Protection of Retina by Mini-αA in NaIO3-Induced Retinal Pigment Epithelium Degeneration Mice

Zhang, Jinglin; Zhao, Xiujuan; Cai, Yu; Li, Yonghao; Yu, Xiling; Lü, Lin

doi:10.3390/ijms16011644

Cited by 23 publications

(23 citation statements)

References 29 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7B). Our results is coherent to the 24-hour, 3.5 mM sodium iodate treatment, which LC3B-II expression is increased in ARPE-19 cells28. Similarly, 1 and 3-day hydrogen peroxide treatments also increase the autophagic activity in ARPE-19 cells, but reduces in the 14-day treatment19.…”

Section: Discussionsupporting

confidence: 88%

“…6). Increased expression of other unfolded protein response pathways, such as CHOP and XBP1, has also been reported in RPE cells with acute sodium iodate treatment28. These indicates that sodium iodate would induce ER stress in RPE cells.…”

Section: Discussionmentioning

confidence: 71%

“…Sodium iodate-induced RPE cell death could be related to the upregulation of genes in the cell death, apoptosis and acute response to stress pathways24. Moreover, the increased expressions of inflammation-related proteins (complement factor C3 and calcium-independent phospholipase A2)252627, pro-angiogenic factor (IL-8)14, chemoattractant (stromal cell-derived factor-1)25, oxidative stress-related gene (heme oxygenase)26 as well as apoptotic marker (caspase-3)28 have been reported. Apart from induction of RPE cell death, sodium iodate would also cause mitochondrial dysfunction and impairment of glycolysis1629.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Continuous exposure to non-lethal doses of sodium iodate induces retinal pigment epithelial cell dysfunction

Zhang

Brelén

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Age-related macular degeneration (AMD), characterized by progressive degeneration of retinal pigment epithelium (RPE), is the major cause of irreversible blindness and visual impairment in elderly population. We previously established a RPE degeneration model using an acute high dose sodium iodate to induce oxidative stress. Here we report findings on a prolonged treatment of low doses of sodium iodate on human RPE cells (ARPE-19). RPE cells were treated continuously with low doses (2–10 mM) of sodium iodate for 5 days. Low doses (2–5 mM) of sodium iodate did not reduce RPE cell viability, which is contrasting to cell apoptosis in 10 mM treatment. These low doses are sufficient to retard RPE cell migration and reduced expression of cell junction protein ZO-1. Phagocytotic activity of RPE cells was attenuated by sodium iodate dose-dependently. Sodium iodate also increased expression of FGF-2, but suppressed expression of IL-8, PDGF, TIMP-2 and VEGF. Furthermore, HTRA1 and epithelial-to-mesenchymal transition marker proteins were downregulated, whereas PERK and LC3B-II proteins were upregulated after sodium iodate treatment. These results suggested that prolonged exposure to non-lethal doses of oxidative stress induces RPE cell dysfunctions that resemble conditions in AMD. This model can be used for future drug/treatment investigation on AMD.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Continuous exposure to non-lethal doses of sodium iodate induces retinal pigment epithelial cell dysfunction

Zhang

Brelén

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The antiapoptotic and/or anti-inflammatory effects of recombinant human αA or αB crystallin were successfully demonstrated in several animal disease models such as experimental cataracts, experimental autoimmune encephalomyelitis (EAE), stroke, cardiac ischemia-reperfusion, optic neuropathy, experimental autoimmune uveitis (EAU), and retinal degeneration [74-79]. Work from the laboratories of Sharma and Clark have identified several short chain peptides of αA and αB crystallin that elicit chaperone properties [80-82].…”

Section: α-Crystallin and Its Constitutive Peptides As Therapeutic Momentioning

confidence: 99%

Alpha crystallins in the retinal pigment epithelium and implications for the pathogenesis and treatment of age-related macular degeneration

Kannan

Sreekumar

Hinton

2016

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Background αA- and αB crystallins are principal members of the small heat shock protein family and elicit both a cell protective function and a chaperone function. α-Crystallins have been found to be prominent proteins in normal and pathological retina emphasizing the importance for in-depth understanding of their function and significance. Scope of Review Retinal pigment epithelial cells (RPE) play a vital role in the pathogenesis of age-related macular degeneration (AMD). This review addresses a number of cellular functions mediated by α-crystallins in the retina. Prominent expression of αB crystallin in mitochondria may serve to protect cells from oxidative injury. αB crystallin as secretory protein via exosomes can offer neuroprotection to adjacent RPE cells and photoreceptors. The availability of chaperone-containing minipeptides of αB crystallin could prove to be a valuable new tool for therapeutic treatment of retinal disorders. Major Conclusions α-Crystallins are expressed in cytosol and mitochondria of RPE cells and are regulated during oxygen-induced retinopathy and during development. α-Crystallins protect RPE from oxidative-and ER stress-induced injury and autophagy. αB-Crystallin is a modulator of angiogenesis and vascular endothelial growth factor. αB Crystallin is secreted via exosomal pathway. Minichaperone peptides derived from αB Crystallin prevent oxidant induced cell death and have therapeutic potential. General Significance Overall, this review summarizes several novel properties of α-crystallins and their relevance to maintaining normal retinal function. In particular, the use of α-crystallin derived peptides is a promising therapeutic strategy to combat retinal diseases such as AMD.

show abstract

“…Theses adaptive activities provide a primary defense against undesirable outcomes of cellular stress, highlighting the possibility that αBC might be used therapeutically [29,30]. To date, the αBC induced protection has been demonstrated in various cell cultures including RPE cells, astrocytes, endothelial cells, and pericytes [31]. A pioneering therapeutic study showed that intravitreal delivered β-crystallins or γ-crystallins exerted nutritional effects on the RGCs after optic nerve crush.…”

Section: Discussionmentioning

confidence: 99%

Intravitreous Delivery of Αb-Crystallin Ameliorates N-Methyl-N-Nitrosourea Induced Photoreceptor Degeneration in Mice: An in vivo and ex vivo Study

Tao

Ding

Yao³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: αB –crystallin (αBC) belongs to the family of small heat shock proteins that are necessary for maintaining oxygen homeostasis. This study was designed to explore the possible effects of αBC on N-methyl- N-nitrosourea (MNU) induced retinal degeneration and the underlying mechanisms. Methods: The αBC was injected into the vitreous bodies of MNU administered mice. The retinal morphology and visual function of experimental animals were analyzed by electroretinography (ERG), Spectral domain optical coherence tomography (SD-OCT), fundus photographs, optokinetic testing and immunohistochemistry assay. Results: Optokinetic behavioural tests and ERG examination suggested that the visual impairments of the MNU administered mice were ameliorated effectively by αBC treatment. OCT analysis showed that the major retinal architecture of the MNU administered mice was efficiently rescued by αBC treatment. Fundus examination suggested that the lesion size of the MNU administered mice was decreased by αBC treatment. MNU induced photoreceptor loss was also mitigated by αBC treatment as shown by hematoxylin and eosin staining. In particular, the immunostaining study suggested that M-cone photoreceptors, rather than the S-cone photoreceptors, were preferentially rescued, indicating that the photoreceptor populations have different sensitivities to αBC. The mechanism study suggested that the anti-apoptotic, anti-oxidative and neurotrophic function of αBC collectively contributed to these therapeutic effects. Conclusion: Intravitreal delivery of αBC could alleviate MNU induced photoreceptor degeneration and visual impairment. Further refinement of the αBC induced protection would afford a novel therapeutic strategy for retinitis pigmentosa.

show abstract

Protection of Retina by Mini-αA in NaIO3-Induced Retinal Pigment Epithelium Degeneration Mice

Cited by 23 publications

References 29 publications

Continuous exposure to non-lethal doses of sodium iodate induces retinal pigment epithelial cell dysfunction

Continuous exposure to non-lethal doses of sodium iodate induces retinal pigment epithelial cell dysfunction

Alpha crystallins in the retinal pigment epithelium and implications for the pathogenesis and treatment of age-related macular degeneration

Intravitreous Delivery of Αb-Crystallin Ameliorates N-Methyl-N-Nitrosourea Induced Photoreceptor Degeneration in Mice: An in vivo and ex vivo Study

Contact Info

Product

Resources

About