Retinal ciliopathies through the lens of Bardet-Biedl Syndrome: Past, present and future

The primary cilium is a highly specialized and evolutionary conserved organelle in eukaryotes that plays a significant role in cell signaling and trafficking. Over the past few decades tremendous progress has been made in understanding the physiology of cilia and the underlying pathomechanisms of various ciliopathies. Syndromic ciliopathies consist of a group of disorders caused by ciliary dysfunction or abnormal ciliogenesis. These disorders have multiorgan involvement in addition to retinal degeneration underscoring the ubiquitous distribution of primary cilia in different cell types. Genotype-phenotype correlation is often challenging due to the allelic heterogeneity and pleiotropy of these disorders. In this review, we discuss the clinical and genetic features of syndromic ciliopathies with a focus on Bardet-Biedl syndrome (BBS) as a representative disorder. We discuss the structure and function of primary cilia and their role in retinal photoreceptors. We describe the progress made thus far in understanding the functional and genetic characterization including expression quantitative trait locus (eQTL) analysis of BBS genes. In the future directions section, we discuss the emerging technologies, such as gene therapy, as well as anticipated challenges and their implications in therapeutic development for ciliopathies.

Automated summary

The primary cilium is a specialized organelle in eukaryotes that plays an important role in cell signaling and transportation. Ciliopathies are a group of disorders caused by ciliary dysfunction or abnormal ciliogenesis, with multiorgan involvement. Understanding the genetics and clinical features of ciliopathies, such as Bardet-Biedl syndrome, is challenging but crucial for therapeutic development. This review discusses the structure and function of primary cilia, their role in retinal photoreceptors, and the progress made in understanding ciliopathies.