The Role of circFAM53B in Regulating Choroidal Vascular Function in Pathological Myopia

Myopia has reached epidemic levels worldwide, in which pathological myopia can lead to irreversible visual loss from associated ocular complications. This study aimed to investigate the role of circular RNA circFAM53B in choroidal dysfunction in pathological myopia progression.

We established In vitro and in vivo models to simulate hypoxic and oxidative injuries to rhesus macaque choroid-retina endothelial cells, which may contribute to the choroidal vascular dysfunction in pathological myopia.

RNA sequencing and comprehensive bioinformatics analyses revealed widespread differential expression of circular RNAs in injured choroidal cells, with circFAM53B being notably and consistently upregulated under both hypoxic and oxidative conditions. Functional assays demonstrated that small interfering RNA (siRNA)-mediated knockdown of circFAM53B significantly enhanced viability, migration and tubulogenesis of choroidal endothelial cells while suppressing apoptosis. Mechanistic studies found that circFAM53B can act as a sponge for miR-1248, consequently relieving the inhibition of miR-1248 on its target THBS1 and leading to THBS1 upregulation. Form-deprivation myopia in guinea pigs also showed substantially elevated circFAM53B expression in myopic eye tissues over time.

Our results shed light on the involvement of the circFAM53B/miR-1248/THBS1 pathway in the decline of choroidal function observed in pathological myopia, expanding current understanding of the molecular mechanisms driving myopia development and offering potential therapeutic targets for choroid-related myopia.