title: Vps35 haploinsufficiency results in degenerative-like deficit in mouse retinal ganglion neurons and impairment of optic nerve injury-induced gliosis.
abstract: VPS35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD), both neuro-degeneration disorders. However, VPS35/retromer's function in retina or the contribution of Vps35-deficiency to retinal neuro-degenerative disorders has not been investigated. Here we provide evidence for a role of VPS35 in mouse retinal ganglion cell (RGC) survival and regeneration. VPS35 is selectively expressed in developing mouse RGCs. RGCs from young adult Vps35 heterozygotes (Vps35+/m) show degenerative-like features, such as dystrophic dendrites, reduced axon fibers, and increased TUNEL labeled RGCs. Additionally, gliosis in the optic nerve is transiently elevated in neonatal, but reduced in aged Vps35+/m mice. Optic nerve injury-induced gliosis is also attenuated in Vps35+/m mice. These results suggest that Vps35 is necessary for mouse RGC survival and regeneration, and Vps35-deficiency may contribute to the pathogenesis of retinal ganglion neuro-degeneration, a critical pathology leading to the blindness of many retinal degenerative disorders.
authors: Wei
authors: W
authors: Liu
authors: Fu-Lei
authors: FL
authors: Tang
authors: Joanna
authors: J
authors: Erion
authors: Hang
authors: H
authors: Xiao
authors: Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China. yejian1979@163.com.
authors: Jian
authors: J
authors: Ye
authors: Wen-Cheng
authors: WC
authors: Xiong
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D005911:Gliosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D057895:Haploinsufficiency; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D020221:Optic Nerve Injuries / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D017299:Rod Opsins / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D033921:Vesicular Transport Proteins; D000099210:Melanopsin; C101274:Vps35 protein, mouse