Experimental eye research最新文献

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Lysophosphatidic acid receptor 3 (LPAR3) regulates ocular surface chloride transport via calcium signaling
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-18 DOI: 10.1016/j.exer.2025.110346
Ethan S. Lindgren , Rongshan Yan , Yien-Ming Kuo , Qi Gao , Livia de Souza Goncalves , Feeling Y. Chen , Matilda F. Chan , Alan S. Verkman , Onur Cil , Neel D. Pasricha
{"title":"Lysophosphatidic acid receptor 3 (LPAR3) regulates ocular surface chloride transport via calcium signaling","authors":"Ethan S. Lindgren ,&nbsp;Rongshan Yan ,&nbsp;Yien-Ming Kuo ,&nbsp;Qi Gao ,&nbsp;Livia de Souza Goncalves ,&nbsp;Feeling Y. Chen ,&nbsp;Matilda F. Chan ,&nbsp;Alan S. Verkman ,&nbsp;Onur Cil ,&nbsp;Neel D. Pasricha","doi":"10.1016/j.exer.2025.110346","DOIUrl":"10.1016/j.exer.2025.110346","url":null,"abstract":"<div><div>Dry eye is a multifactorial disease associated with impaired tear film homeostasis, damaging the ocular surface epithelium. Lysophosphatidic acid receptors (LPARs) are G-protein coupled receptors involved in Ca<sup>2+</sup> and cAMP signaling via PLC and adenylyl cyclase activation. LPAR activation is involved in cell proliferation and wound healing in human corneal epithelial cells (HCECs) and in neuropathic pain. This study investigates the expression and functions of LPARs in ocular surface epithelial cells. Functional measurements of ocular surface potential difference (OSPD) were done in mice with topically applied, selective LPAR modulators. LPAR3 immunostaining was performed in mouse and human cornea and conjunctiva, and mouse lacrimal gland. LPAR-induced Ca<sup>2+</sup> signaling was studied in primary and immortalized HCECs. The general LPAR agonist, linoleoyl LPA, and the LPAR3 selective agonist, 2S-OMPT, stimulated ocular surface Cl<sup>−</sup> secretion via Ca<sup>2+</sup>-activated Cl<sup>−</sup> channels (CaCCs). LPAR3 was expressed in the corneal and conjunctival epithelia of mice and humans, as well as in mouse lacrimal gland. Activation of LPAR and LPAR3 in HCECs transiently elevated intracellular Ca<sup>2+</sup> through the G<em>q</em>/PLC signaling pathway. LPAR3 agonists may potentially have therapeutic efficacy in ocular surface diseases, including dry eye disease.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110346"},"PeriodicalIF":3.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Breaking Bruch's: How changes in Bruch's membrane influence retinal homeostasis
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-17 DOI: 10.1016/j.exer.2025.110343
Simon J. Clark , Christine Curcio , Andrew D. Dick , Sarah Doyle , Malia Edwards , Miguel Flores-Bellver , Daniel Hass , Rachel Lennon , Christopher B Toomey , Bärbel Rohrer
{"title":"Breaking Bruch's: How changes in Bruch's membrane influence retinal homeostasis","authors":"Simon J. Clark ,&nbsp;Christine Curcio ,&nbsp;Andrew D. Dick ,&nbsp;Sarah Doyle ,&nbsp;Malia Edwards ,&nbsp;Miguel Flores-Bellver ,&nbsp;Daniel Hass ,&nbsp;Rachel Lennon ,&nbsp;Christopher B Toomey ,&nbsp;Bärbel Rohrer","doi":"10.1016/j.exer.2025.110343","DOIUrl":"10.1016/j.exer.2025.110343","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110343"},"PeriodicalIF":3.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oroxylin A alleviates pyroptosis and apoptosis in human corneal epithelial cells under hyperosmotic stress by activating the SIRT3-SOD2/HIF-1α pathway
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-15 DOI: 10.1016/j.exer.2025.110345
Xueqing Liu , Qiang Xu , Nan Jiang, Wendan Zheng, Ziteng Yuan, Liting Hu
