EXPERIMENTAL EYE RESEARCH 的主要目标是发表关于眼睛和眼组织实验生物学各个方面的原创研究论文，旨在确定正常功能和/或疾病的机制。包括细胞生物学、发育生物学、遗传学、分子生物学、生理学、生物化学、生物物理学、免疫学或微生物学等学科的眼组织研究是最受欢迎的。纯临床或眼科外科领域的手稿不适合提交给 EXPERIMENTAL EYE RESEARCH，如果收到，将不经审查退回。

The primary aim of Experimental Eye Research is to publish original research papers on various aspects of experimental biology of the eye and its tissues, with the goal of elucidating the mechanisms of normal function and/or disease. The journal particularly welcomes studies on ocular tissues that involve disciplines such as cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology, or microbiology. Please note that manuscripts focused solely on clinical or ophthalmic surgical fields are not suitable for submission to Experimental Eye Research and will be returned without review if received.

《Experimental Eye Research》的主要目标是发表关于眼睛及其组织实验生物学各个方面的原创研究论文，旨在揭示正常功能和疾病机制。该期刊特别欢迎涉及细胞生物学、发育生物学、遗传学、分子生物学、生理学、生物化学、生物物理学、免疫学和微生物学等学科的眼组织研究。请注意，纯临床或眼科外科领域的手稿不适合提交给《Experimental Eye Research》，如果收到此类稿件，将不经审查直接退回。

Experimental Eye Research

Several lines of evidence support the existence of a renin-angiotensin system (RAS) in the retina that is separated from the blood stream by the retinal pigment epithelium (RPE). Under physiological conditions, increased activity of intraretinal RAS regulates neuronal activity of the retina but patho-physiologically participates in retinal degeneration such as hypertensive or diabetic retinopathy. Interestingly, the RPE appears to be a modulator of intraretinal RAS in response to changes in systemic RAS. As increased systemic RAS activity is associated with increased sympathetic tonus, we investigated whether systemic β-adrenergic stimulation of the RPE also modulates renin expression in the RPE. In vivo, the mouse RPE expresses the β-adrenergic receptor subtypes 1 and 2. Staining of retina sagittal sections showed tyrosine hydroxylase positive nerve endings in the choroid indicating adrenaline/noradrenaline production sites in close proximity to the RPE. Systemic infusion of isoproterenol increased renin expression in the RPE but not in the retina. This increase was sensitive to concomitant systemic application of the angiotensin-2 receptor-type-1 blocker losartan. In vitro analysis of renin gene expression using polarized porcine RPE showed that the activity of the renin promoter can be increased by cAMP stimulation (IBMX/forskolin) but was not influenced by angiotensin-2. Thus, with the identification of the β-adrenergic system we added a new regulator of the retinal RAS with relevance for retinal function and pathology. Furthermore, it appears that the RPE is not only a close interaction partner of the photoreceptors but also a regulator or retinal activity in general.

Joana Raquel Martins

Nadine Reichhart

Nobert Kociok

Julia Stindl

Renate Foeckler

Peter Lachmann

Vladimir Todorov

Hayo Castrop

Olaf Strauß

Experimental eye research

Exp Eye Res

Systemic ß adrenergic stimulation/ sympathetic nerve system stimulation influences intraocular RAS through cAMP in the RPE.

Myopia is the most common cause of a visual refractive error worldwide. Cyclic adenosine monophosphate (cAMP)-linked signaling pathways contribute to the regulation of myopia development, and increases in cAMP accumulation promote myopia progression. To pinpoint the underlying mechanisms by which cAMP modulates myopia progression, we performed scleral transcriptome sequencing analysis in form-deprived mice, a well-established model of myopia development. Form deprivation significantly inhibited the expression levels of genes in the cAMP catabolic pathway. Quantitative real-time polymerase chain reaction analysis validated that the gene expression level of phosphodiesterase 4B (PDE4B), a cAMP hydrolase, was downregulated in form-deprived mouse eyes. Under visually unobstructed conditions, loss of PDE4B function in Pde4b-knockout mice increased the myopic shift in refraction, -3.661 ± 1.071 diopters, more than that in the Pde4b-wildtype littermates (P < 0.05). This suggests that downregulation and inhibition of PDE4B gives rise to myopia. In guinea pigs, subconjunctival injection of rolipram, a selective inhibitor of PDE4, led to myopia in normal eyes, and it also enhanced form-deprivation myopia (FDM). Subconjunctival injection of dibutyryl-cyclic adenosine monophosphate, a cAMP analog, induced only a myopic shift in the normal visually unobstructed eyes, but it did not enhance FDM. As myopia developed, axial elongation occurred during scleral remodeling that was correlated with changes in collagen fibril thickness and distribution. The median collagen fibril diameter in the FDM + rolipram group, 55.09 ± 1.83 nm, was thinner than in the FDM + vehicle group, 59.33 ± 2.06 nm (P = 0.011). Thus, inhibition of PDE4 activity with rolipram thinned the collagen fibril diameter relative to the vehicle treatment in form-deprived eyes. Rolipram also inhibited increases in collagen synthesis induced by TGF-β2 in cultured human scleral fibroblasts. The current results further support a role for PDE enzymes such as PDE4B in the regulation of normal refractive development and myopia because either loss or inhibition of PDE4B function increased myopia and FDM development through declines in the scleral collagen fibril diameter.

