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      Effects of Chymase on the Macular Region in Monkeys and Porcine Müller Cells: Probable Involvement of Chymase in the Onset of Idiopathic Macular Holes

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          Objectives: To investigate chymase involvement in idiopathic macular hole onset, the effects of chymase on monkey eyes and cultured Müller cells were investigated. Methods: Immunohistochemistry using antinestin and antiglial fibrillary acidic protein antibodies was performed in a normal monkey eye. After chymase was injected into the monkey vitreous, histological changes in the retina were evaluated using the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Expression of c-kit, a stem cell factor receptor, and nestin was examined in porcine Müller cells cultured with basic fibroblast growth factor. The effects of chymase on proliferation and TUNEL staining in Müller cells were also examined. Results: The number of nestin and glial fibrillary acidic protein-positive cells was higher in the macula than in other regions. Thickening of the posterior hyaloid membrane and some apoptotic cells were found in the macula of chymase-treated eyes. The expression of c-kit and nestin in Müller cells was shown and enhanced when cultured with basic fibroblast growth factor. Exposure to chymase inhibited Müller cell proliferation and produced TUNEL-positive cells. Conclusions: There might be Müller cells possessing atypical properties near the macular region and chymase might cause fibrosis and apoptosis through these cells. These findings suggest that increased chymase activity may result in idiopathic macular hole onset.

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          Most cited references 17

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          CNS stem cells express a new class of intermediate filament protein.

          Multipotential CNS stem cells receive and implement instructions governing differentiation to diverse neuronal and glial fates. Exploration of the mechanisms generating the many cell types of the brain depends crucially on markers identifying the stem cell state. We describe a gene whose expression distinguishes the stem cells from the more differentiated cells in the neural tube. This gene was named nestin because it is specifically expressed in neuroepithelial stem cells. The predicted amino acid sequence of the nestin gene product shows that nestin defines a distinct sixth class of intermediate filament protein. These observations extend a model in which transitions in intermediate filament gene expression reflect major steps in the pathway of neural differentiation.
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            Retinal stem cells in the adult mammalian eye.

            The mature mammalian retina is thought to lack regenerative capacity. Here, we report the identification of a stem cell in the adult mouse eye, which represents a possible substrate for retinal regeneration. Single pigmented ciliary margin cells clonally proliferate in vitro to form sphere colonies of cells that can differentiate into retinal-specific cell types, including rod photoreceptors, bipolar neurons, and Müller glia. Adult retinal stem cells are localized to the pigmented ciliary margin and not to the central and peripheral retinal pigmented epithelium, indicating that these cells may be homologous to those found in the eye germinal zone of other nonmammalian vertebrates.
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              Müller glia are a potential source of neural regeneration in the postnatal chicken retina.

              The retina of warm-blooded vertebrates is believed to be incapable of neural regeneration. Here we provide evidence that the retina of postnatal chickens has the potential to generate new neurons. In response to acute damage, numerous Müller glia re-entered the cell cycle, and shortly thereafter, expressed CASH-1, Pax6 and Chx10, transcription factors expressed by embryonic retinal progenitors. These progenitor-like cells transiently expressed neurofilament. Newly formed cells became distributed throughout the inner and outer nuclear layers of the retina, and remained for at least three weeks after damage. Some of these newly formed cells differentiated into retinal neurons, a few formed Müller glia, and most remained undifferentiated, with continued expression of Pax6 and Chx10. These cells continued to proliferate when grown in culture, with some differentiating into retinal neurons or Müller glia. We propose that, in response to damage, Müller glia in the retina are a potential source of neural regeneration.

                Author and article information

                Ophthalmic Res
                Ophthalmic Research
                S. Karger AG
                August 2006
                10 August 2006
                : 38
                : 4
                : 201-208
                Departments of aOphthalmology and bPharmacology, Osaka Medical College, Takatsuki, Osaka, and cNakamura Eye Clinic, Matsumoto, Nagano, Japan
                93072 Ophthalmic Res 2006;38:201–208
                © 2006 S. Karger AG, Basel

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                Figures: 8, References: 28, Pages: 8
                Original Paper


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