Lorenzo Ferro Desideri , Kentaro Kojima , Nina Eldridge , Denise C. Zysset-Burri , Marie Ørskov , Henrik Vorum , Bent Honoré , Martin S. Zinkernagel , Lasse Jørgensen Cehofski
{"title":"Integration of proteomics and artificial intelligence-driven OCT biomarker analysis in central retinal vein occlusion","authors":"Lorenzo Ferro Desideri , Kentaro Kojima , Nina Eldridge , Denise C. Zysset-Burri , Marie Ørskov , Henrik Vorum , Bent Honoré , Martin S. Zinkernagel , Lasse Jørgensen Cehofski","doi":"10.1016/j.exer.2025.110462","DOIUrl":"10.1016/j.exer.2025.110462","url":null,"abstract":"<div><div>Retinal OCT biomarker analysis by artificial intelligence (AI) has not previously been integrated with proteomics. Here, we combined the two techniques to elucidate novel molecular mechanisms in central retinal vein occlusion (CRVO). Proteomic data on aqueous humor samples from patients with treatment naïve CRVO complicated by macular edema (n = 21) and an age-matched, healthy control group (n = 20) was obtained from an existing cohort. Swept-source OCT macular scans (Topcon) from CRVO patients were analysed by AI-driven OCT software (Discovery platform, RetinAI AG, Bern Switzerland) to quantify retinal thicknesses and OCT biomarkers, including intraretinal fluid (IRF), subretinal fluid (SRF), and the outer nuclear layer thickness (ONL). Correlation analysis between protein expression and OCT biomarkers was performed. Proteins involved in complement activation and immune responses exhibited positive correlations with IRF, notably complement component C8 beta chain (r = 0.63, p = 0.0020) and Ig lambda-6 chain C region (r = 0.59, p = 0.0050). Negative correlations with IRF were identified for phosphatidylethanolamine-binding protein 1 (r = −0.66, p = 0.0010) and chordin-like protein 1 (r = −0.61, p = 0.0030). SRF was linked with insulin-like growth factor-binding protein complex acid labile subunit (r = 0.55, p = 0.010) and with extracellular superoxide dismutase (r = −0.63, p = 0.0022). Retinal layer thickness, particularly ONL and total retinal thickness, was positively associated with fibrinogen beta chain (r = 0.58, p = 0.0060) and fibronectin (r = 0.51, p = 0.019). The integration of AI and proteomics allowed for linking biological processes with specific OCT biomarkers. The combined analysis identified complement activation, immune response, oxidative stress, and extracellular matrix remodelling as likely driving forces of macular edema secondary to CRVO.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110462"},"PeriodicalIF":3.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198560","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}
Junfen Li , Yiqing Zhou , Sicheng He , Wenjing Mao , Xinbing Han , Xinyi Zhang , Yan Wang
{"title":"Inhibiting effect of LIPUS on epithelial-mesenchymal transition in lens epithelial cells","authors":"Junfen Li , Yiqing Zhou , Sicheng He , Wenjing Mao , Xinbing Han , Xinyi Zhang , Yan Wang","doi":"10.1016/j.exer.2025.110450","DOIUrl":"10.1016/j.exer.2025.110450","url":null,"abstract":"<div><div>To investigate the effect of low-intensity pulsed ultrasound (LIPUS) on epithelial-mesenchymal transition (EMT) in lens epithelial cells. EMT was induced using high glucose (HG) in SRA01/04 cells. Optimal parameters for LIPUS irradiation were determined by cell counting kit-8 assays and flow cytometry. Cell morphology was assessed by light microscopy, while cell migration ability was analyzed by a wound healing assay. Levels of specific proteins and the relationship between autophagy and the cytoskeleton were examined by immunofluorescence (IF) staining and Western blot (WB). Cytoskeletal structures were visualized by phalloidin staining and autophagosomes were quantified by transmission electron microscopy. EMT was successfully induced by HG treatment. Compared to the model group, LIPUS irradiation resulted in a change in cell morphology from spindle to oval, a significant decrease in cell migration area, and an increase in E-cadherin and LC3B/LC3A levels. In contrast, α-SMA and SQSTM1/P62 levels decreased, the number of autophagosomes increased and F-actin levels decreased in the LIPUS group. SRA01/04 cells treated with LIPUS irradiation after autophagy inhibitors 3-MA and CQ showed increased cell migration area compared to the 3-MA/CQ group; LC3B/LC3A levels decreased; SQSTM1/P62 and F-actin levels increased in the LIPUS + 3-MA/CQ group compared to 3-MA/CQ treatment alone. Colocalization of the cytoskeletal marker Arpc2 with the autophagy marker SQSTM1/P62 was also observed. After treatment with the cytoskeletal inhibitor CK666+LIPUS combination therapy, SQSTM1/P62 levels increased while LC3B/LC3A levels decreased. LIPUS inhibited HG-induced EMT by restoring autophagy, which appears to be associated with cytoskeletal remodeling.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110450"},"PeriodicalIF":3.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191697","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}
C. Felgerolle , E. Villalonga , A. Attallah , A. Menuet , S. Briault , M. Ardourel , O. Perche