Fuxin Zhao

Hui Zhou

Wei Chen

Chenchen Zhao

Yangyang Zheng

Yijin Tao

Miaozhen Pan

Peter S Reinach

Jiadi Zhu

Jianhong An

Runxia Lu

Jiang-Fan Chen

Huifang Tang

Changqing Zeng

Jia Qu

Xiangtian Zhou

Declines in PDE4B activity promote myopia progression through downregulation of scleral collagen expression.

Form deprivation myopia (FDM) is characterized by loss of choroidal thickness (ChT), reduced choroidal blood perfusion (ChBP), and consequently scleral hypoxia. In some tissues, changes in levels of peroxisome proliferator-activated receptor γ (PPARγ) expression modulate hypoxia-induced pathological responses. We determined if PPARγ modulates FDM through changes in ChT, ChBP, scleral hypoxia-inducible transcription factor (HIF-1α) that in turn regulate scleral collagen type 1 (COL1) expression levels in guinea pigs. Myopia was induced by occluding one eye, while the fellow eye served as control. They received daily peribulbar injections of either the PPARγ antagonist GW9662, or the GW1929 agonist, with or without ocular occlusion for 4 weeks. Ocular refraction and biometric parameters were estimated at baseline, 2 and 4 weeks post-treatment. ChT and ChBP were measured at the 2- and 4-week time points. Western blot analysis determined the expression levels of scleral HIF-1α and COL1. GW9662 induced a myopic shift in unoccluded eyes. Conversely, GW1929 inhibited FDM progression without affecting the refraction in unoccluded eyes. GW9662 reduced both ChT and ChBP in unoccluded eyes, while GW1929 inhibited their declines in occluded eyes. Scleral HIF-1α expression rose in GW9662-treated unoccluded eyes whereas GW1929 reduced HIF-1α upregulation in occluded eyes. GW9662 downregulated scleral COL1 expression in unoccluded eyes, while GW1929 reduced their decreases in occluded eyes. Therefore, PPARγ modulates collagen expression levels and FDM through an inverse relationship between changes in PPARγ and HIF-1α expression levels.

Zhenqi Guan

Lin Kang

Yuqing Cao

Dengke Zhou

Nethrajeith Srinivasalu

Fei Zhao

PPARγ modulates refractive development and form deprivation myopia in Guinea pigs.

To investigate the impact of different duration of blue light exposure on ocular parameters and choroidal blood perfusion in guinea pigs with lens-induced myopia.

Xiao Wang

Yifan Sun

Kailei Wang

Shiqiao Yang

Changlin Luan

Bin Wu

Wei Zhang

Rui Hao

Effects of blue light exposure on ocular parameters and choroidal blood perfusion in Guinea pig.

Our previous research shown that tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) is elevated in the plasma extracellular vesicles and vitreous humor in diabetic retinopathy (DR). TNFAIP8 also significantly increases the viability of human retinal microvascular endothelial cells (HRMECs) and promotes cell migration and tube formation in vitro. To comprehensively explore its role in DR, we investigated the effect of TNFAIP8 on DR development using an animal model in this study. A TNFAIP8-overexpressing adeno-associated virus (AAV) vector and streptozotocin-induced mouse model was used. The AAV-TNFAIP8 vector was injected into the mice intravitreally, and the effect was evaluated. The evaluation included analysis of retinal structure and function using electroretinography, optical coherence tomography, and histological assessment. The influence of TNFAIP8 on the avascular area, retinal leukostasis, and the expression levels of inflammatory factors was also determined. TNFAIP8 significantly decreased a/b-wave amplitude and retinal thickness in diabetic mice. Histological assessment showed that TNFAIP8 aggravated pathological abnormalities with distorted organization of the retina. TNFAIP8 also significantly increased the avascular area, leukostasis, and the expression of inflammatory factors, such as TNFα, IL1β, ICAM1, and GFAP, in the retina. The results of this study support the role of TNFAIP8 in DR pathogenesis. A mechanistic understanding of TNFAIP8 may offer novel therapeutic strategies.

