Dataset Information

Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice.

ABSTRACT: We generated a mouse model (cKO) with a conditional deletion of TGF-beta signaling in the retinal neurons by crossing TGF-beta receptor I (TGF-beta RI) floxed mice with nestin-Cre mice. Almost all of the newborn cKO mice had retinal detachment at the retinal pigment epithelium (RPE)/photoreceptor layer junction of the neurosensory retina (NSR). The immunostaining for chondroitin-6-sulfate showed a very weak reaction in cKO mice in contrast to intense staining in the photoreceptor layer in wild-type mice. Macroscopic cataracts, in one or both eyes, were observed in 50% of the mice by 6 months of age, starting as early as the first month after birth. The cKO mouse model demonstrates that the TGF-beta signaling deficiency in retinal cells leads to decreased levels of chondroitin sulfate proteoglycan in the retinal interphotoreceptor matrix. This in turn causes retinal detachment due to the loss of adhesion of the NSR to RPE.

SUBMITTER: Honjo Y

PROVIDER: S-EPMC2062516 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice.

Honjo Yasuyuki Y Nagineni Chandrasekharam N CN Larsson Jonas J Nandula Seshagiri R SR Hooks John J JJ Chan Chi-Chao CC Karlsson Stefan S Kulkarni Ashok B AB

Biochemical and biophysical research communications 20061116 2

We generated a mouse model (cKO) with a conditional deletion of TGF-beta signaling in the retinal neurons by crossing TGF-beta receptor I (TGF-beta RI) floxed mice with nestin-Cre mice. Almost all of the newborn cKO mice had retinal detachment at the retinal pigment epithelium (RPE)/photoreceptor layer junction of the neurosensory retina (NSR). The immunostaining for chondroitin-6-sulfate showed a very weak reaction in cKO mice in contrast to intense staining in the photoreceptor layer in wild-t ...[more]

PMID: 17126294

Similar Datasets

Project description:BackgroundInterleukin-33 (IL-33) belongs to the IL-1 cytokine family and resides in the nuclei of various cell types. In the neural retina, IL-33 is predominately expressed in Müller cells although its role in health and disease is ill-defined. Müller cell gliosis is a critical response during the acute phase of retinal detachment (RD), and in this study, we investigated if IL-33 was modulatory in the inflammatory and neurodegenerative pathology which is characteristic of this important clinical condition.MethodsRD was induced by subretinal injection of sodium hyaluronate into C57BL/6?J (WT) and IL-33-/- mice and confirmed by fundus imaging and optical coherence tomography (OCT). The expression of inflammatory cytokines, complement components and growth factors was examined by RT-PCR. Retinal neurodegeneration, Müller cell activation and immune cell infiltration were assessed using immunohistochemistry. The expression of inflammatory cytokines in primary Müller cells and bone marrow-derived macrophages (BM-DMs) was assessed by RT-PCR and Cytometric Bead Array.ResultsRD persisted for at least 28?days after the injection of sodium hyaluronate, accompanied by significant cone photoreceptor degeneration. The mRNA levels of CCL2, C1ra, C1s, IL-18, IL-1?, TNF?, IL-33 and glial fibrillary acidic protein (GFAP) were significantly increased at day 1 post-RD, reduced gradually and, with the exception of GFAP and C1ra, returned to the basal levels by day 28 in WT mice. In IL-33-/- mice, RD induced an exacerbated inflammatory response with significantly higher levels of CCL2, IL-1? and GFAP when compared to WT. Sustained GFAP activation and immune cell infiltration was detected at day 28 post-RD in IL-33-/- mice. Electroretinography revealed a lower A-wave amplitude at day 28 post-RD in IL-33-/- mice compared to that in WT RD mice. IL-33-/- mice subjected to RD also had significantly more severe cone photoreceptor degeneration compared to WT counterparts. Surprisingly, Müller cells from IL-33-/- mice expressed significantly lower levels of CCL2 and IL-6 compared with those from WT mice, particularly under hypoxic conditions, whereas IL-33-/- bone marrow-derived macrophages expressed higher levels of inducible nitric oxide synthase, TNF?, IL-1? and CCL2 after LPS?+?IFN? stimulation compared to WT macrophages.ConclusionIL-33 deficiency enhanced retinal degeneration and gliosis following RD which was related to sustained subretinal inflammation from infiltrating macrophages. IL-33 may provide a previously unrecognised protective response by negatively regulating macrophage activation following retinal detachment.

Project description:IntroductionRetinal detachment is a sight-threatening emergency, with more than half of those affected suffering permanent visual impairment. A diagnostic test to identify eyes at risk before vision is threatened would enable exploration of prophylactic treatment. This report presents the use of irregularities in retinal shape, quantified from optical coherence tomography (OCT) images, as a biomarker for retinal detachment.MethodsOCT images were taken from posterior and mid-peripheral retina of 264 individuals [97 after a posterior vitreous detachment (PVD), 99 after vitrectomy for retinal detachment and 68 after laser for a retinal tear]. Diagnoses were taken from history, examination and OCT. Retinal irregularity was quantified in the frequency domain, and the distribution of irregularity across the regions of the eye was explored to identify features exhibiting the greatest difference between retinal detachment and PVD eyes. Two of these features plus axial length were used to train a quadratic discriminant analysis classifier. Classifier performance was assessed by its sensitivity and specificity in identifying retinal detachment eyes and visualised with a receiver operating characteristic (ROC) curve.ResultsValidation set specificity was 84% (44/52 PVD eyes correctly labelled) and sensitivity 35% (23/64 retinal detachment eyes identified, p = 0.02). Area under the ROC curve was 0.75 (95% confidence intervals 0.58-0.85). Retinal detachment eyes were significantly more irregular than PVD eyes in the superior retina (0.70 mm versus 0.49 mm, p < 0.05) and supero-temporal retina (1.12 mm versus 0.80 mm, p < 0.05). Lower sensitivity (16/68, 24%) was seen for eyes with a retinal tear without detachment, that were intermediate in size between retinal detachment and PVD eyes. Axial length on its own was a poor classifier. Neither irregularity nor classification were affected by surgery for retinal detachment or the development of PVD.ConclusionsThe classifier identified 1/3 of retinal detachment eyes in this sample. In future work, these features can be evaluated as a test for retinal detachment prior to PVD.

Dataset Information

Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice.

Publications

Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets