{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:32:51Z","timestamp":1763706771116,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008641","name":"Chung Shan Medical University","doi-asserted-by":"publisher","award":["CSMU-INT-102-07","MOST 110-2320-B-040-022"],"award-info":[{"award-number":["CSMU-INT-102-07","MOST 110-2320-B-040-022"]}],"id":[{"id":"10.13039\/501100008641","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["CSMU-INT-102-07","MOST 110-2320-B-040-022"],"award-info":[{"award-number":["CSMU-INT-102-07","MOST 110-2320-B-040-022"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial\u2013mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.<\/jats:p>","DOI":"10.3390\/biology13030133","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T04:04:14Z","timestamp":1708401854000},"page":"133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6332-181X","authenticated-orcid":false,"given":"Chun-Yen","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung City 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da-Fong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung City 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Jia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Sheng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung City 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8658-9703","authenticated-orcid":false,"given":"David Pei-Cheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 402, Taiwan"},{"name":"Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung City 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4570-1268","authenticated-orcid":false,"given":"Han-Hsin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung City 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4103\/ijo.IJO_646_17","article-title":"Anatomy of cornea and ocular surface","volume":"66","author":"Sridhar","year":"2018","journal-title":"Indian J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100904","DOI":"10.1016\/j.preteyeres.2020.100904","article-title":"Corneal endothelial dysfunction: Evolving understanding and treatment options","volume":"82","author":"Price","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.jcrs.2010.12.037","article-title":"Anatomy and physiology of the cornea","volume":"37","author":"DelMonte","year":"2011","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Blackburn, B.J., Jenkins, M.W., Rollins, A.M., and Dupps, W.J. (2019). A Review of Structural and Biomechanical Changes in the Cornea in Aging, Disease, and Photochemical Crosslinking. Front. Bioeng. Biotechnol., 7.","DOI":"10.3389\/fbioe.2019.00066"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1136\/bjo.81.10.814","article-title":"Aging and the cornea","volume":"81","author":"Faragher","year":"1997","journal-title":"Br. J. Ophthalmol."},{"key":"ref_6","first-page":"640","article-title":"Effect of Aging on Cornea of Male Albino Rat and the Possible Protective Role of Vitamin, C","volume":"45","author":"Yassa","year":"2020","journal-title":"Egypt. J. Histol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0047-6374(00)00227-X","article-title":"Does MMP-2 expression and secretion change with increasing serial passage of keratocytes in culture?","volume":"122","author":"Sandeman","year":"2001","journal-title":"Mech. Ageing Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1186\/s13287-020-02046-2","article-title":"Regenerative capacity of the corneal transition zone for endothelial cell therapy","volume":"11","author":"Sie","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1073\/pnas.1912546116","article-title":"Ultraviolet A light induces DNA damage and estrogen-DNA adducts in Fuchs endothelial corneal dystrophy causing females to be more affected","volume":"117","author":"Liu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.omtn.2022.01.005","article-title":"Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy","volume":"27","author":"Wang","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Stunf Pukl, S. (2022). MicroRNA of Epithelial to Mesenchymal Transition in Fuchs\u2019 Endothelial Corneal Dystrophy. Genes, 13.","DOI":"10.3390\/genes13101711"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.freeradbiomed.2020.12.445","article-title":"Cell cycle re-entry and arrest in G2\/M phase induces senescence and fibrosis in Fuchs Endothelial Corneal Dystrophy","volume":"164","author":"White","year":"2021","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cui, Z., Zeng, Q., Guo, Y., Liu, S., Wang, P., Xie, M., and Chen, J. (2018). Pathological molecular mechanism of symptomatic late-onset Fuchs endothelial corneal dystrophy by bioinformatic analysis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197750"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.1167\/iovs.08-3361","article-title":"Exfoliative epitheliopathy of bullous keratopathy with breaches in the MUC16 Glycocalyx","volume":"50","author":"Glasgow","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.21037\/atm-20-4389","article-title":"Animal models of corneal endothelial dysfunction to facilitate development of novel therapies","volume":"9","author":"Park","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1093\/gerona\/glz061","article-title":"Klotho: An Elephant in Aging Research","volume":"74","author":"Cheikhi","year":"2019","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1089\/biores.2020.0004","article-title":"Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs","volume":"9","author":"Moos","year":"2020","journal-title":"Biores. Open Access"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1080\/02713683.2016.1259421","article-title":"The Expressions of Klotho Family Genes in Human Ocular Tissues and in Anterior Lens Capsules of Age-Related Cataract","volume":"42","author":"Zhang","year":"2017","journal-title":"Curr. Eye Res."