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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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Increased TUNEL positive RGCs in vps35+/m retinas. TUNEL staining analysis was carried out in cross-sections of retinas from P7 (A) and P30 (B) vps35+/+ and +/m mice . GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer. Scale bar, 50 μm. The TUNEL+ cells in GCL were quantified and showed as mean +/- SEM (n = 3) in (C). *, P < 0.05.
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Figure 5: Increased TUNEL positive RGCs in vps35+/m retinas. TUNEL staining analysis was carried out in cross-sections of retinas from P7 (A) and P30 (B) vps35+/+ and +/m mice . GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer. Scale bar, 50 μm. The TUNEL+ cells in GCL were quantified and showed as mean +/- SEM (n = 3) in (C). *, P < 0.05.

Mentions: We then asked if VPS35 plays a role in mouse RGC survival. TUNEL assay, which label DNA damaged cells, was carried out in vps35+/+ and +/m retinas. Remarkably, increased TUNEL positive cells, particularly in the RGC layer of both P7 and P30 vps35+/m retina, were detected as compared to that of same age groups of vps35+/+ controls (Figure 5). Thus, these results support the view for a critical role of VPS35 in suppressing developing RGC degeneration.


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)

Increased TUNEL positive RGCs in vps35+/m retinas. TUNEL staining analysis was carried out in cross-sections of retinas from P7 (A) and P30 (B) vps35+/+ and +/m mice . GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer. Scale bar, 50 μm. The TUNEL+ cells in GCL were quantified and showed as mean +/- SEM (n = 3) in (C). *, P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Increased TUNEL positive RGCs in vps35+/m retinas. TUNEL staining analysis was carried out in cross-sections of retinas from P7 (A) and P30 (B) vps35+/+ and +/m mice . GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer. Scale bar, 50 μm. The TUNEL+ cells in GCL were quantified and showed as mean +/- SEM (n = 3) in (C). *, P < 0.05.
Mentions: We then asked if VPS35 plays a role in mouse RGC survival. TUNEL assay, which label DNA damaged cells, was carried out in vps35+/+ and +/m retinas. Remarkably, increased TUNEL positive cells, particularly in the RGC layer of both P7 and P30 vps35+/m retina, were detected as compared to that of same age groups of vps35+/+ controls (Figure 5). Thus, these results support the view for a critical role of VPS35 in suppressing developing RGC degeneration.

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