Characterization of lncRNA and mRNA profiles in ciliary body in experimental myopia

Myopia has become a public health issue globally and is a leading cause of blindness in East Asia district, where the prevalence of myopia is high, affecting 80%–90% of young adults in the region and 10%–30% of the adult population in many countries (Wu et al., 2016). It is predicted that approximately five billion people will suffer from myopia by 2050, accounting for nearly fifty percent of the world's population, suggesting a soaring prevalence of myopia worldwide and an urgent requirement to prevent the development of myopia. Among them, the prevalence of high myopia in the world population will increase to 9.8% by 2050, equivalent to about 1 billion people suffering from high myopia (Holden et al., 2016; Wu et al., 2019), which may result in higher risks of uncorrectable visual impairment or blindness such as retinal detachment, glaucoma, and macular holes (Bullimore and Brennan, 2019). Studies have pointed out that axial elongation in myopic eyes is primarily regulated by the local microenvironment of posterior segment structures, such as the retina, choroid, and scleral tissues (Wallman and Winawer, 2004; Harper and Summers, 2015; El-Nimri et al., 2022; Mathis et al., 2014). Further, it has been demonstrated that multiple molecular mechanisms in these structures are involved in the development of myopia (Mathis et al., 2023; Guo et al., 2020; McBrien 2013; Wu et al., 2018; Zhou et al., 2020). Nevertheless, the pathogenic mechanism of myopia is still unclear.

Except for the well-known genetic factors, environmental factors, such as prolonged near-work activities and reduced outdoor interaction, play a crucial role in degrading the image quality in the retina, which may be the critical causative factors of myopia (Wiesel and Raviola, 1977; Mutti et al., 2002). Theoretically, the blurred vision may probably be caused by the disturbance of ciliary body accommodation due to long-term near work, which results in accommodative lag and hyperopic defocus, ultimately leading to axial elongation and myopia. Nevertheless, the detailed mechanism needs to be further explored (Wallman and Winawer, 2004). Moreover, given the strong correlation between the development of myopia and prolonged near work, the ciliary body, the initiating factor responding to accommodation, has also been studied for changes in its biological characteristics during the development of myopia. Studies have shown that the ciliary muscles or ciliary body of myopic eyes are thicker or larger than those of normal eyes in both human volunteers and animal models, showing decreased movement during accommodation (Bailey et al., 2008; Fernández-Vigo et al., 2020; Jeon et al., 2012; Buckhurst et al., 2013). On the contrary, researchers (Wagner et al., 2019) have uncovered that the ciliary muscles got thinner after sustained near work in myopic human subjects. Experimental myopic animal models have also shown that the ciliary muscles got thinner and shorter in myopic eyes than in untreated eyes (Pucker et al., 2020). Although researchers have studied the role of the ciliary body in the development of myopia in terms of its morphology and regulatory function, the pathogenic mechanism at the molecular level needs to be further elucidated.

Long non-coding RNAs (lncRNAs), defined as transcripts longer than 200 nucleotides with no protein-coding potential, have been shown to play critical roles in regulating gene expression at the epigenetic, transcriptional, and translational levels (Batista and Chang, 2013). RNA sequencing (RNA-seq), a high-throughput approach, can identify specific lncRNAs, analyze gene expression, and reveal novel RNA species. It has been confirmed that lncRNAs play key roles in regulating cell proliferation, apoptosis, differentiation, immune responses, oxidative stress, and inflammation in biological and pathological processes (Wan et al., 2017). Importantly, researchers show that lncRNAs may exert vital roles in the pathogenesis and regulation of several ocular diseases, such as glaucoma (Zheng et al., 2020), cataract (Han et al., 2022), uveitis (Ni et al., 2022), retinal diseases (Ni et al., 2021), and retinoblastoma (He et al., 2020). Meanwhile, RNA-seq has also identified the potentially pathogenic lncRNAs mainly involved in cytokine-cytokine receptor interactions, retinol metabolism, and ECM-receptor interaction pathways in posterior segment tissues of myopic animal models (Li et al., 2022; Geng et al., 2020). Nevertheless, the expression profiles of lncRNAs and mRNAs in ciliary body have not been fully investigated in experimental myopic animal models. Thus, in the present study, we used RNA-seq analysis to explore the related molecular atlas in the ciliary body involved in the pathogenesis of myopia in LIM animal models that could mimic the role of the ciliary body during near work in human eyes. Our study will facilitate the understanding of the underlying molecular mechanisms in ciliary body involved in the occurrence and development of myopia.

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