{"title":"Oroxylin A alleviates pyroptosis and apoptosis in human corneal epithelial cells under hyperosmotic stress by activating the SIRT3-SOD2/HIF-1α pathway","authors":"Xueqing Liu ,&nbsp;Qiang Xu ,&nbsp;Nan Jiang,&nbsp;Wendan Zheng,&nbsp;Ziteng Yuan,&nbsp;Liting Hu","doi":"10.1016/j.exer.2025.110345","DOIUrl":"10.1016/j.exer.2025.110345","url":null,"abstract":"<div><div>Dry eye disease (DED) is a common ocular surface problem. Ocular surface inflammation and oxidative stress triggered by increased tear osmolarity are crucial pathogeneses of DED. Oroxylin A (OA) extracted from Scutellaria baicalensis exhibits anti-inflammatory, antioxidant, and cell protective properties. The aim of this study was to determine the protective effect and explore the potential mechanisms of OA on hyperosmotic stress-induced human corneal epithelial cells (HCECs). In this study, we demonstrated that OA exhibited a marked protective effect on hyperosmolarity-induced HCEC damage, including improving cell viability and decreasing lactate dehydrogenase release. Furthermore, OA reduced the expression of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and the generation of oxidative stress-related markers (ROS and NO) in hyperosmotic stress-induced HCECs. In addition, OA decreased HCEC pyroptosis by decreasing NLRP3, caspase-1, cleaved-caspase-1, and N-GSDMD levels. OA also decreased HCEC apoptosis by enhancing Bcl-2 expression while simultaneously decreasing caspase-3 and Bax levels. Moreover, OA enhanced SIRT3 expression in hyperosmotic stress-induced HCECs. A SIRT3 inhibitor reversed the alleviation of pyroptosis and apoptosis induced by OA. SIRT3 could promote SOD2 expression and inhibit HIF-1α and ROS expression in hyperosmotic stress-induced HCECs. In conclusion, OA exhibits anti-inflammatory and antioxidant properties and can alleviate the pyroptosis and apoptosis of HCECs under hyperosmotic stimulation by activating the SIRT3-SOD2/HIF-1α signaling pathway. Therefore, OA may be a new treatment target for dry eye disease.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110345"},"PeriodicalIF":3.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647655","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
Retinal imaging in an era of open science and privacy protection
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-14 DOI: 10.1016/j.exer.2025.110341
Nayoon Gim , Marian Blazes , Clara I. Sánchez , Luca Zalunardo , Giulia Corradetti , Tobias Elze , Naoto Honda , Nadia K. Waheed , Anne Marie Cairns , M. Valeria Canto-Soler , Amitha Domalpally , Mary Durbin , Daniela Ferrara , Jewel Hu , Prashant Nair , Srinivas R. Sadda , Tiarnan D.L. Keenan , Cecilia S. Lee , the RIMR Consortium
{"title":"Retinal imaging in an era of open science and privacy protection","authors":"Nayoon Gim ,&nbsp;Marian Blazes ,&nbsp;Clara I. Sánchez ,&nbsp;Luca Zalunardo ,&nbsp;Giulia Corradetti ,&nbsp;Tobias Elze ,&nbsp;Naoto Honda ,&nbsp;Nadia K. Waheed ,&nbsp;Anne Marie Cairns ,&nbsp;M. Valeria Canto-Soler ,&nbsp;Amitha Domalpally ,&nbsp;Mary Durbin ,&nbsp;Daniela Ferrara ,&nbsp;Jewel Hu ,&nbsp;Prashant Nair ,&nbsp;Srinivas R. Sadda ,&nbsp;Tiarnan D.L. Keenan ,&nbsp;Cecilia S. Lee ,&nbsp;the RIMR Consortium","doi":"10.1016/j.exer.2025.110341","DOIUrl":"10.1016/j.exer.2025.110341","url":null,"abstract":"<div><div>Artificial intelligence (AI) holds great promise for analyzing complex data to advance patient care and disease research. For example, AI interpretation of retinal imaging may enable the development of noninvasive retinal biomarkers of systemic disease. One potential limitation, however, is government regulation regarding retinal imaging as biometric data, which has been recently under debate in the United States. Although careful regard for patient privacy is key to maintaining trust in the widespread use of AI in healthcare, the designation of retinal imaging as biometric data would greatly restrict retinal biomarker research. There are several reasons why retinal imaging should not be