{"title":"Characterization of gene recombination pattern induced by Tg(Crx-cre)1Tfur mouse strain in visual system organs","authors":"C. Felgerolle , E. Villalonga , A. Attallah , A. Menuet , S. Briault , M. Ardourel , O. Perche","doi":"10.1016/j.exer.2025.110461","DOIUrl":"10.1016/j.exer.2025.110461","url":null,"abstract":"<div><div>Retinas are more and more considered in research, as a part of the Central Nervous System (CNS) sharing the same embryonic origin as brain, and thus displays similarities to it on many aspects. Thus, deciphering retinal processes may bring information on downstream central structures of the CNS in addition to understanding retina by itself. Therefore, access to suitable <em>in vivo</em> tools to create appropriate models to decipher retina-specific phenomena and their impacts on other tissues became a need. Some years ago, the new murine strain Tg(Crx-cre)1Tfur was published as a tool to induce retina-specific gene recombination, and literature reported its efficiency to induce a global gene recombination in all retinal layers and cell types at post-natal ages. However, to our knowledge, no study of the retina-specificity of Tg(<em>Crx-Cre</em>)-induced recombination had been published yet. Here we aimed to further investigate the gene-recombination pattern induced by Tg(<em>Crx-Cre</em>) among the structures of the visual system, to bring clear clues of the fair use that could be done of the Tg(<em>Crx-Cre</em>) murine strain. Our results showed that Tg(<em>Crx-Cre</em>) induced a total gene recombination in retinas but also scattered significantly brain structures. Therefore we advise that Tg(Crx-cre)1Tfur must be used in studies focusing strictly on retina and conclusions should be carefully drawn taking into account the non-retina-specificity of gene recombination.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110461"},"PeriodicalIF":3.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191696","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}
Hao Mou , Haicheng She , Chang-Jun Zhang , Min Li , Wen Wang , Shu-Ning Sun , Xiao Zhang , Zi-Bing Jin
{"title":"Cathepsin H deficiency leads to myopic phenotype in mice","authors":"Hao Mou , Haicheng She , Chang-Jun Zhang , Min Li , Wen Wang , Shu-Ning Sun , Xiao Zhang , Zi-Bing Jin","doi":"10.1016/j.exer.2025.110447","DOIUrl":"10.1016/j.exer.2025.110447","url":null,"abstract":"<div><div>Genetic predisposition has been increasingly reported in patients with high myopia. A previous study reported that a deleterious mutation in cathepsin H (<em>CTSH</em>) gene causes high myopia. However, the phenotypic and mechanistic characteristics of <em>Ctsh</em>-deficient mice remain unknown. In this study, we generated a <em>Ctsh</em> knockout mouse model using CRISPR/Cas9, and confirmed the abolishment of <em>Ctsh</em> by Sanger sequencing. In the mouse model, myopic shift was measured by photorefraction and axial elongation was detected by magnetic resonance imaging (MRI). Retinal function detected by electroretinogram (ERG) indicated the scotopic responses of knockout mice were reduced, and slight retinal thinning was observed using optical coherence tomography (OCT). In addition, ribonucleic acid sequencing (RNA-seq) and real-time polymerase chain reaction (RT-PCR) demonstrated gene expression changes in the retinas of knockout mice. Our results indicated that <em>Ctsh</em> plays an important role in emmetropization and that its loss-of-function leads to myopia development.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110447"},"PeriodicalIF":3.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186878","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}
Nolan McKibben , Yanqi Zhang , Shenglin Li , Lingyan Kong , Libo Tan
{"title":"Smartphone-based fundus imaging and computer vision analysis for monitoring retinopathy of prematurity in neonatal rats with and without lutein treatment","authors":"Nolan McKibben , Yanqi Zhang , Shenglin Li , Lingyan Kong , Libo Tan","doi":"10.1016/j.exer.2025.110460","DOIUrl":"10.1016/j.exer.2025.110460","url":null,"abstract":"<div><div>Retinopathy of prematurity (ROP), caused by oxidative stress leading to abnormal retinal vessel growth, is often studied in rodent models. However, current methods rely on <em>in vitro</em> analysis, preventing the monitoring of disease progression. Fundus imaging is commonly used in clinical ophthalmology and could provide a method for <em>in vivo</em> imaging in rodents with ROP. Recently, a smartphone and condensing lens have been shown to be effective in humans and mice. The aim of this study was to develop a smartphone-based fundus camera system that can be used to monitor <em>in vivo</em> changes caused by ROP and determine its effectiveness upon introducing an intervention of lutein. KRN 633 was used to induce ROP and fundus imaging was conducted using a condensing lens and a smartphone. <em>In vitro</em> analysis of the retina was conducted for comparison using immunohistochemistry. The tortuosity was analyzed from fundus images manually using ImageJ and by a newly developed computer vision-based method. ROP induced tortuous arteries, which was improved by the administration of lutein in the fundus and microscopy images of the retina. The two imaging techniques showed a strong positive correlation. Similarly, the computer vision-based tortuosity analysis displayed a strong linear relationship with ImageJ analysis. This smartphone-based fundus camera system offers a cheap and accessible method for <em>in vivo</em> imaging to supplement traditional histological analysis. With future development, the image processing technique described can be enhanced to include other measures of visual function.