What is it about?

Myopia, a common refractive error disease worldwide, is defined by the lengthening of the eye, leading to vision abnormalities. Understanding the genetic factors involved in myopia is important for building treatment and protective steps. Unfortunately, only a small number of genes with well-defined functions have been linked with myopia. In this work, we found that the homozygous TGM2-deleted gene in mice shielded against the development of myopia by slowing down the lengthening of the eye. The success of gene knockdown was proven by getting a 60 percent decrease 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 different transglutaminase inhibitors led to the down-regulation of TGM-2 expression, with the most significant decrease found with specific TGM-2 inhibitors. Additionally, the study found that the drug blocking of muscarinic receptors also slowed the development of myopia in mice, and this effect was accompanied by a drop in TGM-2 enzyme expression. Specifically, mice with homozygous mAChR5, mAChR1, and/or mAChR4 and knockout mice showed 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, −2.2, and −4.7, respectively; p < 0.05). These results strongly suggest that both TGM-2 and muscarinic receptors play key roles in the development of myopia, and stopping these factors could possibly be useful in interfering with the growth of this condition. In conclusion, targeting TGM-2 may have a positive effect regarding myopia, and this may also be at least partly be the cause of anti-muscarinic drugs in myopia. Further studies should examine the relationship between TGM-2 and muscarinic receptors, as well as the changes in other extracellular matrix genes involved with growth during the development of myopia.

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Why is it important?

Myopia is a worldwide problem

Perspectives

Inhibiting one molecule may be sufficient to halt myopia

Prof Louis Tong
National University of Singapore

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This page is a summary of: Molecular Basis of Transglutaminase-2 and Muscarinic Cholinergic Receptors in Experimental Myopia: A Target for Myopia Treatment, Biomolecules, June 2023, MDPI AG,
DOI: 10.3390/biom13071045.
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