},{"key":"ref_19","first-page":"2544","article-title":"Epigenetic changes of the Klotho gene in age-related cataracts","volume":"19","author":"Jin","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e439","DOI":"10.1016\/j.jfo.2019.09.001","article-title":"Corneal topography in clinical practice","volume":"42","author":"Ghemame","year":"2019","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_21","first-page":"854","article-title":"Dietary zerumbone prevents mouse cornea from UVB-induced photokeratitis through inhibition of NF-\u03baB, iNOS, and TNF-\u03b1 expression and reduction of MDA accumulation","volume":"17","author":"Chen","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1001\/archophthalmol.2009.316","article-title":"Essential role for c-Jun N-terminal kinase 2 in corneal epithelial response to desiccating stress","volume":"127","author":"Pangelinan","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1093\/bioinformatics\/btaa847","article-title":"Colour deconvolution: Stain unmixing in histological imaging","volume":"37","author":"Landini","year":"2021","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/0471142727.mb1415s102","article-title":"Basic image analysis and manipulation in ImageJ","volume":"102","author":"Hartig","year":"2013","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.bbagen.2009.02.005","article-title":"Klotho and aging","volume":"1790","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101766","DOI":"10.1016\/j.arr.2022.101766","article-title":"Aging-suppressor Klotho: Prospects in diagnostics and therapeutics","volume":"82","author":"Abraham","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/jnc.12353","article-title":"Retinitis Pigmentosa: Over-expression of anti-ageing protein Klotho in degenerating photoreceptors","volume":"127","author":"Farinelli","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6675","DOI":"10.1167\/iovs.13-12550","article-title":"The age-regulating protein klotho is vital to sustain retinal function","volume":"54","author":"Reish","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s41419-023-05851-8","article-title":"Klotho prevents transforming growth factor-beta2-induced senescent-like morphological changes in the retinal pigment epithelium","volume":"14","author":"Jang","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/jnc.13902","article-title":"The neuroprotective effect of latanoprost acts via klotho-mediated suppression of calpain activation after optic nerve transection","volume":"140","author":"Yamamoto","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wu, C.Y., Song, D.F., Lu, T.H., Chen, Z.J., Tsai, S.M., Liu, Y.J., Chang, H.H., and Lin, D.P. (2023). Klotho Null Mutation Indirectly Leads to Age-Related Lacrimal Gland Degeneration in Mutant Mice. Biology, 12.","DOI":"10.3390\/biology12101328"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jtos.2022.06.004","article-title":"Impact of aging on the pathophysiology of dry eye disease: A systematic review and meta-analysis","volume":"25","author":"Kitazawa","year":"2022","journal-title":"Ocul. Surf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.exer.2018.01.024","article-title":"Reduced intraepithelial corneal nerve density and sensitivity accompany desiccating stress and aging in C57BL\/6 mice","volume":"169","author":"Stepp","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.ajpath.2013.11.019","article-title":"Ocular surface disease and dacryoadenitis in aging C57BL\/6 mice","volume":"184","author":"McClellan","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1167\/iovs.19-26631","article-title":"The Effects of Aging on Corneal and Ocular Surface Homeostasis in Mice","volume":"60","author":"Hill","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0002-9440(10)62232-8","article-title":"Matrix metalloproteinase-9 knockout confers resistance to corneal epithelial barrier disruption in experimental dry eye","volume":"166","author":"Pflugfelder","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.preteyeres.2004.04.002","article-title":"Collagens and collagen-related matrix components in the human and mouse eye","volume":"23","author":"Ihanamaki","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pouw, A.E., Greiner, M.A., Coussa, R.G., Jiao, C., Han, I.C., Skeie, J.M., Fingert, J.H., Mullins, R.F., and Sohn, E.H. (2021). Cell-Matrix Interactions in the Eye: From Cornea to Choroid. Cells, 10.","DOI":"10.3390\/cells10030687"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"418","DOI":"10.3892\/ol.2021.12679","article-title":"Antiaging gene Klotho regulates epithelial-mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin-2 expression","volume":"21","author":"Takegahara","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"999667","DOI":"10.3389\/fonc.2022.999667","article-title":"Synergistic effects of sodium butyrate and cisplatin against cervical carcinoma in vitro and in vivo","volume":"12","author":"Chu","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.18632\/aging.102831","article-title":"SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt\/\u03b2-catenin signaling pathway","volume":"12","author":"Tian","year":"2020","journal-title":"Aging"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1167\/iovs.19-26983","article-title":"Induction of Fibroblast Senescence During Mouse Corneal Wound Healing","volume":"60","author":"Wang","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Higuchi, A., Inoue, H., Kawakita, T., Ogishima, T., and Tsubota, K. (2012). Selenium compound protects corneal epithelium against oxidative stress. