Protective Effect of Mitochondrially Targeted Peptide Against Oxidant Injury of Cone Photoreceptors Through Preventing Necroptosis Pathway.

Abstract

Retinopathy is an eye disease caused by the death of retinal cells in the macular area and the surrounding choroid. As the retinal rod cell dysfunction and death lead to the loss of night vision, the disease will lead to visual dysfunction and blindness as the disease progresses. Because of the irreversible nature of cell death, gene therapy has become a research hotspot in the field of retinopathy. But the technology is still in animal studies or clinical trials, and more research is needed to prove its feasibility. In this study, oxidative damage cell model was established and divided into a control group, H₂O₂ group, SS31 +NEC1 group, SS31 +H₂O₂ group, and SS31 +NEC1 +H₂O₂ group, for different interventions. The cell survival rate of the H₂O₂ group was significantly increased compared with those of the SS31 + H₂O₂ group, SS31 +NEC1 +H₂O₂ group, and NEC1 +H₂O₂ group. Nec1 combined treatment significantly reduced reactive oxygen species (ROS) production compared with that in the H₂O₂ group. The level of MDA in the SS31 group, Nec-1 group and combined treatment of SS31 +NEC1 group decreased significantly compared with the H₂O₂ group. The proportion of cells with decreased mitochondrial membrane potential in the H₂O₂ group significantly increased, and the rate of positivity for propidium iodide (PI) of 661W cells in the H₂O₂ group and the control group significantly increased. Nine hours after H₂O₂ treatment of 661W cells, the RIP3 expression level began to increase, and peaked at 24 h. The level of RIP3 in the H₂O₂ group was significantly increased, while this level was downregulated in the SS31 and NEC1 treatment groups. Therefore, this study suggests that SS31 has a partial protective effect on 661W cells by inhibiting necrosis, which has certain guiding significance for the treatment of retinal diseases.

• Authors: Yuan He, Yun Xu, Zejun Chen, Beilei He, Zhuoya Quan, Ruixue Zhang, Yuan Ren
• Journal: Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 17 Issue 2 Pg. 279-290 (Feb 28 2021) ISSN: 1550-7033 [Print] United States
• PMID: 33785098 (Publication Type: Journal Article)

Chemical References

• Oligopeptides
• Oxidants
• Peptides
• Reactive Oxygen Species
• Hydrogen Peroxide

Topics

• Animals
• Apoptosis
• Hydrogen Peroxide (toxicity)
• Mitochondria
• Necroptosis
• Oligopeptides (metabolism, pharmacology)
• Oxidants (metabolism, pharmacology)
• Oxidative Stress
• Peptides (pharmacology)
• Reactive Oxygen Species (metabolism)
• Retinal Cone Photoreceptor Cells