Autophagy is reported to have important roles in relation to regulated cell death pathways and neurodegeneration. This study used chronic hypertensive glaucoma rat model to investigate whether the autophagy pathway has a role in the apoptosis of retinal ganglion cells (RGCs) after chronic intraocular pressure (IOP) elevation. Under electron microscopy, autophagosomes were markedly accumulated in the dendrites and cytoplasm of RGCs after IOP elevation. Western blot analysis showed that LC3-II/LC3-I and beclin-1 were upregulated throughout the 8-weeks period after IOP elevation. The pattern of LC3 immunostaining showed autophagy activation in the cytoplasm of RGCs to increase and peak at 4 weeks after IOP elevation. Most of these LC3B-positive RGCs underwent apoptosis by terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling, and inhibition of autophagy with 3-methyladenine decreased RGC apoptosis. The activated pattern shows that autophagy is initially activated in the dendrites of the RGCs, but, thereafter autophagy is mainly activated in the cytoplasm of RGCs. This may show that autophagy is differently regulated in different compartments of the neuron. This present study showed that autophgy is activated in RGCs and has a role in autophagic cell death after chronic IOP elevation.

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Purpose To investigate the clinical characteristics according to the location of focal lamina cribrosa (LC) defects and its associated ocular features. Patients and methods A total of 139 openangle glaucoma patients underwent Spectralis optical coherence tomography (OCT) with enhanced depth imaging. Alterations in the contour of the LC were investigated to find focal LC defects. The location of the visible LC defect from the neural canal wall (farperipheral and mid-peripheral) and clockhour position (superotemporal, temporal and inferotemporal) were classified. Disc ovality ratio and disc-foveal angle were measured from disc and retinal nerve fiber layer (RNFL) photographs. The disc tilt degree was measured using a Heidelberg Retina Tomograph (HRT) III system. The en face OCT image of the disc scans was registered to the disc and RNFL photographs, to determine whether the focal LC defects corresponded spatially to the glaucomatous damage location. Results Eyes with far-peripheral LC defects were significantly myopic and had a higher disc ovality ratio. The disc tilt degree obtained by HRT revealed significant temporal disc tilt in eyes with temporal LC defects (Po0.001). Eyes with inferotemporal LC defects had a significantly larger discfoveal angle (P = 0.027). The inferotemporal LC defects corresponded to the location of glaucomatous damage in 81.6%; however, only 46.2% of eyes with a superotemporal LC defect and 3.2% of eyes with a temporal LC defect corresponded spatially with the glaucomatous damage location. Conclusions The clinical characteristics and association with glaucomatous damage location were different according to the location of focal LC defect.