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110460"},"PeriodicalIF":3.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186879","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}
Pooja Nambiar , Aasef G. Shaikh , Palak Gupta , Jordan Murray , Fatema F. Ghasia
{"title":"Binocular dysfunction in Parkinson's Disease: Decoding near triad dynamics and divergence deficits","authors":"Pooja Nambiar , Aasef G. Shaikh , Palak Gupta , Jordan Murray , Fatema F. Ghasia","doi":"10.1016/j.exer.2025.110458","DOIUrl":"10.1016/j.exer.2025.110458","url":null,"abstract":"<div><div>Parkinson's Disease (PD) is a progressive neurodegenerative disorder that often affects the oculomotor system, causing strabismus and vergence impairments, particularly convergence insufficiency when focusing on nearby objects. This study evaluated eye deviation, vergence, accommodation, and pupil responses in PD during converging and diverging gaze shifts, correlating these findings with neurologic severity using the Unified Parkinson's Disease Rating Scale (UPDRS). We recruited 19 participants with varying severity of PD and 10 age-matched controls. 26 % of PD participants (PD Group 1) exhibited disparity-driven convergence and divergence responses comparable to controls, with expected miosis during convergence and mydriasis during divergence. In contrast, 74 % of PD participants (PD Group 2) showed reduced disparity-driven convergence and divergence, with diminished miosis during convergence and mydriasis during divergence. 37 % of PD participants exhibited increased exodeviation at near (30 cm) during binocular viewing in addition to reduced disparity-driven convergence. Blur-driven vergence was more significantly reduced than disparity-driven vergence in both PD participants and controls, likely due to presbyopia. Accommodation, assessed through changes in refractive error during disparity-driven and blur-driven vergence movements, was comparable between controls and PD patients. Our study indicates that PD disrupts disparity-driven convergence and divergence while sparing accommodation and blur-driven vergence. These findings offer insight into the pathophysiology of binocular dysfunction in PD, highlighting the involvement of neural structures such as the deep cerebellar nuclei and the supra-oculomotor area in vergence deficits and strabismus. Future studies can use these metrics to evaluate the effectiveness of targeted neuromodulation therapies in alleviating binocular dysfunction in PD.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110458"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178477","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}
Jie Xu , Changkai Jia , Qiaocheng Qiu , Yuzhen Qin , Yuting Wang , Sijin Wu , Wei Li , Shengwei Ren , Yiqiang Wang
{"title":"NLRP3 proteins translocation into nuclei mediates SV40 T-antigen-induced corneal epithelial cell immortalization","authors":"Jie Xu , Changkai Jia , Qiaocheng Qiu , Yuzhen Qin , Yuting Wang , Sijin Wu , Wei Li , Shengwei Ren , Yiqiang Wang","doi":"10.1016/j.exer.2025.110455","DOIUrl":"10.1016/j.exer.2025.110455","url":null,"abstract":"<div><div>NLRP3 proteins mainly act as inflammasome core components in cytosol, but was sparsely recorded to translocate into nuclei in some conditions, such as in human simplex virus (HSV)-infected corneas, in SV40 T-Ag-immortalized human corneal epithelial cell (HCEC) line, or during differentiation of naïve T cells. This study was designed to define whether or how SV40 T-Ag transfection <em>per se</em> caused NLRP3 translocation. It was demonstrated that infection of primary human corneal epithelial cells with lentivirus coding for SV40 T-Ag induced NLRP3 proteins' translocation into nuclei. Pull-down of NLRP3-containing complexes in HCEC nuclear proteins followed by mass spectrometry revealed 285 nuclear proteins interacting with NLRP3 proteins. Clustering analysis of these proteins showed that “RNA binding”, “Nucleocytoplasmic transport” and “Viral carcinogenic pathway” were among the enriched molecular function terms or KEGG pathways. Structural modeling showed significant but differential affinities between NLRP3 proteins and histone subunits. Systemic Evolution of Ligands by EXponential enrichment (SELEX) was utilized to define DNA motifs potentially bound by NLRP3 proteins <em>in vitro</em>, and in-depth analysis of SELEXed motifs confirmed that the genes harboring those motifs were significantly associated with transcription and RNA processing. This study demonstrated that during the process of SV40 T-Ag-mediated corneal cell immortalization, NLRP3 proteins translocated into nuclei and behaved like a transcription factor. Besides confirming NLRP3 proteins’ novel functions in non-immune cells or tissues like cornea, these findings also shed light on the mechanisms of virus-mediated immortalization or viral induced carcinogenesis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110455"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181248","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}
