Primary cilia in retinal pigment epithelium development and diseases

Abstract

Retinal pigment epithelium (RPE) is a highly polarized epithelial monolayer lying between the photoreceptor layer and the Bruch membrane. It is essential for vision through participating in many critical activities, including phagocytosis of photoreceptor outer segments, recycling the visual cycle‐related compounds, forming a barrier to control the transport of nutrients, ions, and water, and the removal of waste. Primary cilia are conservatively present in almost all the vertebrate cells and acts as a sensory organelle to control tissue development and homeostasis maintenance. Numerous studies reveal that abnormalities in RPE lead to various retinal diseases, such as age‐related macular degeneration and diabetic macular oedema, but the mechanism of primary cilia in these physiological and pathological activities remains to be elucidated. Herein, we summarize the functions of primary cilia in the RPE development and the mutations of ciliary genes identified in RPE‐related diseases. By highlighting the significance of primary cilia in regulating the physiological and pathological processes of RPE, we aim to provide novel insights for the treatment of RPE‐related retinal diseases.

TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa

“…These diseases are also known as ciliopathies, and although they can give rise to isolated RP, retinal defects are often linked to defects in other ciliated tissues ( 7 ). Interestingly, the RPE contains a primary cilium on its apical side, which is critical for RPE maturation and homeostasis maintenance ( 8 ), and RPE ciliary defects were recently associated with retinal ciliopathies ( 9 ).…”

Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation

“… 136 The vascular barrier controls the exchange of molecules and ions between blood and tissues and prevents dangerous substances from entering the tissues and causing damage. 137 , 140 Primary cilia are present in the eye, i.e., retinal pigment epithelium, and they carry out sensory function through various signaling pathways. 140 , 141 Loss of primary cilia is associated with several pathologies that have anomalies in these mechanisms, such as retinopathy and Leber congenital amaurosis.…”

“… 137 , 140 Primary cilia are present in the eye, i.e., retinal pigment epithelium, and they carry out sensory function through various signaling pathways. 140 , 141 Loss of primary cilia is associated with several pathologies that have anomalies in these mechanisms, such as retinopathy and Leber congenital amaurosis. 142 , 143 In the eye, the TM also contains primary cilia and these structures change with IOP.…”

Clinical and Molecular Aspects of C2orf71/PCARE in Retinal Diseases

“…Since the primary cilium is necessary for the complete maturation of the RPE, it is known that RPE maturation defects in ciliopathies occur before photoreceptor degeneration [ 88 ]. PSC-RPE obtained from knockdowns of ciliary-trafficking proteins and patients with ciliopathy exhibit immaturity, impaired development of apical processes, diminished functioning, and decreased expression of adult-specific genes [ 88 , 89 ]. Although it has been shown that ciliary gene mutations in RPE are linked to ciliary defects and retinal diseases, the exact causal relationship and underlying mechanisms by which primary cilia cause RPE-related diseases are still unknown.…”