Inhibition of LOX-1 prevents inflammation and photoreceptor cell death in retinal degeneration

Gao, Xinran; Zhu, Ruilin; Du, Jiantong; Zhang, Wenbo; Gao, Wen; Yang, Liu

doi:10.1016/j.intimp.2020.106190

Cited by 8 publications

(8 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in the studies of Gao et al [22] and Mandal et al [23] light induced increased NF-κB protein expression in photoreceptor cells. We noted that BALB/C mice were exposed to 15000 lux cold light for 4 h or that 661W cells were exposed to 1000 lux cold light for 5 ~ 7 d. It is possible that excessive light stimulation at a high intensity or over a long period of time is more likely to cause photoreceptor cells to damage the in ammatory response rather than undergo apoptosis, resulting in increased expression of NF-κB protein that is sensitive to in ammatory stimulation.…”

Section: Delphinidin Regulates the Expression Of Key Factors In The N...mentioning

confidence: 87%

Delphinidin regulates the NF-κB/AP-1/caspase-3 pathway to protect against apoptosis of retinal photoreceptors under conditions of photochemical damage

Deng

et al. 2022

Preprint

View full text Add to dashboard Cite

Retinal photochemical damage (RPD) can be the main cause of various ophthalmic diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Patients' vision can be severely impaired in the late stages of these eye diseases. Delphinidin, one of the major functional components of anthocyanins, has shown preventive effects on RPD and ophthalmic diseases induced by RPD, but the underlying mechanisms are complex and unclear. This study investigated the protective effect of delphinidin on photochemically damaged retinal photoreceptors in vivo and in vitro and characterized the underlying mechanisms. In vivo experiments showed that delphinidin downregulated the expression levels of caspase-3, and reduced the apoptosis rate of retinal photoreceptor cells in SD rats, thus protecting the structural integrity of the retina. In vitro experiments showed that delphinidin could maintain the normal ultrastructure of the mitochondrial endoplasmic reticulum membrane, reduce the apoptosis rate caused by light injury and improve the survival rate of light-damaged 661W cells. In addition, we found that delphinidin increased the mRNA and activated protein expression of NF-κB p65, NF-κB p50, and IκBα in photochemically injured 661W cells, and decreased the mRNA and protein expression of AP-1 (c-fos/c-jun) and Caspase-3/-8/-9. Compared with the model group, phospho-NF-κB p65 in delphinidin-treated cells was translocated into the nucleus, and the nuclear phospho-NF-κB p65 expression was increased, while nuclear c-jun expression was decreased. These results suggested that delphinidin resisted RPD-induced apoptosis of retinal photoreceptors by regulating the expression of factors involved in the NF-κB/AP-1/caspase-3 pathway.

show abstract

Section: Delphinidin Regulates the Expression Of Key Factors In The N...mentioning

confidence: 87%

Delphinidin regulates the NF-κB/AP-1/caspase-3 pathway to protect against apoptosis of retinal photoreceptors under conditions of photochemical damage

Deng

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The cells of the retinal neuroepithelial layer are terminally differentiated neurons, with no regenerative ability. Noninfective inflammation plays an important role in retinal degeneration, such as the loss of retinal ganglion cells in glaucoma [ 28 ], the apoptosis of pigment epithelium cells in retinitis pigmentosa [ 29 ], the dysfunction of retinal photoreceptor cells in age-related macular degeneration [ 30 ], and even retinal detachment [ 31 ]. However, the exact mechanism of noninfectious inflammatory activation in the retina was still unclear.…”

Section: Discussionmentioning

confidence: 99%

Intravitreal injection of mitochondrial DNA induces cell damage and retinal dysfunction in rats

Guo

Gan

et al. 2022

Biol Res

View full text Add to dashboard Cite

Background Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo. Methods Retinal injury was induced with white light or intravitreal injection of lipopolysaccharide (LPS). After light- or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluate the activation of cGAS-STING pathway and the levels of apoptosis-associated protein at different times after mtDNA injection. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function. Results Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-β mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-β were upregulated. mtDNA injection also induced the activation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA injection. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA injection. Conclusions Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.

show abstract

“…The cells of the retinal neuroepithelial layer are terminally differentiated neurons, with no regenerative ability. Injuries such as infection, ischemia, and trauma in retinal neuroepithelial layer cells can lead to visual impairment and even blindness [21]. Some retinal degenerative diseases involve progressive photoreceptor cell loss and the degradation of RPE cells [22].…”

Section: Discussionmentioning

confidence: 99%

“…In ammation is a plausible link between mitochondrial damage and retinal disease. Research has demonstrated that the activation of retinal in ammation induces cell damage, such as the loss of retinal ganglion cells in glaucoma[28], the apoptosis of pigment epithelium cells in retinitis pigmentosa [26], the dysfunction of retinal photoreceptor cells in age-related macular degeneration [21], and even retinal detachment [29], which can progress and induce an in ammatory response, resulting in retinal atrophy. After cellular stress or tissue injury, cells release intracellular molecules into the extracellular space, which trigger the stress signals called DAMPs.…”

Section: Discussionmentioning

confidence: 99%

Intravitreal Injection of Mitochondrial DNA Induces Cell Damage and Retinal Dysfunction in Rats

Guo

Gan

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo.Methods: Retinal injury was induced by white light or intravitreal injection of lipopolysaccharide (LPS). After light- or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluated the activation of cGAS-STING pathway and the levels of apoptosis-associated protein at different times after mtDNA stimulation. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function.Results: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-β mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-β were upregulated. mtDNA stimulation also induced the phosphorylation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA stimulation. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA stimulation.Conclusion: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.

show abstract

Inhibition of LOX-1 prevents inflammation and photoreceptor cell death in retinal degeneration

Cited by 8 publications

References 41 publications

Delphinidin regulates the NF-κB/AP-1/caspase-3 pathway to protect against apoptosis of retinal photoreceptors under conditions of photochemical damage

Delphinidin regulates the NF-κB/AP-1/caspase-3 pathway to protect against apoptosis of retinal photoreceptors under conditions of photochemical damage

Intravitreal injection of mitochondrial DNA induces cell damage and retinal dysfunction in rats

Intravitreal Injection of Mitochondrial DNA Induces Cell Damage and Retinal Dysfunction in Rats

Contact Info

Product

Resources

About