considered biometric data. Unlike images of the iris, high quality images of the retina are more difficult to obtain, requiring specialized training and equipment, and often requiring pupil dilation for optimal quality. In addition, retinal imaging features can vary over time with changes in health status, and retinal images are not currently linked to any large identification databases. While the protection of patient privacy is imperative, there is also a need for large retinal imaging datasets to advance AI research. Given the limitations of retinal imaging as a source of biometric data, the research community should work to advocate for the continued use of retinal imaging in AI research.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110341"},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Brain activation following flexible stimulation paradigms of transcorneal electrical stimulation (TES) in a murine model of glaucoma
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-14 DOI: 10.1016/j.exer.2025.110326
D. Gomez-Maldonado , R. Shovmer , D.M. Inman , R.K. Willits
{"title":"Brain activation following flexible stimulation paradigms of transcorneal electrical stimulation (TES) in a murine model of glaucoma","authors":"D. Gomez-Maldonado ,&nbsp;R. Shovmer ,&nbsp;D.M. Inman ,&nbsp;R.K. Willits","doi":"10.1016/j.exer.2025.110326","DOIUrl":"10.1016/j.exer.2025.110326","url":null,"abstract":"<div><div>Transcorneal electrical stimulation (TES) has been shown as a promising treatment for optic neuropathy in DBA/2J glaucoma model mice, however the current knowledge about the most effective application parameters, such as intensity and duration, is limited. In this study, after electrophysiological evaluation and intraocular pressure measurements, a single TES treatment in both eyes was performed and expression of c-Fos in the superior colliculus measured as a response. Groups were formed with 4, 8-month-old mice, 2 male and 2 female, and treated with 1, 10, or 100 μA for 10 or 30 min; a group with no stimulation was used as negative control, and as positive control, a group of mice were injected intraperitoneally with saline solution. As pathophysiology baseline, groups of 3-month-old mice were used to compare the c-Fos expression after injection (positive control), and with no stimulation (negative controls). The 8-month-old mice presented measurable progression of neuropathy compared to young controls. Active c-Fos-labeled cells were detected with TES application as low as 1 μA for 30 min, suggesting that benefits of TES can be harnessed with flexible application paradigms.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110326"},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Designing the next generation of clinical trials in intermediate AMD-a consensus driven, pragmatic, proof of concept early intervention study
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-14 DOI: 10.1016/j.exer.2025.110340
Robyn H. Guymer , Philip J. Rosenfeld , Justis P. Ehlers , Mayssa Attar , Hao Chen , Frederick Ferris , James G. Fujimoto , Michael Ip , Maximilian Pfau , Marlene Saßmannshausen , Jie Shen , David N. Zacks , Tavé van Zyl , Zhichao Wu , Glenn J. Jaffe
{"title":"Designing the next generation of clinical trials in intermediate AMD-a consensus driven, pragmatic, proof of concept early intervention study","authors":"Robyn H. Guymer ,&nbsp;Philip J. Rosenfeld ,&nbsp;Justis P. Ehlers ,&nbsp;Mayssa Attar ,&nbsp;Hao Chen ,&nbsp;Frederick Ferris ,&nbsp;James G. Fujimoto ,&nbsp;Michael Ip ,&nbsp;Maximilian Pfau ,&nbsp;Marlene Saßmannshausen ,&nbsp;Jie Shen ,&nbsp;David N. Zacks ,&nbsp;Tavé van Zyl ,&nbsp;Zhichao Wu ,&nbsp;Glenn J. Jaffe","doi":"10.1016/j.exer.2025.110340","DOIUrl":"10.1016/j.exer.2025.110340","url":null,"abstract":"<div><div>A greater