Loss of the Extracellular Matrix Molecule Tenascin-C Leads to Absence of Reactive Gliosis and Promotes Anti-inflammatory Cytokine Expression in an Autoimmune Glaucoma Mouse Model

Previous studies demonstrated that retinal damage correlates with a massive remodeling of extracellular matrix (ECM) molecules and reactive gliosis. However, the functional significance of the ECM in retinal neurodegeneration is still unknown. In the present study, we used an intraocular pressure (IOP) independent experimental autoimmune glaucoma (EAG) mouse model to examine the role of the ECM glycoprotein tenascin-C (Tnc). Wild type (WT ONA) and Tnc knockout (KO ONA) mice were immunized with an optic nerve antigen (ONA) homogenate and control groups (CO) obtained sodium chloride (WT CO, KO CO). IOP was measured weekly and electroretinographies were recorded at the end of the study. Ten weeks after immunization, we analyzed retinal ganglion cells (RGCs), glial cells, and the expression of different cytokines in retina and optic nerve tissue in all four groups. IOP and retinal function were comparable in all groups. Although RGC loss was less severe in KO ONA, WT as well as KO mice displayed a significant cell loss after immunization. Compared to KO ONA, less βIII-tubulin+ axons, and downregulated oligodendrocyte markers were noted in WT ONA optic nerves. In retina and optic nerve, we found an enhanced GFAP+ staining area of astrocytes in immunized WT. A significantly higher number of retinal Iba1+ microglia was found in WT ONA, while a lower number of Iba1+ cells was observed in KO ONA. Furthermore, an increased expression of the glial markers Gfap, Iba1, Nos2, and Cd68...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

Related Links:

Circular RNAs are characterized as a class of covalently closed circular RNA transcripts and are associated with a variety of cellular processes and neurological diseases by sponging microRNAs. Expression profiling of circular RNAs in glaucoma, which is a form of optic neuropathy, has not been performed to date. The most common characteristic of all forms of glaucoma is the loss of retinal ganglion cells. While the pathogenesis of glaucoma is not fully understood, intraocular pressure is unquestionably the only proven modifiable factor which makes chronic ocular hypertension (COH) animals the classical glaucoma models. Bas...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Authors: Kikuchi K, Dong Z, Shinmei Y, Murata M, Kanda A, Noda K, Harada T, Ishida S Abstract Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies. Lowering intraocular pressure is currently the only way to treat glaucoma, but it is often insufficient to inhibit the progression of the disease. Glaucoma is a multifactorial disease, and the involvement of oxidative stress has recently received much attention. In the present study, we investigated the cytoprotective effect of astaxanthin (AST) on RGC degeneration using a normal-tension glaucoma (NTG...
Source: Journal of Ophthalmology - Category: Opthalmology Tags: J Ophthalmol Source Type: research
Authors: Tsai JC Abstract While sustained reduction of intraocular pressure (IOP) has been shown to halt and/or delay the progressive death of retinal ganglion cells (RGCs) in glaucoma, there exists great interest in the development and validation of IOP-independent therapeutic strategies for neuroprotection and/or neuroregeneration. Multiple etiologies for RGC death have been implicated in glaucoma including defective axonal transport, ischemia, excitotoxicity, reactive oxygen species, trophic factor withdrawal, and loss of RGC electrical activity. However, IOP lowering with medical, laser, and surgical therapies ...
Source: Journal of Ophthalmology - Category: Opthalmology Tags: J Ophthalmol Source Type: research
This study was designed to investigate the role of PR-619 in regulating mitophagy of RGCs under glutamate excitotoxicity. Primary cultured RGCs were incubated with PR-619 or vehicle control in the excitotoxicity model of 100 µM glutamate treatment. Mitochondrial membrane potential was assessed by JC-1 assay. Cytotoxicity of RGCs was measured by LDH activity. Proteins levels of parkin, optineurin, LAMP1, Bax, Bcl-2 and the LC3-II/I ratio were analyzed by western blot. The distribution and morphology of mitochondria in RGCs was stained by MitoTracker and antibody against mitochondria membrane protein, and examined by c...
Source: NeuroReport - Category: Neurology Tags: Degeneration and Repair Source Type: research
CONCLUSION: Our results indicated that the neuroprotective effects of overexpressed S100A4 on RGCs by activating Akt pathway and then inhibiting the apoptosis of cells after I/R injury. S100A4 protein may be a novel therapeutic target for glaucoma. PMID: 33031790 [PubMed - as supplied by publisher]
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
CONCLUSIONS A single injection of hydrogel into the anterior chamber is effective for modeling COH, can respond to most commonly used hypotensive drugs, and is non-toxic to the eyes. PMID: 32997651 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
This article provides a comprehensive review of the effect of oxidative stress, diet, and antioxidant therapy on IOP and open-angle glaucoma. PMID: 33008269 [PubMed - as supplied by publisher]
Source: European Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Eur J Ophthalmol Source Type: research
Conclusions: Significant macular microvascular damage was present in glaucomatous eyes without detectable 10-2 visual field damage. The damage of inferior perifoveal vessel density was more significant in early glaucoma. Macular microvascular damage spatially corresponded with functional and structural damage.
Source: Journal of Glaucoma - Category: Opthalmology Tags: Original Studies Source Type: research
DiscussionTo the best of our knowledge, the GSHM study is the first RCT to investigate the impact of medically lowering IOP in GSHM. The results will have implications for the clinical management of GSHM.Trial registrationClinicalTrials.govNCT04296916. Registered on 4 March 2020
Source: Trials - Category: Research Source Type: clinical trials
To investigate whether progressive macular ganglion cell –inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thinning are predictive for detecting visual field (VF) progression in eyes with high myopia.
Source: American Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Original Articles Source Type: research
More News: Allergy & Immunology | Brain | Chloride | Ganglions | Glaucoma | Neurology | Sodium | Sodium Chloride | Study | Vitamin A