Abstract
Tauopathy is a neurodegenerative condition associated with oligomeric tau formation through abnormal phosphorylation. We previously showed that tauopathy is involved in death of retinal ganglion cells (RGCs) after optic nerve crush (ONC). It has been proposed that glycogen synthase kinase 3β (GSK3β) is involved in the hyperphosphorylation of tau in Alzheimer's disease. To determine the roles of GSK3β in tauopathy-related death of RGCs, lithium chloride (LiCl), a GSK3β inhibitor, was injected intravitreally just after ONC. The neuroprotective effects of LiCl were determined by counting Tuj-1-stained RGCs on day 7. Changes of phosphorylated (ser 396) tau in the retina were determined by Simple Western analysis (WES) on day 3. Retinal GSK3β levels were determined by immunohistochemistry (IHC) and an ELISA. There was a 1.9- and 2.1-fold increase in the levels of phosphorylated tau monomers and dimers on day 3 after ONC. LiCl significantly suppressed the increase in the levels of phosphorylated tau induced by ONC. GSK3β was mainly present in somas of RGCs, and ELISA showed that retinal levels increased to 2.0-fold on day 7. IHC showed that the GSK3β expression increased over time and remained in RGCs that were poorly stained by Tuj-1. The GSK3β and tau expression was colocalized in RGCs. The number of RGCs decreased from 1881 ± 188 (sham control) to 1150 ± 192 cells/mm2 on day 7, and LiCl preserved the levels at 1548 ± 173 cells/mm2. Accordingly, GSK3β may be a promising target for some optic nerve injuries.