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Impact of PTEN/SOCS3 deletion on amelioration of dendritic shrinkage of retinal ganglion cells after optic nerve injury.
Exp Eye Res. 2020 03; 192:107938.EE

Abstract

Retinal ganglion cell (RGC) degeneration, leading to irreversible blindness in chronic optic neuropathies, commonly begins with dendritic shrinkage followed by axon degeneration. Although limited axon regeneration in the optic nerve is possible with a genetic deletion of PTEN/SOCS3 after optic nerve injury, the roles of PTEN/SOCS3 on dendritic preservation and regeneration remain unclear. This study investigated the effect of PTEN/SOCS3 genetic deletion on the structural integrity of RGC dendrites and axons in the retina following optic nerve crush. Using time-lapse, in vivo confocal scanning laser ophthalmoscopy to serially image dendritic and axonal arborizations of RGCs over six months after injury, RGC dendrites and axons were only preserved in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice, and axons in the retina regenerated at a rate of 21.1 μm/day and 15.5 μm/day, respectively. By contrast, dendritic complexity significantly decreased in Thy-1-YFP-SOCS3-/- and control mice at a rate of 7.0 %/day and 7.1 %/day, respectively, and no axon regeneration in the retina was observed. RGC survival probability was higher in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice compared with Thy-1-YFP-SOCS3-/- and control mice. The differential responses between the transgenic mice demonstrate that although a genetic deletion of PTEN, SOCS3, or PTEN/SOCS3 allows partial axon regeneration in the optic nerve after optic nerve crush, a deletion of PTEN, but not SOCS3, ameliorates RGC dendritic shrinkage. This shows that the signaling pathways involved in promoting axon regeneration do not equally contribute to the preservation of dendrites, which is crucial to the translational application of neuroregenerative therapies for visual restoration.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: hmak@cuhk.edu.hk.Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: shukhanng.heidi@gmail.com.Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: tianmin.ren.16@link.cuhk.edu.hk.Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: kevincyip@gmail.com.Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: cksleung@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31972211

Citation

Mak, Heather K., et al. "Impact of PTEN/SOCS3 Deletion On Amelioration of Dendritic Shrinkage of Retinal Ganglion Cells After Optic Nerve Injury." Experimental Eye Research, vol. 192, 2020, p. 107938.
Mak HK, Ng SH, Ren T, et al. Impact of PTEN/SOCS3 deletion on amelioration of dendritic shrinkage of retinal ganglion cells after optic nerve injury. Exp Eye Res. 2020;192:107938.
Mak, H. K., Ng, S. H., Ren, T., Ye, C., & Leung, C. K. (2020). Impact of PTEN/SOCS3 deletion on amelioration of dendritic shrinkage of retinal ganglion cells after optic nerve injury. Experimental Eye Research, 192, 107938. https://doi.org/10.1016/j.exer.2020.107938
Mak HK, et al. Impact of PTEN/SOCS3 Deletion On Amelioration of Dendritic Shrinkage of Retinal Ganglion Cells After Optic Nerve Injury. Exp Eye Res. 2020;192:107938. PubMed PMID: 31972211.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of PTEN/SOCS3 deletion on amelioration of dendritic shrinkage of retinal ganglion cells after optic nerve injury. AU - Mak,Heather K, AU - Ng,Shuk Han, AU - Ren,Tianmin, AU - Ye,Cong, AU - Leung,Christopher Kai-Shun, Y1 - 2020/01/21/ PY - 2019/04/17/received PY - 2020/01/02/revised PY - 2020/01/16/accepted PY - 2020/1/24/pubmed PY - 2020/10/24/medline PY - 2020/1/24/entrez KW - Dendritic shrinkage KW - Optic nerve injury KW - Phosphatase and tensin homolog (PTEN) KW - Retinal ganglion cell KW - Suppressor of cytokine signaling 3 (SOCS3) SP - 107938 EP - 107938 JF - Experimental eye research JO - Exp Eye Res VL - 192 N2 - Retinal ganglion cell (RGC) degeneration, leading to irreversible blindness in chronic optic neuropathies, commonly begins with dendritic shrinkage followed by axon degeneration. Although limited axon regeneration in the optic nerve is possible with a genetic deletion of PTEN/SOCS3 after optic nerve injury, the roles of PTEN/SOCS3 on dendritic preservation and regeneration remain unclear. This study investigated the effect of PTEN/SOCS3 genetic deletion on the structural integrity of RGC dendrites and axons in the retina following optic nerve crush. Using time-lapse, in vivo confocal scanning laser ophthalmoscopy to serially image dendritic and axonal arborizations of RGCs over six months after injury, RGC dendrites and axons were only preserved in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice, and axons in the retina regenerated at a rate of 21.1 μm/day and 15.5 μm/day, respectively. By contrast, dendritic complexity significantly decreased in Thy-1-YFP-SOCS3-/- and control mice at a rate of 7.0 %/day and 7.1 %/day, respectively, and no axon regeneration in the retina was observed. RGC survival probability was higher in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice compared with Thy-1-YFP-SOCS3-/- and control mice. The differential responses between the transgenic mice demonstrate that although a genetic deletion of PTEN, SOCS3, or PTEN/SOCS3 allows partial axon regeneration in the optic nerve after optic nerve crush, a deletion of PTEN, but not SOCS3, ameliorates RGC dendritic shrinkage. This shows that the signaling pathways involved in promoting axon regeneration do not equally contribute to the preservation of dendrites, which is crucial to the translational application of neuroregenerative therapies for visual restoration. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/31972211/Impact_of_PTEN/SOCS3_deletion_on_amelioration_of_dendritic_shrinkage_of_retinal_ganglion_cells_after_optic_nerve_injury_ DB - PRIME DP - Unbound Medicine ER -