Objective To investigate the effects of the ferroptosis inhibitor Ferrostatin-1 on the apoptosis of photore-ceptor cells and the Notch pathway in rats with retinal photochemical damage(RPD).Methods Male Sprague-Dawley(SD)rats were randomly divided into the Control group(normally fed rats,intraperitoneal injection of an equal volume of saline),RPD group(RPD model rats,intraperitoneal injection of an equal volume of saline),Ferrostatin-1 group(RPD model rats,intraperitoneal injection of 5 mg·kg-1 Ferrostatin-1),and Ferrostatin-1+JFC group[RPD model rats,intrap-eritoneal injection of 5 mg·kg-1 Ferrostatin-1 and 0.5 mg·kg-1 Jagged1/FC chimeric protein(JFC,a Notch pathway acti-vator)],with 15 rats in each group.The retinal histopathology of rats in each group was evaluated via hematoxylin-eosin(HE)staining.The apoptosis of photoreceptor cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay.The expression level of ferrous ions(Fe2+),lactate dehydrogenase(LDH),malondialde-hyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in retinal tissues was measured using corresponding kits.Western blot was performed to assess the protein expression of transferrin receptor protein 1(TfR1),divalent metal transporter 1(DMT1),nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),recombinant glutathione peroxidase 4(GPX4),cleaved Caspase-3,Notch,and hairy and enhancer of split 1(Hes1).Results The thickness of the outer nuclear layer(ONL)in the Control group,RPD group,Ferrostatin-1 group,and Fer-rostatin-1+JFC group was(35.24±1.76)μm,(16.83±1.14)μm,(27.56±1.39)μm,and(21.48±1.23)μm,respec-tively;the apoptosis rate of photoreceptor cells in the four groups was(1.32±0.07)％,(18.57±1.63)％,(9.61±1.04)％,and(15.43±1.38)％,respectively.Compared with the Ferrostatin-1 group,the Ferrostatin-1+JFC group exhib-ited an aggravated retinal damage level,reduced ONL thickness,and increased apoptosis rate,and the differences were statistically significant(all P＜0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expres-sion level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the RPD group were higher than those in the Control group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Control group,and the differences were statistically significant(all P＜0.05).Compared with the RPD group,the Ferrostatin-1 group displayed a decrease in the expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 but an increase in the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4,and the differences were statistically significant(all P＜0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the Ferrostatin-1+JFC group were higher than those in the Ferrostatin-1 group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Ferrostatin-1 group,and the differences were statistically significant(all P＜0.05).Conclusion Fer-rostatin-1 may alleviate retinal oxidative stress and the apoptosis of photoreceptor cells in RPD rats by inhibiting the Notch pathway,thereby mitigating retinal damage.

Objective To investigate the effects of the ferroptosis inhibitor Ferrostatin-1 on the apoptosis of photore-ceptor cells and the Notch pathway in rats with retinal photochemical damage(RPD).Methods Male Sprague-Dawley(SD)rats were randomly divided into the Control group(normally fed rats,intraperitoneal injection of an equal volume of saline),RPD group(RPD model rats,intraperitoneal injection of an equal volume of saline),Ferrostatin-1 group(RPD model rats,intraperitoneal injection of 5 mg·kg-1 Ferrostatin-1),and Ferrostatin-1+JFC group[RPD model rats,intrap-eritoneal injection of 5 mg·kg-1 Ferrostatin-1 and 0.5 mg·kg-1 Jagged1/FC chimeric protein(JFC,a Notch pathway acti-vator)],with 15 rats in each group.The retinal histopathology of rats in each group was evaluated via hematoxylin-eosin(HE)staining.The apoptosis of photoreceptor cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay.The expression level of ferrous ions(Fe2+),lactate dehydrogenase(LDH),malondialde-hyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in retinal tissues was measured using corresponding kits.Western blot was performed to assess the protein expression of transferrin receptor protein 1(TfR1),divalent metal transporter 1(DMT1),nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),recombinant glutathione peroxidase 4(GPX4),cleaved Caspase-3,Notch,and hairy and enhancer of split 1(Hes1).Results The thickness of the outer nuclear layer(ONL)in the Control group,RPD group,Ferrostatin-1 group,and Fer-rostatin-1+JFC group was(35.24±1.76)μm,(16.83±1.14)μm,(27.56±1.39)μm,and(21.48±1.23)μm,respec-tively;the apoptosis rate of photoreceptor cells in the four groups was(1.32±0.07)％,(18.57±1.63)％,(9.61±1.04)％,and(15.43±1.38)％,respectively.Compared with the Ferrostatin-1 group,the Ferrostatin-1+JFC group exhib-ited an aggravated retinal damage level,reduced ONL thickness,and increased apoptosis rate,and the differences were statistically significant(all P＜0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expres-sion level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the RPD group were higher than those in the Control group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Control group,and the differences were statistically significant(all P＜0.05).Compared with the RPD group,the Ferrostatin-1 group displayed a decrease in the expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 but an increase in the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4,and the differences were statistically significant(all P＜0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the Ferrostatin-1+JFC group were higher than those in the Ferrostatin-1 group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Ferrostatin-1 group,and the differences were statistically significant(all P＜0.05).Conclusion Fer-rostatin-1 may alleviate retinal oxidative stress and the apoptosis of photoreceptor cells in RPD rats by inhibiting the Notch pathway,thereby mitigating retinal damage.