Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model
<p>Abstract</p> <p>Background</p> <p>Inflammatory responses are detected in the retina of patients with age-related macular degeneration and <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice on rd8 background,(<it>Ccl2<su...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-03-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://www.jneuroinflammation.com/content/9/1/59 |
| _version_ | 1811246979577020416 |
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| author | Tuo Jingsheng Cao Xiaoguang Shen Defen Wang Yujuan Zhang Jun Oh Joo Prockop Darwin J Chan Chi-Chao |
| author_facet | Tuo Jingsheng Cao Xiaoguang Shen Defen Wang Yujuan Zhang Jun Oh Joo Prockop Darwin J Chan Chi-Chao |
| author_sort | Tuo Jingsheng |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Inflammatory responses are detected in the retina of patients with age-related macular degeneration and <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice on rd8 background,(<it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice) a model that develops progressive age-related macular degeneration-like retinal lesions including focal photoreceptor degeneration, abnormal retinal pigment epithelium and A2E accumulation. Tumor necrosis factor-inducible gene 6 protein is an anti-inflammatory protein and has been shown to improve myocardial infarction outcome and chemically injured cornea in mice by suppressing inflammation. In this study, we evaluated the effect of an intravitreous injection of recombinant TSG-6 on the retinal lesions of <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice.</p> <p>Methods</p> <p>Recombinant TSG-6 (400 ng) was administered by intravitreous injection into the right eye of six-week-old C<it>cl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice. Their left eye was injected with phosphate-buffered saline as a control. Funduscopic pictures were taken before injection and sequentially once a month after injection. The mice were killed two months after injection and the ocular histology examined. Retinal A2E, a major component of lipofuscin, was measured by high performance liquid chromatography. The microarray of ocular mRNA of 92 immunological genes was performed. The genes showing differentiated expression in microarray were further compared between the injected right eye and the contralateral (control) eye by [real-time quantitative reverse transcription polymerase chain reaction] qRT-PCR.</p> <p>Results</p> <p>The continuous monitoring of the fundus for two months showed a slower progression or alleviation of retinal lesions in the treated right eyes as compared with the untreated left eyes. Among 23 pairs of eyes, the lesion levels improved in 78.3%, stayed the same in 8.7% and progressed in 13.0%. Histology confirmed the clinical observation. Even though there was no difference in the level of A2E between the treated and the untreated eyes, microarray analysis of 92 immune genes showed that <it>IL-17a </it>was substantially decreased after the treatment. Expression of <it>TNF-α </it>showed a similar pattern to <it>IL-17a</it>. The results were consistent in duplicated arrays and confirmed by qRT-PCR.</p> <p>Conclusions</p> <p>We concluded that intravitreous administration of recombinant TSG-6 might stabilize retinal lesions in <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice on rd8 background. Modulation of ocular immunological gene expressions, especially IL-17a, could be one of the mechanisms.</p> |
| first_indexed | 2024-04-12T15:01:38Z |
| format | Article |
| id | doaj.art-e0454cf2691048beae5a8d1bea3c8226 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-12T15:01:38Z |
| publishDate | 2012-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-e0454cf2691048beae5a8d1bea3c82262022-12-22T03:28:04ZengBMCJournal of Neuroinflammation1742-20942012-03-01915910.1186/1742-2094-9-59Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine modelTuo JingshengCao XiaoguangShen DefenWang YujuanZhang JunOh JooProckop Darwin JChan Chi-Chao<p>Abstract</p> <p>Background</p> <p>Inflammatory responses are detected in the retina of patients with age-related macular degeneration and <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice on rd8 background,(<it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice) a model that develops progressive age-related macular degeneration-like retinal lesions including focal photoreceptor degeneration, abnormal retinal pigment epithelium and A2E accumulation. Tumor necrosis factor-inducible gene 6 protein is an anti-inflammatory protein and has been shown to improve myocardial infarction outcome and chemically injured cornea in mice by suppressing inflammation. In this study, we evaluated the effect of an intravitreous injection of recombinant TSG-6 on the retinal lesions of <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice.</p> <p>Methods</p> <p>Recombinant TSG-6 (400 ng) was administered by intravitreous injection into the right eye of six-week-old C<it>cl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice. Their left eye was injected with phosphate-buffered saline as a control. Funduscopic pictures were taken before injection and sequentially once a month after injection. The mice were killed two months after injection and the ocular histology examined. Retinal A2E, a major component of lipofuscin, was measured by high performance liquid chromatography. The microarray of ocular mRNA of 92 immunological genes was performed. The genes showing differentiated expression in microarray were further compared between the injected right eye and the contralateral (control) eye by [real-time quantitative reverse transcription polymerase chain reaction] qRT-PCR.</p> <p>Results</p> <p>The continuous monitoring of the fundus for two months showed a slower progression or alleviation of retinal lesions in the treated right eyes as compared with the untreated left eyes. Among 23 pairs of eyes, the lesion levels improved in 78.3%, stayed the same in 8.7% and progressed in 13.0%. Histology confirmed the clinical observation. Even though there was no difference in the level of A2E between the treated and the untreated eyes, microarray analysis of 92 immune genes showed that <it>IL-17a </it>was substantially decreased after the treatment. Expression of <it>TNF-α </it>showed a similar pattern to <it>IL-17a</it>. The results were consistent in duplicated arrays and confirmed by qRT-PCR.</p> <p>Conclusions</p> <p>We concluded that intravitreous administration of recombinant TSG-6 might stabilize retinal lesions in <it>Ccl2<sup>-/-</sup>/Cx3cr1<sup>-/- </sup></it>mice on rd8 background. Modulation of ocular immunological gene expressions, especially IL-17a, could be one of the mechanisms.</p>http://www.jneuroinflammation.com/content/9/1/59Age-related macular degenerationAnimal modelIL-17aTNF-αTSG-6Treatment |
| spellingShingle | Tuo Jingsheng Cao Xiaoguang Shen Defen Wang Yujuan Zhang Jun Oh Joo Prockop Darwin J Chan Chi-Chao Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model Journal of Neuroinflammation Age-related macular degeneration Animal model IL-17a TNF-α TSG-6 Treatment |
| title | Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model |
| title_full | Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model |
| title_fullStr | Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model |
| title_full_unstemmed | Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model |
| title_short | Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model |
| title_sort | anti inflammatory recombinant tsg 6 stabilizes the progression of focal retinal degeneration in a murine model |
| topic | Age-related macular degeneration Animal model IL-17a TNF-α TSG-6 Treatment |
| url | http://www.jneuroinflammation.com/content/9/1/59 |
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