(RPE)中很常见。老年RPE中功能失调的自噬与年龄相关性黄斑变性的发病机制有关。老化的人类视网膜伴随着光感受器线粒体的退行性变化。随着年龄的增长,光感受器细胞如何处理受损的线粒体尚不清楚。本研究检查了供体人类视网膜(年龄:56-94岁;N=12)透射电镜观察黄斑感光细胞线粒体动态及自噬状态。比较了年龄相对较低(56-78岁)和年龄较大(80-94岁)的视网膜的观察结果。线粒体融合主要发生在光感受器内节段(椭球体),但在突触末端很少见到。此外,随着椭球体的逐渐老化,融合变得普遍(在第10个十年中,杆状体和锥状体之间分别为12%和21%)。更重要的是,与变暗和浓缩的椭球体相比,光感受器突触线粒体随着年龄的增长(嵴肿胀和丧失)发生了显著变化。受损的突触线粒体被隔离在自噬体内,在衰老的光感受器中,自噬体的频率更高,在第10年,锥体端为34%,杆端为24%。然而,自噬体/残体很少,因此老化的光感受器突触末端含有许多自噬体,并讨论了其可能的原因。这种与年龄相关的线粒体种群改变和突触末端的自噬缺陷可能影响晚期衰老的光感受器存活。
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引用次数: 0
A system for producing controlled elevation of intraocular pressure in awake Brown Norway rats 清醒褐挪威大鼠眼内压可控升高系统的研究。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2025.110237
John C. Morrison, William Cepurna, Eliesa Ing, Elaine Johnson, Aryana Abtin, Susan Wentzien, Elizabeth White, Diana C. Lozano
Animal models that help us understand how elevated intraocular pressure (IOP) causes axonal injury will lead to new glaucoma therapies. Because reliable measurements are difficult to obtain in chronic models, we developed the controlled elevation of IOP (CEI) approach. Here, a cannula connected to an elevated balanced salt solution (BSS) reservoir is inserted into the anterior chamber of anesthetized Brown Norway rats. The extent and duration of IOP exposure is controlled by adjusting the reservoir height. We now describe a method for creating CEI in awake animals. A Pinport, which has a silicone plug that can be penetrated repeatedly, is modified, attached to the skull, and connected to a microcannula that is implanted in the posterior chamber. To elevate IOP, BSS from a reservoir is allowed to flow through a pressure transducer to a swivel-mounted tether and injector. The injector is placed on the Pinport, bypassing the need for anterior chamber cannulation and general anesthesia during CEI. The surgical technique and equipment required for implantation are described, as well as the equipment and methods for performing awake CEI in several animals at a time. The ability of this system to control the level of IOP is demonstrated by TonoLab measurement, and by comparing reservoir (Pinport) pressures to direct measurement using an independent anterior chamber cannula and transducer. We also demonstrate that IOP elevation can be maintained over several hours. Specific pitfalls during and after surgical implantation are highlighted to help other researchers adopt these techniques.
帮助我们了解眼压升高(IOP)如何导致轴突损伤的动物模型将带来新的青光眼治疗方法。由于在慢性模型中难以获得可靠的测量,我们开发了控制IOP升高(CEI)方法。在这里,一根连接到高平衡盐溶液(BSS)储存器的插管被插入麻醉的布朗挪威大鼠的前房。通过调节储层高度来控制IOP暴露的程度和持续时间。我们现在描述一种在清醒的动物中产生CEI的方法。Pinport有一个硅胶塞,可以反复插入,经过修改后附着在颅骨上,并与植入后房的微套管相连。为了提高IOP,油藏中的BSS可以通过压力传感器流入旋转系索和注入器。注射器放置在Pinport上,在CEI期间不需要前房插管和全身麻醉。本文描述了植入所需的手术技术和设备,以及同时对几只动物进行清醒CEI的设备和方法。TonoLab测量证明了该系统控制IOP水平的能力,并通过将储层(Pinport)压力与使用独立前房套管和换能器直接测量的压力进行了比较。我们也证明IOP升高可以维持几个小时。强调了手术植入期间和之后的具体陷阱,以帮助其他研究人员采用这些技术。
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引用次数: 0
Choroidal thickening and retinal dopamine increase in mice at high altitude 高海拔小鼠脉络膜增厚和视网膜多巴胺增加。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2025.110241
Cong Han , Yuting Li , Xingxing Zheng , Jianping Zhang , Xin Zhao , Keke Ge , Guonian Li , Yi Yang , Wenfang Zhang
The mechanisms underlying the low incidence of myopia at high altitudes remain unclear. Choroidal thickness and the dopaminergic system have been shown to be closely associated with myopia development. This study aimed to investigate the effects of high altitude exposure on choroidal thickness and the dopaminergic system. Mice were subjected to acute hypobaric hypoxia at an altitude of 5000 m for durations ranging from 2 to 72 h, as well as chronic exposure at an altitude of 3670 m for a period of 3 months. Choroidal thickness was assessed using hematoxylin and eosin (H&E) staining of ocular tissues. The retinal dopamine (DA) levels and its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were quantified via high-performance liquid chromatography (HPLC). The expression