Protection of Retina by αB Crystallin in Sodium Iodate Induced Retinal Degeneration

Zhou, Peng; Kannan, Ram; Spee, Christine; Sreekumar, Parameswaran G.; Dou, Guo‐Rui; Hinton, David R.

doi:10.1371/journal.pone.0098275

Cited by 58 publications

(66 citation statements)

References 51 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent study showed that Crystallins may play a critical role in the protection against oxidative stress and retinal degeneration [46]. In our study we were similarly able to observe the involvement of Gamma-crystallin D in retinal structural changes induced by UVA and UVB.…”

Section: Discussionsupporting

confidence: 82%

UV-induced retinal proteome changes in the rat model of age-related macular degeneration

Pavelić

Klobučar

Sedić

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is characterized by irreversible damage of photoreceptors in the central posterior part of the retina, called the macula and is the most common cause of vision loss in those aged over 50. A growing body of evidence shows that cumulative long-term exposure to UV radiation may be harmful to the retina and possibly leads to AMD irrespective of age. In spite of many research efforts, cellular and molecular mechanisms leading to UV-induced retinal damage and possibly retinal diseases such as AMD are not completely understood. In the present study we explored damage mechanisms accounting for UV-induced retinal phototoxicity in the rats exposed to UVA and UVB irradiation using a proteomics approach. Our study showed that UV irradiation induces profound changes in the retinal proteomes of the rats associated with the disruption of energy homeostasis, oxidative stress, DNA damage response and structural and functional impairments of the interphotoreceptor matrix components and their cell surface receptors such as galectins. Two small leucine-rich proteoglycans, biglycan and lumican, were identified as phototoxicity biomarkers associated with UV-induced disruption of interphotoreceptor matrix (IPM). In addition, UVB induced activation of Src kinase, which could account for cytoskeletal rearrangements in the retina was observed at the proteomics level. Pharmacological intervention either to target Src kinase with the aim of preventing cytoskeletal rearrangements in the retinal pigment epithelium (RPE) and neuronal retina or to help rebuild damaged IPM may provide fresh avenues of treatment for patients suffering from AMD.

show abstract

Section: Discussionsupporting

confidence: 82%

UV-induced retinal proteome changes in the rat model of age-related macular degeneration

Pavelić

Klobučar

Sedić

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

show abstract

“…This notion is reinforced by the fact that silencing of αBC exacerbates oxidative stress. whereas the over-expression has the opposite effect [33]. In the present study, we have shown that αBC treatment enhances retinal SOD activity and reduces MDA concentration in MNU administered mice.…”

Section: Discussionsupporting

confidence: 52%

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

“…17 After a 48-hour incubation in medium with or without recombinant TGF-b2 or BMP4, total cell lysates were extracted with lysis buffer. In separate experiments, empty vector or aB-crystallin transfected cells were treated with 10 ng TGF-b2 for 2 hours and nuclear and cytosolic fractions were separated.…”

Section: Western Blot Analysismentioning

confidence: 99%

αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition

Ishikawa

Sreekumar

Spee

et al. 2016

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Subretinal fibrosis is an end stage of neovascular age-related macular degeneration, characterized by fibrous membrane formation after choroidal neovascularization. An initial step of the pathogenesis is an epithelial-mesenchymal transition (EMT) of retinal pigment epithelium cells. aB-crystallin plays multiple roles in age-related macular degeneration, including cytoprotection and angiogenesis. However, the role of aB-crystallin in subretinal EMT and fibrosis is unknown. Herein, we showed attenuation of subretinal fibrosis after regression of laser-induced choroidal neovascularization and a decrease in mesenchymal retinal pigment epithelium cells in aB-crystallin knockout mice compared with wild-type mice. aB-crystallin was prominently expressed in subretinal fibrotic lesions in mice. In vitro, overexpression of aB-crystallin induced EMT, whereas suppression of aB-crystallin induced a mesenchymal-epithelial transition. Transforming growth factor-b2einduced EMT was further enhanced by overexpression of aB-crystallin but was inhibited by suppression of aB-crystallin. Silencing of aB-crystallin inhibited multiple fibrotic processes, including cell proliferation, migration, and fibronectin production. Bone morphogenetic protein 4 upregulated aB-crystallin, and its EMT induction was inhibited by knockdown of aB-crystallin. Furthermore, inhibition of aB-crystallin enhanced monotetraubiquitination of SMAD4, which can impair its nuclear localization. Overexpression of aB-crystallin enhanced nuclear translocation and accumulation of SMAD4 and SMAD5. Thus, aB-crystallin is an important regulator of EMT, acting as a molecular chaperone for SMAD4 and as its potential therapeutic target for preventing subretinal fibrosis development in neovascular age-related macular degeneration. (Am J Pathol 2016, 186: 859e873; http:// dx

show abstract

Protection of Retina by αB Crystallin in Sodium Iodate Induced Retinal Degeneration

Cited by 58 publications

References 51 publications

UV-induced retinal proteome changes in the rat model of age-related macular degeneration

UV-induced retinal proteome changes in the rat model 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

αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition

Contact Info

Product

Resources

About