Identification of crystallin family proteins in vitreous body in rat endotoxin‐induced uveitis: Involvement of crystallin truncation in uveitis pathogenesis

Bahk, Song-Chul; Lee, Sook-Hee; Jang, Jung-Un; Choi, Chang-Uk; Lee, Bok-Soo; Chae, Soo-Cheon; Song, Hye-Jin; Park, Chul–Seung; Yang, Yun-Sik; Chung, Hun‐Taeg

doi:10.1002/pmic.200500779

Cited by 19 publications

(21 citation statements)

References 29 publications

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“…Crystallins are chaperone proteins expressed in many tissues[30,31], and were present in both the retina and vitreous. The top 20 retina proteins contained fifteen different crystallins, which are upregulated in the retina during the progression of ocular diseases, including uveitis[30,32,33]. Thus, multiple cells and tissues, including those outside the eye, may contribute to the vitreous proteome.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Interactions in the Mouse Vitreous-Retina Complex

Skeie

Mahajan

2013

PLoS ONE

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PurposeHuman vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina. MethodsVitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software. ResultsWe identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor. ConclusionsOur analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.

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Section: Discussionmentioning

confidence: 99%

Proteomic Interactions in the Mouse Vitreous-Retina Complex

Skeie

Mahajan

2013

PLoS ONE

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“…To characterize the mechanism of EIU, Bahk et al analysed the infiltration of proteins in the vitreous bodies of rats with EIU and normal rats using 2-DE-MALDI-TOF/MS and micro LC/LC-MS/MS, identifying specific modifications in the crystallin family proteins [50]. …”

Section: Future Perspectives: Proteomics For Intravitreal Inflammamentioning

confidence: 99%

Proteomic Analyses of the Vitreous Humour

Angi

Kalirai

Coupland

et al. 2012

Mediators of Inflammation

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The human vitreous humour (VH) is a transparent, highly hydrated gel, which occupies the posterior segment of the eye between the lens and the retina. Physiological and pathological conditions of the retina are reflected in the protein composition of the VH, which can be sampled as part of routine surgical procedures. Historically, many studies have investigated levels of individual proteins in VH from healthy and diseased eyes. In the last decade, proteomics analyses have been performed to characterise the proteome of the human VH and explore networks of functionally related proteins, providing insight into the aetiology of diabetic retinopathy and proliferative vitreoretinopathy. Recent proteomic studies on the VH from animal models of autoimmune uveitis have identified new signalling pathways associated to autoimmune triggers and intravitreal inflammation. This paper aims to guide biological scientists through the different proteomic techniques that have been used to analyse the VH and present future perspectives for the study of intravitreal inflammation using proteomic analyses.

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“…In our previous studies, crystallins (the major proteins of the vitreous body) were induced in response to ocular inflammations of animal uveitis models. These findings suggested that post-translational truncations of αA- and αB-crystallins, phosphorylation of αB-crystallin, and new production of βA4- and βB2-crystallins are intercorrelated with uveitis progression and inflammatory responses [13,14]. The regulatory mechanism of the phosphorylation of αB-crystallin [29] results in the inhibition of RAS [23].…”

Section: Discussionmentioning

confidence: 99%

“…During ischemic preconditioning, the bovine B2 chain of α-crystallin is activated through the phosphorylation of the serine residues (Ser-45 and Ser-59) mediated by ERK1/2 and p38, respectively, thereby acting as an effector protein [8-12]. More recently, post-translational modifications of mouse αA-crystallin have been reported [13,14]. The N-terminal acetylation and the variable C-terminal truncation of αA-crystallin are regarded as important modifications for the activation of crystallin proteins [15].…”

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confidence: 99%

A Potential Role of Crystallin in the Vitreous Bodies of Rats after Ischemia-reperfusion Injury

Hong

Yang

2012

Korean J Ophthalmol

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PurposeIschemia-reperfusion injury (I/R injury) is known not only to induce hypoxic and oxidative stress, but also to cause retinal degeneration in rats. Crystallins, known to inhibit the formation of reactive oxygen species, reduce apoptotic cell death. Our goal was to clarify not only the role of I/R injury-mediated crystallins, but also to evaluate the correlation of these compounds to anti-inflammation in the vitreous body.MethodsTwenty-four Sprague-Dawley rats were used in this study. We induced I/R injury by clamping the optic nerve for 30 minutes and then releasing it. The vitreous bodies were obtained from the experimental and control subjects 24, 48, and 72 hours after I/R injury. Two-dimensional electrophoresis was performed, and the targeted spots were further investigated using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, spectrophotometry, Western blotting, and histological examination.ResultsAfter I/R injury, 23 spots were identified as crystallins. The βB2 crystallins were transcriptionally and post-translationally regulated, whereas the αB crystallins were controlled by post-translational modifications in the vitreous bodies of the rats. The total amounts of αA and β crystallins (including isotypes of β crystalline) had increased 48 hours after injury. The phosphorylation of αB crystallin (at serine residues 19, 45, and 59) was significantly increased 48 hours later, whereas phosphorylation of ERK1/2 showed the greatest decrease.ConclusionsDuring hypoxic and oxidation stress, our results suggest that phosphorylated αB crystalline inhibits RAS, resulting in the inactivation of ERK1/2. The phosphorylation of αB crystallin may be associated with the inflammatory suppression in the vitreous body via the I/R injury model system.

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Identification of crystallin family proteins in vitreous body in rat endotoxin‐induced uveitis: Involvement of crystallin truncation in uveitis pathogenesis

Cited by 19 publications

References 29 publications

Proteomic Interactions in the Mouse Vitreous-Retina Complex

Proteomic Interactions in the Mouse Vitreous-Retina Complex

Proteomic Analyses of the Vitreous Humour

A Potential Role of Crystallin in the Vitreous Bodies of Rats after Ischemia-reperfusion Injury

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