levels of dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R) were evaluated using immunofluorescence techniques. Study results indicated that choroidal thickness significantly increased after 6 h of high altitude exposure. Retinal dopamine levels showed significant increases in both the 2–10 h and 3 months high altitude groups. Conversely, retinal DOPAC levels decreased in the 2 h and 4 h groups but increased significantly at 72 h. Following high altitude exposure, D1R expression correlated positively with DA levels, while D2R expression exhibited a negative correlation. In conclusion, high-altitude exposure is associated with significant increases in choroidal thickness and retinal DA levels, with D1R and D2R expression patterns varying in response to changes in retinal DA. These findings may represent a key molecular mechanism contributing to the lower incidence of myopia observed at high altitudes.
高海拔地区近视发生率低的原因尚不清楚。脉络膜厚度和多巴胺能系统已被证明与近视的发展密切相关。本研究旨在探讨高海拔暴露对脉络膜厚度和多巴胺能系统的影响。小鼠在海拔5000米处急性低压缺氧2 ~ 72小时,在海拔3670米处慢性暴露3个月。采用眼组织苏木精和伊红(H&E)染色评估脉络膜厚度。采用高效液相色谱法测定大鼠视网膜多巴胺(DA)及其主要代谢物3,4-二羟基苯基乙酸(DOPAC)水平。采用免疫荧光技术检测多巴胺D1受体(D1R)和多巴胺D2受体(D2R)的表达水平。研究结果表明,高海拔暴露6 h后,脉络膜厚度显著增加。视网膜多巴胺水平在2-10小时和3个月的高海拔组中均显着增加。相反,视网膜DOPAC水平在2 h和4 h组下降,但在72 h组显著升高。高海拔暴露后,D1R表达与DA水平呈正相关,而D2R表达呈负相关。综上所述,高海拔暴露与脉络膜厚度和视网膜DA水平的显著增加有关,D1R和D2R的表达模式随着视网膜DA的变化而变化。这些发现可能代表了高海拔地区近视发生率较低的关键分子机制。
{"title":"Choroidal thickening and retinal dopamine increase in mice at high altitude","authors":"Cong Han ,&nbsp;Yuting Li ,&nbsp;Xingxing Zheng ,&nbsp;Jianping Zhang ,&nbsp;Xin Zhao ,&nbsp;Keke Ge ,&nbsp;Guonian Li ,&nbsp;Yi Yang ,&nbsp;Wenfang Zhang","doi":"10.1016/j.exer.2025.110241","DOIUrl":"10.1016/j.exer.2025.110241","url":null,"abstract":"<div><div>The mechanisms underlying the low incidence of myopia at high altitudes remain unclear. Choroidal thickness and the dopaminergic system have been shown to be closely associated with myopia development. This study aimed to investigate the effects of high altitude exposure on choroidal thickness and the dopaminergic system. Mice were subjected to acute hypobaric hypoxia at an altitude of 5000 m for durations ranging from 2 to 72 h, as well as chronic exposure at an altitude of 3670 m for a period of 3 months. Choroidal thickness was assessed using hematoxylin and eosin (H&amp;E) staining of ocular tissues. The retinal dopamine (DA) levels and its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were quantified via high-performance liquid chromatography (HPLC). The expression levels of dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R) were evaluated using immunofluorescence techniques. Study results indicated that choroidal thickness significantly increased after 6 h of high altitude exposure. Retinal dopamine levels showed significant increases in both the 2–10 h and 3 months high altitude groups. Conversely, retinal DOPAC levels decreased in the 2 h and 4 h groups but increased significantly at 72 h. Following high altitude exposure, D1R expression correlated positively with DA levels, while D2R expression exhibited a negative correlation. In conclusion, high-altitude exposure is associated with significant increases in choroidal thickness and retinal DA levels, with D1R and D2R expression patterns varying in response to changes in retinal DA. These findings may represent a key molecular mechanism contributing to the lower incidence of myopia observed at high altitudes.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110241"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002147","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
The vectors went in two-by-two: Transduction efficiency and tolerability of dual and triple rAAV vector delivery following intravitreal injection for genome-editing applications 载体分为两部分:在基因组编辑应用的玻璃体内注射后,双重和三重rAAV载体传递的转导效率和耐受性。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110223
Rachel L. Fehrman , Kristina J. Chern , Kyle P. Stoltz , Daniel M. Lipinski
