Activation of autophagy and paraptosis in rat retinal ganglion cells following acute intraocular hypertension

AIM: To study whether autophagy and paraptosis were activated in retinal ganglion cells(RGCs)after acute high intraocular pressure(IOP)in an experimental rat model and to explore the possible underlying mechanisms. METHODS: A total of 50 male Sprague-Dawley(SD)rats were randomly divided into normal control group, and 3d, 1, 4, 8wk group after acute elevated intraocular pressure(IOP)(n=10 per group). Acute intraocular hypertension model was established by anterior chamber perfusion of normal saline in the right eye. The expression levels of microtubule-associated protein 1 light chain 3(LC3)was measured by immumofluorescence method. To determine whether autophagy and paraptosis were activated. Retinal sections were examined by transmission electron microscopy(TEM). Autophagosomes and cytoplasmic vacuoles in the cytoplasm of RGCs were measured. RESULTS: TEM analysis revealed that double- and multiple-membrane vacuoles containing electron-dense materials of autophagosomes were found in RGCs. The number of autophagosomes per 50μm2 were 0.79±0.43, 2.14±0.36, 2.29±0.47, 1.57±0.51 and 1.21±0.43 in the normal control group and in acute IOP group at 3d, 1wk, 4wk, 8wk, respectively. The number of autophagosomes markedly increased in the cytoplasm of RGCs at 3d, 1wk, 4wk, 8wk groups than those in the normal control group(all at PPPCONCLUSION: Autophagy and paraptosis participate in the death of RGCs under transiently elevated intraocular pressure. Different types of programmed cell death(PCD), coexistence of multiple cell death forms or a single cell death form, participates in the pathogenesis of acute elevation of intraocular pressure.