ABSTRACT
Objective:
To investigate the effect of
edaravone, a
free radical scavenger, on the
regulation of
retinal autophagy and the
protection of
photoreceptor cells at the early stage of experimental
retinal detachment (RD) in
rats.
Methods:
Fifty-one
adult male Sprague-Dawley rats were used for RD model establishment, and another 24
rats were served as PBS
injection group.The RD model was established via subretinal
injection of 0.5%
sodium hyaluronate into the right
eye of the
rats and the
rats with successful modeling were randomly divided into RD model group and
edaravone treatment group.The
rats in the
edaravone treatment group were given
edaravone of 3 mg/kg intraperitoneally, twice a day after modeling, and the
rats in the PBS
injection group and RD model group were given equal volume of
normal saline.
Rats were sacrificed on the 1st day, 3rd day and 7th day following modeling.The T-
superoxide dismutase (T-SOD) activity and
malondialdehyde (MDA) content in the
intraocular fluid was detected.The expression levels of
superoxide dismutase 2 (SOD2),
nuclear factor E2-related factor 2 (Nrf2),
autophagy related
gene 4 (Atg4),
microtubule-associated protein 1 light chain 3B (LC3B) and other
proteins in
retinal tissue were identified by
Western blot analysis.
TUNEL staining was performed on
paraffin sections of the whole eyeball to analyze the
apoptosis of
photoreceptor cells.The study protocol was approved by an
Ethics Committee of Xi'an Fourth
Hospital (No. 2016016). The use and care of
animals complied with the
Regulations on the
Administration of Experimental
Animals.
Results:
The RD area was more than 60% in
rat eyes of RD model.There were significant differences in MDA content and T-SOD activity among different groups at various
time points (MDA Fgroup=385.513, P<0.01; Ftime=13.021, P<0.01.T-SOD Fgroup=48.865, P<0.01; Ftime=7.700, P=0.003). Compared with the PBS
injection group, the MDA concentration was significantly increased and the T-SOD activity was significantly decreased in the RD group and
edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05). The MDA concentration was significantly reduced and the T-SOD activity was significantly elevated in the
edaravone treatment group on the 1st, 3rd and 7th day after modeling in comparison with those of the RD group (all at P<0.05). Compared with the PBS
injection group, the relative expression levels of SOD2 and Nrf2
proteins were significantly increased in the RD group and
edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased on the 1st, 3rd and 7th day after modeling (all at P<0.05). The expression level of SOD2 in the
edaravone treatment group was significantly higher than that in the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and the expression level of Nrf2 was significantly increased in the
edaravone treatment group on the 1st and 3rd day after modeling compared with that of the RD group (both at P<0.05), and the expression levels of Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased in the
edaravone treatment group on the 3rd day after modeling in comparison with those of the RD group (both at P<0.05). No significant
TUNEL positive
cells were observed in PBS
injection group at all
time points, and
TUNEL positive
cells were observed on the 1st, 3rd and 7th day after modeling in the RD group, and the expression level of
caspase-3 in the RD group was significantly increased in comparison with that of the PBS
injection group ( P<0.05). The
apoptosis of
photoreceptor cells and the expression level of
caspase-3 in
edaravone treatment group were significantly decreased in comparison with those of the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05).
Conclusions:
The
intraperitoneal injection of
edaravone, twice a day, can significantly improve the
antioxidant capacity of the
retina after experimental RD in
rats, regulate
retinal autophagy and reduce the
apoptosis of
photoreceptor cells in early-stage RD.