Fuhua Yang

Hui Zhang

Xinyue Yu

Qingqin Tao

Chuan Zhao

Jinying An

Xiaomin Zhang

Xiaorong Li

TNFAIP8 overexpression aggravates retinal pathophysiological features of diabetic retinopathy.

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.

Guodong Liu

Hui Li

Le Feng

Min Li

Peng Gao

Fang Wang

O-GlcNAcylation promotes astroglial-mesenchymal transition via the connexin43 pathway under high-glucose conditions

O-GlcNAc糖基化在高糖条件下通过连接蛋白43途径促进星形胶质细胞-间充质转化

Aparna Lakkaraju

Patricia Boya

Marie Csete

Deborah A. Ferrington

James B. Hurley

Alfredo A. Sadun

Peng Shang

Ruchi Sharma

Debasish Sinha

Marius Ueffing

Susan E. Brockerhoff

How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration

线粒体、溶酶体与其他细胞器之间的相互作用如何预防或促进干性年龄相关性黄斑变性

We investigated the mechanism of action of atropine in myopia control by examining its effect on choroidal hemodynamics. Blood flow was evaluated using indocyanine green (ICG) fluorescence and molecular variation during the development of form-deprivation myopia (FDM) and atropine treatment in guinea pigs. Guinea pigs were divided randomly into the normal control (NC), FDM, and FDM + 1% atropine (ATR) groups, and evaluated by spherical equivalent refractive error (SE) and axial length (AL). Choroidal hemodynamic parameters were measured via ICG fluorescence imaging including the maximal ICG fluorescence intensity (Imax), rising time (Trising), blood flow index (BFI), and mean transit time (MTT). Additionally, the expression in the choroid-RPE complex of choroidal vascular endothelial growth factor A (VEGFA) and HIF-1 α were assessed via Western blotting. Atropine inhibited the development of FDM, with effects of FD on both SE and AL being reduced. ICG fluorescence hemodynamic wide-field maps and time-series curves revealed that the atropine significantly accelerated choroidal blood flow, with reduced Trising and MTT, while increasing Imax, BFI and the number of lobulated choriocapillaris structures compared with the FDM group. In terms of molecular markers, atropine inhibited the effect of FDM, increasing VEGFA levels and reducing HIF-1α expression. These findings suggest that atropine improved choroidal hemodynamics and changed vascular markers, potentially contributing to its role in inhibiting the progression of myopia in the FDM model.

Danyang Che

Danlei Qiao

Lingfeng Lv

Yingjie Zhang

Yiting Cao

Fang Li

Shanbao Tong

Peng Miao

Jibo Zhou

Effects of Atropine on Choroidal Hemodynamics and VEGFA and HIF-1α Expression in Form-Deprivation Myopia Guinea Pigs

阿托品对形觉剥夺性近视豚鼠脉络膜血流动力学及VEGFA和HIF-1α表达的影响

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.

Sabrina Nau da Silva Piazza

Paula Bortoluzzi Canteiro

Natalia Dos Santos Tramontin

Giulia Strapazzon

Vanessa de Moraes Andrade

Alexandre Pastoris Muller

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

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 (<5.1kb) 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.

Rachel L Fehrman

Kristina J Chern

Kyle P Stoltz

Daniel M Lipinski

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

双载体与三载体rAAV递送在玻璃体内注射后的转导效率和耐受性：基因组编辑应用的研究

Abbreviation	Exp. Eye Res.
Journal Impact	2.96
Quartiles(Global)	OPHTHALMOLOGY(Q1)

ISSN	0014-4835, 1096-0007
h-index	146

Publication Information	Publisher: Academic Press，Publishing cycle: Monthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1961，Proportion of original research papers: 94.06%，Self Citation Rate:6.70%， Gold OA Rate: 25.74%
Average review cycle	网友分享经验：平均1.5月
Average recruitment ratio	网友分享经验：约37.5%

Experimental Eye Research

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