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.