Abstract
Purpose :
Strabismus, a condition characterized by misalignment of the eyes, is a common ophthalmic disorder affecting both children and adults. In our previous study, we identified the microsomal glutathione S-transferase 2 (MGST2) gene as one of the potential candidates for comitant strabismus-susceptibility in a Japanese population. MGST2 gene belongs to the membrane-associated protein involved in the generation of pro-inflammatory mediators, and also in protection against oxidative stress by decreasing the reactivity of oxidized lipids. In this study, we investigated the roles of the MGST2 gene in eye development, eye alignment, and overall eye morphology.
Methods :
MGST2 gene knockout (KO) mice were generated by CRISPR/Cas9-mediated gene editing with guide RNAs targeting the MGST2 exon 2. The Ocular morphology of 5-month (20-week)-old wild-type (WT) mice (n=5, males) and homozygous (MGST2-/-) mice (n=5, males) were analyzed using high-resolution images obtained by a magnetic resonance imaging (MRI) machine for small animals. Student’s t-test was used for statistical analysis.
Results :
The morphometric analyses showed that the eye volumes of MGST2-/- mice were increased by 5.6% compared with those of WT mice (WT: MGST2-/- = 22.1 ± 0.97: 23.4 ± 1.33 mm3, P=0.01). Furthermore, MGST2-/- mice also displayed a 3% increase in eye width in both horizontal (WT: MGST2-/- = 3.3 ± 0.05: 3.4 ± 0.06 mm, P=0.005) and equatorial planes (WT: MGST2-/- = 3.22 ± 0.05: 3.31 ± 0.05 mm, P=0.002), and a 2.4% increase in eye height in equatorial (WT: MGST2-/-= 3.15 ± 0.08: 3.23 ± 0.06 mm, P=0.016)and sagittal planes (WT: MGST2-/- = 3.26 ± 0.07: 3.34 ± 0.06 mm, P=0.025). There were no significant differences in the axis length and axis angle.
Conclusions :
MGST2 KO mice showed significantly larger height, width, and volume of the eyeballs than those of WT mice, indicating that the eyes of MGST2 KO mice were significantly enlarged. These morphological changes may be an underlying factor in the subgroup of strabismus. Further research such as molecular pathways and cell signaling is needed to understand the specific mechanisms, but these findings provide new insights into the pathogenesis of eye abnormalities.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.