understanding of the pathophysiology of AMD has yielded potential therapeutic strategies for slowing vision loss. Structural imaging biomarkers and novel functional outcomes, both under intensive study as surrogate endpoints in AMD clinical trials, are new granular tools needed to assess disease progression and follow response to therapy. These advances have created, for the first time, the possibility to intervene early in AMD, and to measure success in a time frame feasible for clinical trials. At the 2024 Ryan Initiative for Macular Research (RIMR) meeting, a consensus was reached for design of a hypothetical, pragmatic, proof of concept, 24-month, early intervention study to determine the efficacy of an intervention in subjects with intermediate AMD (iAMD). Although further research is needed, using natural history cohorts and intervention trials to validate the proposed trial design and endpoints, this paper presents an AMD expert consensus framework for early AMD clinical trials, that we hope will also be useful for therapeutic developers and regulators. Viable clinical trial strategies are needed to develop treatments that slow the progression of AMD prior to the development of vision-threatening late AMD; this consensus document should aid in reaching this goal.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110340"},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective effects and mechanisms of lactoferrin and HIF-1α on dry eye syndrome in mice 乳铁蛋白和 HIF-1α 对小鼠干眼症的保护作用和机制
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-13 DOI: 10.1016/j.exer.2025.110339
Shanshan Sun, Wang Zong, Lei Jiang, Juan Chen, De Wu, Zhuo Sun
{"title":"Protective effects and mechanisms of lactoferrin and HIF-1α on dry eye syndrome in mice","authors":"Shanshan Sun,&nbsp;Wang Zong,&nbsp;Lei Jiang,&nbsp;Juan Chen,&nbsp;De Wu,&nbsp;Zhuo Sun","doi":"10.1016/j.exer.2025.110339","DOIUrl":"10.1016/j.exer.2025.110339","url":null,"abstract":"<div><div>The objective of this study was to investigate the protective effects and related mechanisms of lactoferrin and HIF-1α on dry eye syndrome (DED) in mice. The expression levels of lactoferrin and HIF-1α in tears of DED patients and normal controls were detected. A DED mouse model received lactoferrin (50 mg/kg dissolved in 2 mL PBS) or DMOG (40 mg/kg dissolved in 2 mL PBS) orally daily for 28 days. DMOG (dimethyloxaloylglycine) is a hypoxia-inducible factor prolyl hydroxylase inhibitor. Various tests conducted in this study were phenol red thread test, corneal fluorescein sodium staining, hematoxylin-eosin (HE) staining, PAS staining of conjunctiva, TUNEL staining, and Western blotting. Compared to normal controls, DED patients showed significantly decreased expression of lactoferrin and increased expression of HIF-1α in tears (P &lt; 0.05). Compared to normal mice, DED model mice exhibited significantly decreased tear secretion, goblet cell count, Bcl-2, lactoferrin, and STAT3 protein expression levels, and significantly increased corneal fluorescein sodium staining grade, TUNEL positivity rate, Bax, HIF-1α, p21, and p27 protein expression levels (P &lt; 0.05). Treatment with lactoferrin or DMOG significantly increased tear secretion, goblet cell count, Bcl-2, lactoferrin, HIF-1α, and STAT3 protein expression levels, and significantly decreased corneal fluorescein sodium staining grade, TUNEL positivity rate, Bax, p21, and p27 protein expression levels in DED model mice (P &lt; 0.05). Normal mice showed normal corneal morphology. Compared to normal mice, DED model mice exhibited rough surface of corneal epithelial cell layer with vacuolated cells and inflammatory cell infiltration. Treatment with lactoferrin or DMOG significantly alleviated corneal lesions in DED model mice. Lactoferrin and HIF-1α exert protective effects on DED in mice.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110339"},"PeriodicalIF":3.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633547","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
