Primary Cilia of Astrocytes in the Retina in Development and Disease

Abstract

Purpose Defects in primary cilia and ciliary signaling are associated with an array of neurodegenerative diseases. Primary cilia are sensory organelles that transmit and regulate various cellular communication pathways, including the significant Sonic hedgehog and Wnt signal pathways. Extensive studies have shown that neuronal cilia in the central nervous system contribute to early patterning, neuronal maturation, and survival. The behavior of cilia on astrocytes in glaucoma and aging remains poorly understood. This study used rodent and human retinal astrocytes to examine primary cilia and their alteration during aging and disease. Methods Retinal flatmounts from wild-type mice, one macaque, and two humans were immunostained for astrocyte (glial fibrillary acidic protein [GFAP]) and ciliary (Arl13b and gamma-tubulin) markers and analyzed by confocal microscopy. Ciliation was also assessed in models of ocular hypertension and optic nerve crush prepared in 3- and 20-month-old mice. Results Primary cilia were found in most of the mouse retinal astrocytes (98.81% ± 4.03% in 3-month-old mice and 91.05% ± 9.95% in 20-month-old mice). Interestingly, astrocyte ciliation was significantly reduced in the peripheral retinas of the aged mice. Both human and nonhuman primate retinas expressed primary cilia in bundle-shaped and star-shaped GFAP-positive astrocytes. As a result of alterations in the primary cilia of retinal astrocytes, response processes varied in different glaucoma mouse models, including the ocular hypertension and optic nerve crush models. Conclusions Aged and diseased mouse retinas demonstrated a novel alteration of their ciliary profile. These findings suggest the possibility that primary cilia contribute to age-associated retinal diseases.