Genome or prime editing has become a promising tool for the treatment of hereditary disorders affecting the inner retina, such as dominant optic neuropathies. In vivo delivery of gene editors, such as Cas9, is typically achieved using recombinant adeno-associated virus (rAAV) vectors, which have a broad range of cellular tropisms and are well tolerated following intravitreal administration. Owing to the large size of gene editing constructs and the limited carrying capacity of rAAV (<5.1 kb) it is unfortunately usually necessary to split therapeutic transgene cassettes across multiple co-administered vector genomes. While the efficiency with which multiple vector genomes recombine following cellular entry has been studied extensively, another potentially limiting factor is the likelihood of target cells (e.g. retinal ganglion cells) receiving two or more vectors containing genomes that correspond to the full-length expression cassette when recombined. In this study we examine the efficiency with which two or more vector genomes transduce various retinal cell types following intravitreal administration. rAAV2/2[MAX] vectors expressing individual fluorescent reporters (GFP, BFP or mCherry) were co-injected intravitreally singly or in combination (dual or triple), allowing the extent of co-transduction to be assessed through multimodal in vivo imaging, electroretinography, flow cytometry and post-mortem histology. We find that intravitreal co-administration of vectors containing multiple genomes is well tolerated – with no observed alterations in retinal thickness or ERG amplitudes – but that co-transduction efficiency decreases significantly with increasing genome number. As such co-transduction of multiple vectors may be a major bottleneck limiting gene editing of inherited disorders affecting the inner retina.
基因组或引体编辑已成为治疗影响内视网膜的遗传性疾病(如显性视神经病变)的一种很有前途的工具。基因编辑器(如Cas9)的体内递送通常使用重组腺相关病毒(rAAV)载体来实现,这种载体具有广泛的细胞趋向性,并且在玻璃体内给药后耐受性良好。由于基因编辑构建体的体积较大,rAAV (
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引用次数: 0
Protective effects of different exercise modalities on oxidative stress in animal models of high intraocular pressure and diabetes 不同运动方式对高眼压和糖尿病动物模型氧化应激的保护作用。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110216
Sabrina Nau da Silva Piazza , Paula Bortoluzzi Canteiro , Natalia dos Santos Tramontin , Giulia Strapazzon , Vanessa de Moraes Andrade , Alexandre Pastoris Muller
High intraocular pressure (HIOP) and high glucose levels are associated with oxidative stress. Although physical exercise protects against oxidative damage, its specific impact on eye health remains unclear. Thus, this study aimed to assess the impact of physical exercise on the oxidative status of whole eyes in male Swiss mice subjected to HIOP model and cafeteria diet (CD). In experiment one, mice were divided into sedentary, aerobic, and strength (four-week physical exercise) groups and subjected to an HIOP/ischemia model. In experiment two, mice were submitted to CD and voluntary physical exercise for 18 weeks, according to the following groups: sedentary control, sedentary CD, exercise control, and exercise CD. Experiment one revealed elevated 2′,7′-dichlorodihydrofluorescein (DCFH) levels in aerobic group, which decreased in all groups after ischemia. Nitrite levels were decreased on strength than in sedentary group. The superoxide dismutase (SOD) activity did not change in all treatments. Although catalase (CAT) activity increased in aerobic and strength groups, and after ischemia in all groups. In experiment two, the sedentary CD group presented higher body weight than the other groups. DCFH levels were increased in the exercise control and reduced in the exercise CD compared with the other groups. CAT activity and sulfhydryl groups were decreased, while protein carbonylation was increased in the sedentary CD group compared with the other groups. Thus, these results suggested that physical exercise promoted antioxidant effects on eyes exposed to an HIOP model and CD.