Chen Pengjie, Sun Yiming, Wu Han, Miao Qi, Xu Mingyu, Wang Jiawei, Xu Peifang, Ye Juan
{"title":"Multi-omics analysis reveals lipid metabolism profiles and regulatory networks in meibomian glands aging","authors":"Chen Pengjie, Sun Yiming, Wu Han, Miao Qi, Xu Mingyu, Wang Jiawei, Xu Peifang, Ye Juan","doi":"10.1016/j.exer.2025.110457","DOIUrl":"10.1016/j.exer.2025.110457","url":null,"abstract":"<div><div>Aging is a significant risk factor for ocular surface diseases like meibomian gland dysfunction (MGD), which compromises tear film stability, leading to discomforts, visual impairment, and ocular structural damage. This study aims to elucidate the age-related changes in lipid metabolism and the regulation networks, providing insights into early pathogenic mechanisms and identifying potential molecular targets for preventing age-driven pathology in the MGs. We analyzed MGs from young (2 months) and aged (12 months) C57BL/6 mice using a multi-omics approach, transcriptomic analysis and lipidomic analysis. Our findings revealed shifts in lipid composition in aged MGs, especially with reduced phospholipid levels and elevated triglyceride (TG) levels. Differentially expressed genes (DEGs) in lipid metabolism were also identified, including glycerolipid, glycerophospholipid, and sphingolipid metabolism, forming a complex regulatory network of lipid metabolism. Some critical DEGs were validated by qPCR, confirming the upregulation of Akr1b8 (glycerolipid metabolism) and the downregulation of Mboat2 (glycerophospholipid metabolism), Degs2, and Sptlc3 (sphingolipid metabolism) in aged MGs. These findings highlighted lipid metabolism dysregulation as a key factor in age-related MGD, offering potential targets for future research to mitigate this condition and preserve ocular health.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110457"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180100","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}
{"title":"Breaking barriers in ocular drug delivery for Uveitis: Advanced drug delivery systems, challenges and future prospects","authors":"Anju Ambekar, Jagannath Sahoo, Kavita Singh","doi":"10.1016/j.exer.2025.110456","DOIUrl":"10.1016/j.exer.2025.110456","url":null,"abstract":"<div><div>Uveitis is inflammation of the uvea, the middle layer of the eye which comprises of iris, ciliary body and choroid. Complications associated with uveitis include chronic pain, vision impairment and even blindness if not treated adequately. Conventional treatments for uveitis include immunosuppressive medications such as corticosteroids and biologics, which present challenges of low bioavailability due to complex anatomical structure of eye, rapid drug elimination, enzymatic degradation and the blood-retinal barrier. Consequently, they require frequent administration and are often associated with systemic side effects. In comparison to conventional drug delivery advanced drug delivery systems offer advantages such as targeted drug delivery, sustained drug release and reduction in side effects. A thorough literature search was conducted using Google Scholar, PubMed, covering publications from 2000 to 2024. The search terms included “uveitis,” “pathology and pathophysiology of uveitis,” “barriers in ocular drug delivery,” and “uveitis conventional treatments.” To refine the search results, “uveitis” was combined with different keywords such as “polymeric nanoparticles,” “liposomes,” “nanomicelles,” “dendrimers,” “nanoemulsions,” “hydrogels,” “implants,” or “microneedles” to gather information related to each novel drug delivery system. Only English language studies were considered. The inclusion criteria encompassed both review and research articles specifically related to uveitis, with a focus on studies evaluating novel drug delivery systems for its treatment. Studies on ocular drug delivery systems unrelated to uveitis were excluded. No formal statistical analysis was conducted. This review highlights various advanced drug delivery approaches including polymeric nanoparticles, liposomes, nanomicelles, dendrimers, nanoemulsions, hydrogels, implants and microneedles for the treatment of uveitis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"257 ","pages":"Article 110456"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166806","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}