cyclin-d1 and Retinal-Diseases

Topics: Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Choroid Diseases; Cyclin D1; Cyclophosphamide; Doxorubicin; Flow Cytometry; Humans; Lymphoma, Mantle-Cell; Male; Middle Aged; Orbital Neoplasms; Pleural Effusion; Positron-Emission Tomography; Prednisone; Retinal Diseases; Rituximab; Tomography, X-Ray Computed; Vincristine; Vision Disorders; Visual Acuity

Müller glia, the principal glial cell type in the retina, have the potential to proliferate and regenerate neurons after retinal damage. However, unlike the situation in fish and birds, this capacity of Müller glia is extremely limited in mammals. To gain new insights into the mechanisms that hamper retinal regeneration in mammals, we examined the cell cycle progression and DNA damage response in Müller glia after retinal damage.. Expression of cell cycle-related proteins and DNA damage response were analyzed in adult rat and mouse retinas after N-methyl-N-nitrosourea (MNU)- or N-methyl-D-aspartate (NMDA)-induced retinal damage. Zebrafish and postnatal rat retinas were also investigated for comparison. Analysis was conducted by using immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction.. In the rat retina, most Müller glia reentered the cell cycle after MNU-induced photoreceptor damage while no proliferative response was observed in the mouse model. Cell cycle reentry of rat Müller glia was accompanied by DNA damage response including the phosphorylation of the histone variant H2AX and upregulation of p53 and p21. The DNA damage response was also observed in rat Müller glia after NMDA-induced loss of inner retinal neurons, but not in zebrafish Müller glia or rat retinal progenitor cells.. Our findings suggest that the DNA damage response induced by unscheduled cell cycle reentry may be one of the mechanisms that limit the proliferative and regenerative capacity of Müller glia in the mammalian retina.

Topics: Animals; Blotting, Western; Cell Count; Cell Cycle; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase 4; Disease Models, Animal; DNA Damage; Ependymoglial Cells; Gene Expression Regulation; Immunohistochemistry; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred C57BL; Nerve Regeneration; Photoreceptor Cells; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Retina; Retinal Diseases; Retinal Neurons; RNA

To investigate whether lipid peroxides play a role in retinal cell death due to ischemia-reperfusion injury, whether recombinant human thioredoxin (rhTRX) treatment reduces production of lipid peroxides of the retina, and whether such treatment reduces the number of cells expressing c-Jun and cyclin D1.. Retinal ischemia was induced in rats by increasing the intraocular pressure to 110 mm Hg for 60 minutes. After reperfusion, immunohistochemical staining for lipid peroxide, peroxynitrite, c-Jun, and cyclin D1 and propidium iodide (PI) staining were performed on retinal sections from animals treated intravenously with and without rhTRX, a free radical scavenger. Quantitative analyses of PI-, c-Jun-, and cyclin D1-positive cells were performed after the ischemic insult. Concentration of lipid peroxides in the retina was determined by the thiobarbituric acid assay.. Specific immunostaining for lipid peroxides was seen in the ganglion cell layer at 6 hours after reperfusion, in the inner nuclear layer at 12 hours, and in the outer nuclear layer at 48 hours. Time course studies for PI-positive cells in the three nuclear layers coincided with those of specific immunostaining for lipid peroxides. The specific immunostaining was weakened by pre- and posttreatment with 0.5 mg of rhTRX. The number of PI-, c-Jun-, and cyclin D1-positive cells and the concentration of lipid peroxides were significantly decreased by treatment with rhTRX compared with those of vehicle-treated control rats (P: < 0. 01).. Lipid peroxides formed by free radicals may play a role in neuronal cell death in retinal ischemia-reperfusion injury.

Topics: Aldehydes; Animals; Cell Death; Cyclin D1; Fluorescent Antibody Technique, Indirect; Free Radical Scavengers; Lipid Peroxidation; Lipid Peroxides; Male; Nitrates; Propidium; Proto-Oncogene Proteins c-jun; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Reperfusion Injury; Retina; Retinal Diseases; Thiobarbituric Acid Reactive Substances; Thioredoxins