Dataset Information

Protection of retina by ?B crystallin in sodium iodate induced retinal degeneration.

ABSTRACT: Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD and ?B crystallin expression is increased in RPE and associated drusen in AMD. The purpose of this study was to investigate the role of ?B crystallin in sodium iodate (NaIO3)-induced retinal degeneration, a model of AMD in which the primary site of pathology is the RPE. Dose dependent effects of intravenous NaIO3 (20-70 mg/kg) on development of retinal degeneration (fundus photography) and RPE and retinal neuronal loss (histology) were determined in wild type and ?B crystallin knockout mice. Absence of ?B crystallin augmented retinal degeneration in low dose (20 mg/kg) NaIO3-treated mice and increased retinal cell apoptosis which was mainly localized to the RPE layer. Generation of reactive oxygen species (ROS) was observed with NaIO3 in mouse and human RPE which increased further after ?B crystallin knockout or siRNA knockdown, respectively. NaIO3 upregulated AKT phosphorylation and peroxisome proliferator-activator receptor-? (PPAR?) which was suppressed after ?B crystallin siRNA knockdown. Further, PPAR? ligand inhibited NaIO3-induced ROS generation. Our data suggest that ?B crystallin plays a critical role in protection of NaIO3-induced oxidative stress and retinal degeneration in part through upregulation of AKT phosphorylation and PPAR? expression.

SUBMITTER: Zhou P

PROVIDER: S-EPMC4038555 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Protection of retina by αB crystallin in sodium iodate induced retinal degeneration.

Zhou Peng P Kannan Ram R Spee Christine C Sreekumar Parameswaran G PG Dou Guorui G Hinton David R DR

PloS one 20140529 5

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD and αB crystallin expression is increased in RPE and associated drusen in AMD. The purpose of this study was to investigate the role of αB crystallin in sodium iodate (NaIO3)-induced retinal degeneration, a model of AMD in which the primary site of pathology is the RPE. Dose dependent effects of intravenous NaIO3 (20-70 mg/kg) ...[more]

PMID: 24874187

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Project description:BackgroundSodium iodate (SI) is a chemical widely applied to induce retina degeneration in animal models. SI treatment caused formation of rosettes/folds in the outer nuclear layer (ONL) of the rat retina, but it was previously unclear whether SI also forms rosettes in mice. In addition, SI induced retina degeneration was never addressed in non-separate sclerochoroid/retina pigment epithelium/retina whole mount. Here we displayed features of retina degeneration including rosette formation in mice and developed a morphological analytic assessment using sclerochoroid/retina pigment epithelium/retina whole mounts.MethodsSI was intraperitoneally injected in Sprague-Dawley (SD) rats and C57BL/6J mice using a single dose (50 mg/kg) or with a dose range (10 to 50 mg/kg) in BALB/C mice. Rat retinas were investigated up to 2-week post-injection by histology and whole mounts, and mouse retinas were investigated up to 3-week post-injection by histology, fluorescent staining of sections and/or sclerochoroid/retina pigment epithelium/retina whole mounts for the morphological evaluations of the SI-induced retina damage.ResultsSI-induced retina damage caused photoreceptor (PR) degeneration and rosettes/folds formation, as well as retina pigment epithelium degeneration and inward migration. It displayed mixed nuclei from choroid to PRs, due to layer disorganization, as shown by single horizontal images in the sclerochoroid/retina pigment epithelium/retina whole mounts. Measurement of the PR rosette area induced by SI provided a quantitative, morphological evaluation of retina degeneration.ConclusionsThe method of non-separate sclerochoroid/retina pigment epithelium/retina whole staining and mount allows us to observe the integral horizontal view of damage from sclera to PR layers, which cannot be addressed by using sectioned and separate whole mount methods. This method is applicable for morphological evaluation of retina damage, especially in the subretinal layer.

Project description:BackgroundAge-related macular degeneration (AMD) is one of the major causes of blindness in the elderly over the age of 60. AMD is divided into dry AMD and wet AMD. Although there are certain treatment methods for wet age-related macular degeneration (AMD), there are no effective treatments for dry AMD yet, and finding new drugs or treatment methods for dry AMD has become a priority. For this purpose, this study explored Glabridin (Glab), an isoflavane found in the root extract of licorice, which has never been investigated in relation to eye diseases.PurposeTo investigate the effect of Glab on the sodium iodate (NaIO3) induced retinal degeneration in vitro and in vivo.MethodsIn vitro, cell viability and cytotoxicity were tested with methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay among the groups of ARPE-19 cells. The cell apoptosis was tested with Hoechst 33342 staining and flow cytometry. The level of Reactive oxygen species (ROS) was measured to check the effect on oxidative stress. The protein expressions of phosphorylation of ERK1/2 and p38 were detected by Western blotting. In vivo, C57BL/6J mice were pretreated with Glab intraperitoneally for one week and continued for 4 weeks. NaIO3 was given to mice through tail vein intravenous injection after 1 week of Glab administration. The retinas of mice were monitored by Optical coherence tomography (OCT) and electroretinography (ERG) at 1w, 2w, 3w, and 4w, respectively, followed by H&E staining.ResultsIn vitro, the Glab protected the retinal pigment epithelial (RPE) cells against oxidative stress and apoptosis by inhibiting phosphorylation of ERK1/2 and the p38 MAPK pathway. In vivo, Glab significantly prevented retinal damage by stopping the progression of retinal degeneration and reducing the formation of deposits on the RPE layer induced by NaIO3. According to the findings of electroretinogram (ERG), Glab helped to maintain the normal function of the retina.ConclusionGlabridin has a protective effect against retinal degeneration. It is suggested that Glab be further investigated for the treatment of retinal degeneration diseases.

Dataset Information

Protection of retina by ?B crystallin in sodium iodate induced retinal degeneration.

Publications

Protection of retina by αB crystallin in sodium iodate induced retinal degeneration.

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