Background and purpose: Pathologic myopia (PM) is a severe form of myopia associated with structural changes in the eye, leading to vision impairment. Identifying genetic factors that contribute to PM can enhance the treatment of the condition. This study aimed to investigate the association between the GPR97 and PM and to evaluate the impact of glucocorticoid treatment on PM. Experimental approach: A cohort of 412 sporadic PM patients underwent Sanger sequencing and genotyping for GPR97 gene variants. Thirty-one PM patients with various GPR97 genotypes received glucocorticoid and brinzolamide treatment over 24 months. Real-time PCR was employed to examine the target gene mRNA expression. A scratch assay was performed to detect cell migration ability. Findings/Results: A significant association was identified between GPR97 rs76688596 genotypes and PM occurrence. The CC genotype was linked to elevated intraocular pressure (IOP). In human scleral fibroblasts, overexpression of GPR97 Arg396 resulted in upregulation of IOP-related genes serine/arginine-rich splicing factor 3, peptidyl-prolyl cis-trans isomerase 4, peptidyl-prolyl cis-trans isomerase 5, and nuclear receptor subfamily 3 group C member 1. The GPR97 Arg396 mutation inhibited the glucocorticoid-GPR97 axis and reduced cell migration ability. Clinically, CC genotype carriers exhibited significant improvements in axial length, spherical equivalent, IOP, best-corrected visual acuity, and visual field mean sensitivity with glucocorticoid treatment. Conclusion and implications: The study revealed that the GPR97 rs76688596 G > C variant is associated with PM pathogenesis, influencing gene expression related to IOP. The differential response to glucocorticoid treatment among GPR97 genotypes suggests personalized therapeutic potential.
Zhao et al. (Sun,) studied this question.