Abstract
BackgroundInflammatory responses are detected in the retina of patients with age-related macular degeneration and Ccl2-/-/Cx3cr1-/- mice on rd8 background,(Ccl2-/-/Cx3cr1-/- 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 Ccl2-/-/Cx3cr1-/- mice.MethodsRecombinant TSG-6 (400 ng) was administered by intravitreous injection into the right eye of six-week-old Ccl2-/-/Cx3cr1-/- 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.ResultsThe 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 IL-17a was substantially decreased after the treatment. Expression of TNF-α showed a similar pattern to IL-17a. The results were consistent in duplicated arrays and confirmed by qRT-PCR.ConclusionsWe concluded that intravitreous administration of recombinant TSG-6 might stabilize retinal lesions in Ccl2-/-/Cx3cr1-/- mice on rd8 background. Modulation of ocular immunological gene expressions, especially IL-17a, could be one of the mechanisms.
Highlights
Inflammatory responses are detected in the retina of patients with age-related macular degeneration and Ccl2-/-/Cx3cr1-/- mice on rd8 background,(Ccl2-/-/Cx3cr1-/- mice) a model that develops progressive age-related macular degeneration-like retinal lesions including focal photoreceptor degeneration, abnormal retinal pigment epithelium and A2E accumulation
We reported that the subretinal injection of an adeno-associated virus vector in which a portion of the soluble vascular endothelial growth factor (VEGF) receptor gene was cloned to trap excess VEGF-A either stabilizes or arrests the progression of retinal lesions in Ccl2-/-/Cx3cr1-/- mice [7]
We found that intravitreous delivery of recombinant Tumor necrosis factor-inducible gene 6 protein (TSG-6) protein could stabilize the progression of retinal lesions in Ccl2-/-/Cx3cr1-/- mice on rd8 background, Figure 5 Gene expression array in the retina
Summary
Inflammatory responses are detected in the retina of patients with age-related macular degeneration and Ccl2-/-/Cx3cr1-/- mice on rd background,(Ccl2-/-/Cx3cr1-/- 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. The pathological features of this neurodegenerative disease include degeneration and atrophy of the photoreceptors and the retinal pigment epithelium (RPE) in the macula. The advanced stage of AMD presents as the exudative/neovascular or ‘wet’ form with choroidal neovascularization, and the geographic atrophy or ‘dry’ form with loss of the photoreceptors and RPE. Except for the suppression of choroidal neovascularization, there are few options for AMD intervention. Body mass reduction, and specific vitamins and nutrient supplements have been reported to slow disease progression [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
