Impact of PTEN/SOCS3 deletion on amelioration of dendritic shrinkage of retinal ganglion cells after optic nerve injury

• Published in: Experimental eye research Vol. 192; p. 107938
• Main Authors: Mak, Heather K., Ng, Shuk Han, Ren, Tianmin, Ye, Cong, Leung, Christopher Kai-shun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2020
• Subjects: Dendritic shrinkage; Optic nerve injury; Phosphatase and tensin homolog (PTEN); Retinal ganglion cell; Suppressor of cytokine signaling 3 (SOCS3); PBS; YFP; Suppressor of cytokine signaling 3 (SOCS3); BDNF; PTEN; JAK/STAT; Optic nerve injury; CSLO; Dendritic shrinkage; Phosphatase and tensin homolog (PTEN); RGC; TUJ1; CTB; SOCS3; AAV; mTOR; NGS; SMI-32; Retinal ganglion cell
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2020.107938

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. •PTEN, but not SOCS3, deletion ameliorates RGC dendritic shrinkage after ON crush.•Rate of dendritic shrinkage in SOCS3-deleted RGCs are no different from control.•SOCS3 deletion enhances axon regeneration in the optic nerve, but not the retina.•Intrinsic RGC axon and dendritic preservation mechanisms are molecularly distinct.•PTEN deletion shows aberrant axon regeneration in retina 6 months after ON crush.