Inflamed In Vitro Retina: Cytotoxic Neuroinflammation and Galectin-3 Expression

Autor: Ulrica Englund-Johansson, Hodan Abdshill, Tomas Deierborg, Patrik Bauer, Fredrik Johansson, Marina Castro Zalis
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Lipopolysaccharides
Macroglial Cells
Lipopolysaccharide
Physiology
medicine.medical_treatment
Galectin 3
lcsh:Medicine
Apoptosis
chemistry.chemical_compound
Mice
0302 clinical medicine
Animal Cells
Immune Physiology
Medicine and Health Sciences
lcsh:Science
Immune Response
Neurons
Innate Immune System
Multidisciplinary
Microglia
Cell Death
Microfilament Proteins
Ectodysplasins
Cell biology
medicine.anatomical_structure
Cytokine
Cell Processes
Cytokines
Anatomy
Cellular Types
Neuronal Tuning
medicine.drug
Research Article
Interleukin 2
Ocular Anatomy
Immunology
Glial Cells
Biology
In Vitro Techniques
Retina
03 medical and health sciences
Immune system
Ocular System
Glial Fibrillary Acidic Protein
medicine
Animals
Microglial Cells
Neuroinflammation
Inflammation
Interleukin-6
Tumor Necrosis Factor-alpha
lcsh:R
Calcium-Binding Proteins
Biology and Life Sciences
Retinal
Cell Biology
Molecular Development
030104 developmental biology
Ki-67 Antigen
chemistry
Gene Expression Regulation
Immune System
Astrocytes
Interleukin-2
lcsh:Q
030217 neurology & neurosurgery
Developmental Biology
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 9, p e0161723 (2016)
ISSN: 1932-6203
Popis: BACKGROUND:Disease progression in retinal neurodegeneration is strongly correlated to immune cell activation, which may have either a neuroprotective or neurotoxic effect. Increased knowledge about the immune response profile and retinal neurodegeneration may lead to candidate targets for treatments. Therefore, we have used the explanted retina as a model to explore the immune response and expression of the immune modulator galectin-3 (Gal-3), induced by the cultivation per se and after additional immune stimulation with lipopolysaccharide (LPS), and how this correlates with retinal neurotoxicity. METHODS:Post-natal mouse retinas were cultured in a defined medium. One group was stimulated with LPS (100 ng/ml, 24 h). Retinal architecture, apoptotic cell death, and micro- and macroglial activity were studied at the time of cultivation (0 days in vitro (DIV)) and at 3, 4 and 7 DIV using morphological staining, biochemical- and immunohistochemical techniques. RESULTS:Our results show that sustained activation of macro- and microglia, characterized by no detectable cytokine release and limited expression of Gal-3, is not further inducing apoptosis additional to the axotomy-induced apoptosis in innermost nuclear layer. An elevated immune response was detected after LPS stimulation, as demonstrated primarily by release of immune mediators (i.e. interleukin 2 (IL-2), IL-6, KC/GRO (also known as CLCX1) and tumour necrosis factor-α (TNF-α)), increased numbers of microglia displaying morphologies of late activation stages as well as Gal-3 expression. This was accompanied with increased apoptosis in the two additional nuclear layers, and damage to retinal gross architecture. CONCLUSION:We demonstrate that an immune response characterized by sustained and increased release of cytokines, along with an increase in Gal-3 expression, is accompanied by significant increased neurotoxicity in the explanted retina. Further investigations using the current setting may lead to increased understanding on the mechanisms involved in neuronal loss in retinal neurodegenerations.
Databáze: OpenAIRE
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