高眼压(HIOP)和高血糖水平与氧化应激有关。虽然体育锻炼可以防止氧化损伤,但它对眼睛健康的具体影响尚不清楚。因此,本研究旨在评估体育锻炼对HIOP模型和自助饮食(CD)雄性瑞士小鼠全眼氧化状态的影响。实验一,将小鼠分为久坐组、有氧组和力量组(4周体育锻炼),建立HIOP/缺血模型。实验二,小鼠连续18周进行CD和自愿体育锻炼,分为久坐对照组、久坐CD组、运动对照组和运动CD组。实验一显示有氧组小鼠2’,7’-二氯二氢荧光素(DCFH)水平升高,缺血后各组小鼠DCFH水平均下降。与久坐组相比,体力组亚硝酸盐水平降低。超氧化物歧化酶(SOD)活性在各处理中均无明显变化。虽然过氧化氢酶(CAT)活性在有氧组和力量组以及缺血后均有所增加。在实验二中,久坐的乳糜泻组的体重高于其他组。与其他组相比,运动对照组的DCFH水平升高,运动CD组的DCFH水平降低。与其他组相比,久坐CD组的CAT活性和巯基降低,而蛋白质羰基化增加。因此,这些结果表明,体育锻炼促进了暴露于HIOP模型和CD的眼睛的抗氧化作用。
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引用次数: 0
Photobiomodulation inhibits retinal degeneration in diabetic mice through modulation of stem cell mobilization and gene expression 光生物调节通过调节干细胞动员和基因表达抑制糖尿病小鼠视网膜变性。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110218
Jingyan Ge , Yinan Zhang , Ling Han , Liangliang Zhao , Hongwei Zhao , Dan Qiao , Yan Cheng
The number of people suffering from type 2 diabetes (DM2) is increasing and over 30 percent of DM2 patients will develop diabetic retinopathy (DR). Available therapeutic approaches for DR have their limitations. It is of great significance to search for other effective alternate therapeutic approaches. The present study aimed to explore the beneficial effects of photobiomodulation (PBM) on the diabetic retinopathy and underlying mechanisms. Streptozotocin was administered to male mice to establish diabetic model. The mice in the diabetic group (DM) received no treatment, and the mice in DM + PBM group received LED illumination (wavelength 670 nm) once a day for 20 consecutive weeks. Retinal vessel degenerate changes, the expression levels of E-Cadherin, N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α in retina, the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 were determined. PBM could significantly inhibit the degenerative change of diabetic retinal vessels, decrease the expression levels of E-Cadherin and N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α and increase VEGF mRNA levels in retina. PBM could also increase the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 in diabetic mice. PBM at 4 min/day for 20 consecutive weeks significantly inhibit the degenerative change of diabetic retinal vessels, and PBM is likely to produce its beneficial effects on the retina through promoting the migration of bone marrow stem cells to circulation and diabetic retinal tissue. The present study provides a new therapeutic direction and experimental foundation for the treatment of diabetic retinopathy.
2型糖尿病(DM2)患者的数量正在增加,其中超过30%的DM2患者将发展为糖尿病视网膜病变(DR)。DR的现有治疗方法有其局限性。寻找其他有效的替代治疗方法具有重要意义。本研究旨在探讨光生物调节(PBM)对糖尿病视网膜病变的有益作用及其机制。采用链脲佐菌素建立雄性小鼠糖尿病模型。糖尿病组(DM)小鼠不进行任何治疗,DM+PBM组小鼠接受LED照明(波长670nm),每天1次,连续20周。检测大鼠视网膜血管变性变化,视网膜E-Cadherin、N-Cadherin表达水平及c-kit、CXCR4、MYPT1、SCF、SDF1-α mRNA水平,外周血SDF-1α、SCF水平及表达c-kit、SCF -1的LSK细胞数量。PBM能显著抑制糖尿病视网膜血管的退行性改变,降低E-Cadherin、N-Cadherin的表达水平以及c-kit、CXCR4、MYPT1、SCF、SDF1-α mRNA水平,升高VEGF mRNA水平。PBM还能增加糖尿病小鼠外周血中SDF-1α和SCF的水平以及表达c-kit和sca-1的LSK细胞的数量。连续20周,4分钟/天的PBM显著抑制糖尿病视网膜血管的退行性改变,PBM可能是通过促进骨髓干细胞向循环和糖尿病视网膜组织的迁移来产生其对视网膜的有益作用。本研究为糖尿病视网膜病变的治疗提供了新的治疗方向和实验基础。
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引用次数: 0
In Memoriam: David S. Papermaster (1937–2024)
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.exer.2024.110184
Dean Bok, Steven J. Fliesler
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引用次数: 0
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 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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Experimental eye research
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