Publicly available imaging datasets for age-related macular degeneration: Evaluation according to the Findable, Accessible, Interoperable, Reusable (FAIR) principles
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-13 DOI: 10.1016/j.exer.2025.110342
Nayoon Gim , Alina Ferguson , Marian Blazes , Sanjay Soundarajan , Aydan Gasimova , Yu Jiang , Clara I. Sánchez , Luca Zalunardo , Giulia Corradetti , Tobias Elze , Naoto Honda , Nadia K. Waheed , Anne Marie Cairns , M. Valeria Canto-Soler , Amitha Domalpally , Mary Durbin , Daniela Ferrara , Jewel Hu , Prashant Nair , Aaron Y. Lee , Cecilia S. Lee
{"title":"Publicly available imaging datasets for age-related macular degeneration: Evaluation according to the Findable, Accessible, Interoperable, Reusable (FAIR) principles","authors":"Nayoon Gim ,&nbsp;Alina Ferguson ,&nbsp;Marian Blazes ,&nbsp;Sanjay Soundarajan ,&nbsp;Aydan Gasimova ,&nbsp;Yu Jiang ,&nbsp;Clara I. Sánchez ,&nbsp;Luca Zalunardo ,&nbsp;Giulia Corradetti ,&nbsp;Tobias Elze ,&nbsp;Naoto Honda ,&nbsp;Nadia K. Waheed ,&nbsp;Anne Marie Cairns ,&nbsp;M. Valeria Canto-Soler ,&nbsp;Amitha Domalpally ,&nbsp;Mary Durbin ,&nbsp;Daniela Ferrara ,&nbsp;Jewel Hu ,&nbsp;Prashant Nair ,&nbsp;Aaron Y. Lee ,&nbsp;Cecilia S. Lee","doi":"10.1016/j.exer.2025.110342","DOIUrl":"10.1016/j.exer.2025.110342","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD), a leading cause of vision loss among older adults, affecting more than 200 million people worldwide. With no cure currently available and a rapidly increasing prevalence, emerging approaches such as artificial intelligence (AI) and machine learning (ML) hold promise for advancing the study of AMD. The effective utilization of AI and ML in AMD research is highly dependent on access to high-quality and reusable clinical data. The Findable, Accessible, Interoperable, Reusable (FAIR) principles, published in 2016, provide a framework for sharing data that is easily useable by both humans and machines. However, it is unclear how these principles are implemented with regards to ophthalmic imaging datasets for AMD research. We evaluated openly available AMD-related datasets containing optical coherence tomography (OCT) data against the FAIR principles. The assessment revealed that none of the datasets were fully compliant with FAIR principles. Specifically, compliance rates were 5 % for Findable, 82 % for Accessible, 73 % for Interoperable, and 0 % for Reusable. The low compliance rates can be attributed to the relatively recent emergence of these principles and the lack of established standards for data and metadata formatting in the AMD research community. This article presents our findings and offers guidelines for adopting FAIR practices to enhance data sharing in AMD research.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110342"},"PeriodicalIF":3.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633460","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 therapeutic effect and mechanism of carnosic acid in Aspergillus fumigatus keratitis
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-13 DOI: 10.1016/j.exer.2025.110338
Menghui Chi, Lingwen Gu, Lina Zhang, Jing Lin, Qian Wang, Xueyun Fu, Xue Tian, Ziyi Wang, Bing Yu, Wenyao Liu, Cui Li, Guiqiu Zhao
