{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:27:47Z","timestamp":1790458067448,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Medical Research Council, Singapore","award":["NMRC\/NIG\/0003\/2007"],"award-info":[{"award-number":["NMRC\/NIG\/0003\/2007"]}]},{"name":"National Medical Research Council, Singapore","award":["NMRC\/IRG\/1117\/2008"],"award-info":[{"award-number":["NMRC\/IRG\/1117\/2008"]}]},{"name":"National Medical Research Council, Singapore","award":["NMRC\/CG\/015\/2013"],"award-info":[{"award-number":["NMRC\/CG\/015\/2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Myopia, a prevalent refractive error disorder worldwide, is characterized by the elongation of the eye, leading to visual abnormalities. Understanding the genetic factors involved in myopia is crucial for developing therapeutic and preventive measures. Unfortunately, only a limited number of genes with well-defined functionality have been associated with myopia. In this study, we found that the homozygous TGM2-deleted gene in mice protected against the development of myopia by slowing down the elongation of the eye. The effectiveness of gene knockdown was confirmed by achieving a 60 percent reduction in TGM-2 transcript levels through the use of TGM-2-specific small interfering RNA (siRNA) in human scleral fibroblasts (SFs). Furthermore, treating normal mouse SFs with various transglutaminase inhibitors led to the down-regulation of TGM-2 expression, with the most significant reduction observed with specific TGM-2 inhibitors. Additionally, the study found that the pharmacological blockade of muscarinic receptors also slowed the progression of myopia in mice, and this effect was accompanied by a decrease in TGM-2 enzyme expression. Specifically, mice with homozygous mAChR5, mAChR1, and\/or mAChR4 and knockout mice exhibited higher levels of TGM-2 mRNA compared to mice with homozygous mAChR2 and three knockout mice (fold changes of 5.8, 2.9, 2.4, \u22122.2, and \u22124.7, respectively; p &lt; 0.05). These findings strongly suggest that both TGM-2 and muscarinic receptors play central roles in the development of myopia, and blocking these factors could potentially be useful in interfering with the progression of this condition. In conclusion, targeting TGM-2 may have a beneficial effect regarding myopia, and this may also be at least partially be the mechanism of anti-muscarinic drugs in myopia. Further studies should investigate the interaction between TGM-2 and muscarinic receptors, as well as the changes in other extracellular matrix genes associated with growth during the development of myopia.<\/jats:p>","DOI":"10.3390\/biom13071045","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"1045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular Basis of Transglutaminase-2 and Muscarinic Cholinergic Receptors in Experimental Myopia: A Target for Myopia Treatment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-9784","authenticated-orcid":false,"given":"Veluchamy Amutha","family":"Barathi","sequence":"first","affiliation":[{"name":"Translational Preclinical Model Platform, Singapore Eye Research Institute, 20 College Road, Singapore 169856, Singapore"},{"name":"Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, National University Hospital System, 10 Medical Dr, Singapore 117597, Singapore"},{"name":"Eye-Academic Clinical Program, DUKE-National University of Singapore Gr Medical School, 8 College Road, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candice E. H.","family":"Ho","sequence":"additional","affiliation":[{"name":"Translational Preclinical Model Platform, Singapore Eye Research Institute, 20 College Road, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3986-6552","authenticated-orcid":false,"given":"Louis","family":"Tong","sequence":"additional","affiliation":[{"name":"Eye-Academic Clinical Program, DUKE-National University of Singapore Gr Medical School, 8 College Road, Singapore 169857, Singapore"},{"name":"Corneal and External Eye Disease, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore"},{"name":"Ocular Surface Research Group, Singapore Eye Research Institute, 20 College Road, Singapore 169856, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/eye.2011.144","article-title":"Prevalence and risk factors for refractive errors and ocular biometry parameters in an elderly Asian population: The Singapore Longitudinal Aging Study (SLAS)","volume":"25","author":"Tan","year":"2011","journal-title":"Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1475-1313.2005.00298.x","article-title":"Myopia and associated pathological complications","volume":"25","author":"Saw","year":"2005","journal-title":"Ophthalmic Physiol. 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