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045612"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1006\/exer.1999.0790","article-title":"Expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in inflammation-associated corneal neovascularization","volume":"70","author":"Kvanta","year":"2000","journal-title":"Exp. Eye Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.21873\/invivo.12405","article-title":"Bioluminescence Imaging of Matrix Metalloproteinases-2 and -9 Activities in Ethanol-injured Cornea of Mice","volume":"35","author":"Park","year":"2021","journal-title":"In Vivo"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1001\/jamaophthalmol.2018.2031","article-title":"Association of the Gutta-Induced Microenvironment With Corneal Endothelial Cell Behavior and Demise in Fuchs Endothelial Corneal Dystrophy","volume":"136","author":"Kocaba","year":"2018","journal-title":"JAMA Ophthalmol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.1167\/iovs.03-1145","article-title":"Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface","volume":"45","author":"Luo","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.survophthal.2015.11.006","article-title":"Matrix metalloproteinase 14 modulates signal transduction and angiogenesis in the cornea","volume":"61","author":"Chang","year":"2016","journal-title":"Surv. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1038\/s41467-020-17399-8","article-title":"Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue","volume":"11","author":"Diwanji","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.mam.2011.10.006","article-title":"Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation","volume":"32","author":"Hybertson","year":"2011","journal-title":"Mol. Aspects Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dai, Y., Zhang, J., Xiang, J., Li, Y., Wu, D., and Xu, J. (2019). Calcitriol inhibits ROS-NLRP3-IL-1\u03b2 signaling axis via activation of Nrf2-antioxidant signaling in hyperosmotic stress stimulated human corneal epithelial cells. Redox Biol., 21.","DOI":"10.1016\/j.redox.2018.101093"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/s41423-019-0296-z","article-title":"NLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodeling","volume":"18","author":"Unamuno","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Petznick, A., Madigan, M.C., Garrett, Q., Sweeney, D.F., and Evans, M.D. (2013). Contributions of ocular surface components to matrix-metalloproteinases (MMP)-2 and MMP-9 in feline tears following corneal epithelial wounding. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071948"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"100095","DOI":"10.1016\/j.medidd.2021.100095","article-title":"Roles of matrix metalloproteinases in the cornea: A special focus on macular corneal dystrophy","volume":"11","author":"Kaya","year":"2021","journal-title":"Med. Drug Discov."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Corsello, T., Komaravelli, N., and Casola, A. (2018). Role of Hydrogen Sulfide in NRF2- and Sirtuin-Dependent Maintenance of Cellular Redox Balance. Antioxidants, 7.","DOI":"10.3390\/antiox7100129"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.chemosphere.2019.04.001","article-title":"Tetracycline antibiotics as PI3K inhibitors in the Nrf2-mediated regulation of antioxidative stress in zebrafish larvae","volume":"226","author":"Yu","year":"2019","journal-title":"Chemosphere"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1161\/CIRCRESAHA.120.317348","article-title":"Klotho Deficiency Causes Heart Aging via Impairing the Nrf2-GR Pathway","volume":"128","author":"Chen","year":"2021","journal-title":"Circ. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.bbrc.2020.11.061","article-title":"Klotho ameliorates diabetic nephropathy by activating Nrf2 signaling pathway in podocytes","volume":"534","author":"Xing","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1093\/jb\/mvac014","article-title":"NRF2 pathway activation attenuates ageing-related renal phenotypes due to \u03b1-klotho deficiency","volume":"171","author":"Zhao","year":"2022","journal-title":"J. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"108862","DOI":"10.1016\/j.exer.2021.108862","article-title":"Association of macular corneal dystrophy with excessive cell senescence and apoptosis induced by the novel mutant CHST6","volume":"214","author":"Hao","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_61","first-page":"1566","article-title":"Expression of cell cycle-associated proteins in human and rabbit corneal endothelium in situ","volume":"37","author":"Joyce","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Liu, M., Wang, W., Wang, J., Fang, C., and Liu, T. (2022). Z-Guggulsterone alleviates renal fibrosis by mitigating G2\/M cycle arrest through Klotho\/p53 signaling. Chem. Biol. Interact., 354.","DOI":"10.1016\/j.cbi.2022.109846"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1016\/j.celrep.2020.01.074","article-title":"Pulsatile MAPK Signaling Modulates p53 Activity to Control Cell Fate Decisions at the G2 Checkpoint for DNA Damage","volume":"30","author":"De","year":"2020","journal-title":"Cell. Rep."},{"key":"ref_64","first-page":"455","article-title":"Behavior pattern of early-stage ocular surface squamous cell carcinoma in non-HIV patients","volume":"60","author":"Mocanu","year":"2019","journal-title":"Rom. J. Morphol. Embryol. Rev. Roum. De Morphol. Et Embryol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/3\/133\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:02:34Z","timestamp":1760104954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/3\/133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,20]]},"references-count":64,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["biology13030133"],"URL":"https:\/\/doi.org\/10.3390\/biology13030133","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2024,2,20]]}}}