Primary cilia in ocular development, maintenance and disease

Primary cilia are evolutionarily conserved, microtubule-based organelles that serve as sensory hubs, integrating extracellular signals with intracellular responses. In the eye, they are broadly distributed across the cornea, lens, trabecular meshwork, Schlemm’s canal, neural retina, and retinal pigment epithelium (RPE), where they contribute to development, homeostasis, and, in some tissues, responses to injury. Photoreceptor outer segments are highly specialized ciliary compartments critical for phototransduction, while cilia in other ocular cells regulate signaling pathways, mechanosensation, and tissue polarity. Disruption of ocular ciliogenesis or ciliary signaling causes a spectrum of disorders in which ciliary dysfunction is a primary pathogenic mechanism, collectively termed ciliopathies. These include nonsyndromic diseases such as ciliary gene-associated forms of retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), as well as syndromic conditions like Lowe syndrome (oculocerebrorenal syndrome of Lowe), Bardet-Biedl syndrome (BBS), Usher syndrome (USH), Joubert syndrome (JBTS), Meckel syndrome (MKS), Senior-Løken syndrome, and Alström syndrome (ALMS). In addition, accumulating evidence implicates ciliary dysfunction in corneal disorders and glaucoma, although direct causal relationships remain incompletely established in many cases. Genetic advances have identified over 100 ciliary genes linked to ocular disease, revealing extensive heterogeneity and conserved pathogenic mechanisms. Recent progress in translational research has opened new therapeutic avenues, including adeno-associated virus (AAV)-mediated gene augmentation, CRISPR-based genome editing, antisense oligonucleotide (AON) therapy, stem cell-based regeneration, and pharmacological modulation of ciliary signaling. This review summarizes the current understanding of ciliary dynamics in ocular development and disease, highlights emerging therapeutic strategies, and discusses key questions to guide future research on ocular ciliopathies.