Activation of autophagy and paraptosis in rat retinal ganglion cells following acute intraocular hypertension / 国际眼科杂志(Guoji Yanke Zazhi)

ABSTRACT

· AIM:To study whether autophagy and paraptosis were activated in retinal ganglion cells (RGCs) after acute high intraocular pressure (lOP) 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 50μ m2 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 P＜ 0.05).LC3 positive expression was rarely detected in ganglion cell layer (GCL) in the normal control group and percentage of LC3 positive cells was 15.90％.Immumofluorescence analysis showed that the percentage of LC3 positive cells statistically increased in acute lOP groups when compared with control group (P＜0.05).The number of RGCs per 200μm in each group of acute lOP injury significantly decreased compared with the normal control group (P ＜ 0.05).Cytoplasmatic vacuolization were observed in RGCs at 3d after acute lOP injury and lasting to 8wk.TEM also revealed that a large number of cytoplasmic vacuoles were derived predominantly from the progressive swelling of mitochondria and/or endoplasmic reticulum (ER).· CONCLUSION: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.