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Vps35 haploinsufficiency results in degenerative-like deficit in mouse retinal ganglion neurons and impairment of optic nerve injury-induced gliosis.

Liu W, Tang FL, Erion J, Xiao H, Ye J, Xiong WC - Mol Brain (2014)

Bottom Line: VPS35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China. yejian1979@163.com.

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.

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VPS35 expression in mouse RGCs. Co-immunostaining analysis was carried out in cross sections from P30 Vps35+/+(A) and +/m(B-C) mouse retinas using indicated antibodies. GCL, ganglion cell layer; NL, neuroblast layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; OS, outer segment; IS, inner segment. Arrows indicate co-localization signals. Inserts are amplified images of the marked squares. Scale bar, 50 μm.
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Figure 2: VPS35 expression in mouse RGCs. Co-immunostaining analysis was carried out in cross sections from P30 Vps35+/+(A) and +/m(B-C) mouse retinas using indicated antibodies. GCL, ganglion cell layer; NL, neuroblast layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; OS, outer segment; IS, inner segment. Arrows indicate co-localization signals. Inserts are amplified images of the marked squares. Scale bar, 50 μm.

Mentions: Retinal ganglion cells (RGCs) are largely distributed in the GCL. We thus examined if VPS35 is expressed in RGCs by co-immunofluorescence staining analysis using anti-VPS35 or anti-β-gal antibodies in vps35+/+ or +/m retinas. As shown in Figure 2A, VPS35 was largely co-distributed with Tuj1, which recognizes neuronal class β-III tubulin in RGCs. It was undetectable in horizontal cells (marked by calbindin) and photoreceptor cells (by rhodopsin), but weakly detected in amacrine cells (viewed by calretinin) and glial cells (by GFAP) (Figures 2A-B). These results thus provide evidence for the selective expression of VPS35 in mouse RGCs.


Vps35 haploinsufficiency results in degenerative-like deficit in mouse retinal ganglion neurons and impairment of optic nerve injury-induced gliosis.

Liu W, Tang FL, Erion J, Xiao H, Ye J, Xiong WC - Mol Brain (2014)

VPS35 expression in mouse RGCs. Co-immunostaining analysis was carried out in cross sections from P30 Vps35+/+(A) and +/m(B-C) mouse retinas using indicated antibodies. GCL, ganglion cell layer; NL, neuroblast layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; OS, outer segment; IS, inner segment. Arrows indicate co-localization signals. Inserts are amplified images of the marked squares. Scale bar, 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4016418&req=5

Figure 2: VPS35 expression in mouse RGCs. Co-immunostaining analysis was carried out in cross sections from P30 Vps35+/+(A) and +/m(B-C) mouse retinas using indicated antibodies. GCL, ganglion cell layer; NL, neuroblast layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; OS, outer segment; IS, inner segment. Arrows indicate co-localization signals. Inserts are amplified images of the marked squares. Scale bar, 50 μm.
Mentions: Retinal ganglion cells (RGCs) are largely distributed in the GCL. We thus examined if VPS35 is expressed in RGCs by co-immunofluorescence staining analysis using anti-VPS35 or anti-β-gal antibodies in vps35+/+ or +/m retinas. As shown in Figure 2A, VPS35 was largely co-distributed with Tuj1, which recognizes neuronal class β-III tubulin in RGCs. It was undetectable in horizontal cells (marked by calbindin) and photoreceptor cells (by rhodopsin), but weakly detected in amacrine cells (viewed by calretinin) and glial cells (by GFAP) (Figures 2A-B). These results thus provide evidence for the selective expression of VPS35 in mouse RGCs.

Bottom Line: VPS35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China. yejian1979@163.com.

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.

Show MeSH
Related in: MedlinePlus