Ocular Ciliopathies: Genetic and Mechanistic Insights into Developing Therapies

Abstract

Developing suitable medicines for genetic diseases requires a detailed understanding of not only the pathways that cause the disease, but also the identification of the genetic components involved in disease manifestation. This article focuses on the complexities associated with ocular ciliopathies - a class of debilitating disorders of the eye caused by ciliary dysfunction. Ciliated cell types have been identified in both the anterior and posterior segments of the eye. Photoreceptors (rods and cones) are the most studied ciliated neurons in the retina, which is located in the posterior eye. The photoreceptors contain a specialized lightsensing outer segment, or cilium. Any defects in the development or maintenance of the outer segment can result in severe retinal ciliopathies, such as retinitis pigmentosa and Leber congenital amaurosis. A role of cilia in the cell types involved in regulating aqueous fluid outflow in the anterior segment of the eye has also been recognized. Defects in these cell types are frequently associated with some forms of glaucoma. Here, we will discuss the significance of understanding the genetic heterogeneity and the pathogenesis of ocular ciliopathies to develop suitable treatment strategies for these blinding disorders.

Keywords: Leber congenital amaurosis; congenital amaurosis; genetic diseases; ocular ciliopathies; photoreceptors; posterior eye..

Fig. (1)

A schematic diagram of the side-view of the eye ball (A) and the photoreceptors (B) is depicted. BB: basal bodies; ER: endoplasmic reticulum; G: Golgi; M: mitochondria; TZ: transition zone.

Fig. (2)

Ciliary staining of endothelial receptors: A: Ciliated HUVECs were immunostained with TEK (green; Proteintech) or CYP1B1 (green; Proteintech) and acetylated-α-tubulin (ACT-TUB; cilia marker; red; Sigma) antibodies. Merge image shows co-localization of the red and the green signals. Arrows indicate cilia in the TEK-stained panel whereas in the CYP1B1-stained panel, arrows indicate the CYP1B1-immunoreactive signal at the base of cilia. B: Ciliated HUVECs were stained with VEGFR2 (red; Sigma) or ARL13B (ADP-ribosylation Factor-like 13B; ciliary marker; green; Proteintech). Arrows indicate ciliary staining of VEGFR2.