{"title":"The therapeutic effect and mechanism of carnosic acid in Aspergillus fumigatus keratitis","authors":"Menghui Chi,&nbsp;Lingwen Gu,&nbsp;Lina Zhang,&nbsp;Jing Lin,&nbsp;Qian Wang,&nbsp;Xueyun Fu,&nbsp;Xue Tian,&nbsp;Ziyi Wang,&nbsp;Bing Yu,&nbsp;Wenyao Liu,&nbsp;Cui Li,&nbsp;Guiqiu Zhao","doi":"10.1016/j.exer.2025.110338","DOIUrl":"10.1016/j.exer.2025.110338","url":null,"abstract":"<div><div>Fungal keratitis is a vision-threatening corneal infectious disease. However, clinically therapeutic medicines cannot attain ideal efficacy due to limited control of fungal virulence and excessive inflammatory response. Carnosic acid (CA) is a phenolic diterpene, which has been reported to have multiple abilities including antibacterial, anti-inflammatory and antioxidant. The therapeutic efficacy and potential mechanism of CA in fungal keratitis remain unknown. This study aimed to confirm the therapeutic role and potential mechanism of CA in <em>Aspergillus fumigatus</em> (<em>A. fumigatus</em>)–caused keratitis. In this study, we demonstrated that CA markedly suppressed the growth of <em>A. fumigatus</em> hyphae, the generation of biofilms and the integrity of the hyphal membrane. <em>A. fumigatus-</em>related genes (RodA, RodB, FKs, Rho1, CshA-C and Cyp51A-B) levels were suppressed under CA treatment. CA at 5 μg/mL and 10 μg/mL obviously promoted cell proliferation. In <em>A. fumigatus-</em>infected mice cornea, CA relieved the severity of corneal impairment, inhibited neutrophil recruitment and fungal load. Compared with inactivated hyphae, CA down-regulated the mRNA and protein levels of inflammatory cytokines, Dectin-1, NLRP3, cleaved caspase-1, IL-18 and IL-1β. Moreover, Curdlan (a specific agonist of Dectin-1) stimulation could promote the expression of NLRP3, cleaved caspase-1, IL-18 and IL-1β, which could be down-regulated by CA treatment. In conclusion, CA displays antifungal function on <em>A. fumigatus</em>. CA ameliorates the prognosis of keratomycosis by suppressing inflammatory cytokines production, which is regulated by Dectin-1 and pyroptosis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110338"},"PeriodicalIF":3.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629319","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
Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms
IF 3 2区 医学
Experimental eye research Pub Date : 2025-03-13 DOI: 10.1016/j.exer.2025.110344
Rinki Ratnapriya , Felix Grassman , Rui Chen , Alex Hewitt , Jianhai Du , Daniel R. Saban , Caroline C.W. Klaver , John Ash , Dwight Stambolian , Santa J. Tumminia , Jiang Qian , Deeba Husain , Sudha K. Iyengar , Anneke I. den Hollander
{"title":"Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms","authors":"Rinki Ratnapriya ,&nbsp;Felix Grassman ,&nbsp;Rui Chen ,&nbsp;Alex Hewitt ,&nbsp;Jianhai Du ,&nbsp;Daniel R. Saban ,&nbsp;Caroline C.W. Klaver ,&nbsp;John Ash ,&nbsp;Dwight Stambolian ,&nbsp;Santa J. Tumminia ,&nbsp;Jiang Qian ,&nbsp;Deeba Husain ,&nbsp;Sudha K. Iyengar ,&nbsp;Anneke I. den Hollander","doi":"10.1016/j.exer.2025.110344","DOIUrl":"10.1016/j.exer.2025.110344","url":null,"abstract":"<div><div>Genome-wide association studies have been remarkably successful in identifying genetic variants associated with age-related macular degeneration (AMD), demonstrating a strong genetic component largely driven by common variants. However, progress in translating these genetic findings into a deeper understanding of disease mechanisms and new therapies has been slow. Slow progress in this area can be attributed to limited knowledge of the functional impact of AMD-associated non-coding variants on gene function, the molecular mechanisms and cell types underlying disease. This review offers a comprehensive overview of functional genomics approaches to uncover the genetic, epigenetic, cellular and molecular mechanisms underlying AMD and outlines future directions for research.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110344"},"PeriodicalIF":3.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631832","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
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