Abstract
Purpose: :
To elucidate the role of autophagy in retinal ganglion cells (RGCs) of the retina after chronic intraocular pressure (IOP) elevation in a chronic hypertension model of glaucoma.
Methods: :
Induction of autophagy is manifested by accumulation of autophagosomes (APs), observable under transmission electron microscopy (EM). Two hallmarks of autophagy, the microtubule-associated protein light chain 3 (LC3) and beclin-1, were explored by biochemical and confocal microscopic analyses of retinal tissues.
Results: :
Under EM, APs were markedly accumulated in the dendrites and axons of RGCs in the ganglion cell layer (GCL) and inner plexiform layer (IPL) of the retina after IOP elevation. Western blot analysis showed that LC3-II and beclin-1 were shortly upregulated at 1 to 2 weeks after IOP elevation and decreased thereafter. LC-3 immmunostaining was mainly located in the GCL and IPL under confocal microscopy. These results show that the autophagy pathway is initially activated after IOP elevation. However, RGCs significantly decreased after 4 weeks of IOP elevation in our model, which is after the decrease of autophagic activation.
Conclusions: :
We propose that activation of autophagy serves as a protective mechanism in RGCs for maintaining homeostasis after chronic IOP elevation.