RESUMO
Müller glia can serve as a source of new neurons after retinal damage in both fish and birds. Investigations of regeneration in the mammalian retina in vitro have provided some evidence that Müller glia can proliferate after retinal damage and generate new rods; however, the evidence that this occurs in vivo is not conclusive. We have investigated whether Müller glia have the potential to generate neurons in the mouse retina in vivo by eliminating ganglion and amacrine cells with intraocular NMDA injections and stimulating Müller glial to re-enter the mitotic cycle by treatment with specific growth factors. The proliferating Müller glia dedifferentiate and a subset of these cells differentiated into amacrine cells, as defined by the expression of amacrine cell-specific markers Calretinin, NeuN, Prox1, and GAD67-GFP. These results show for the first time that the mammalian retina has the potential to regenerate inner retinal neurons in vivo.
Assuntos
Regeneração Nervosa/fisiologia , Neuroglia/citologia , Neurônios/citologia , Retina/citologia , Retina/fisiologia , Células Amácrinas/citologia , Células Amácrinas/metabolismo , Animais , Biomarcadores/metabolismo , Calbindina 2 , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Linhagem da Célula/fisiologia , Proteínas de Ligação a DNA , Denervação , Agonistas de Aminoácidos Excitatórios/toxicidade , Glutamato Descarboxilase/metabolismo , Proteínas de Fluorescência Verde , Proteínas de Homeodomínio/metabolismo , Camundongos , Camundongos Transgênicos , N-Metilaspartato/toxicidade , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Proteínas Nucleares/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
The cationic complexes (1,2-diaminoethane)(maltolato)platinum(II) ([Pt(en)(ma)]+) and (1R,2R-1,2-diaminocyclohexane)(maltolato)platinum(II) ([Pt(R,R-DACH)(ma)]+) have been prepared and the structure of [Pt(R,R-DACH)(ma)]NO3 has been determined by single crystal X-ray diffraction. The geometry of the metal in [Pt(R,R-DACH)(ma)]NO3 is essentially square planar and the maltolate ligand has a geometry similar to other chelate complexes involving this ligand. The cytotoxicities of the compounds have been assessed in the human cell lines HeLa and K562 and the IC50 values are approximately 32 microM in HeLa cells and 26 microM in K562 cells. In these cell lines the cytotoxicity of cisplatin is higher than the maltolate complexes by a factor of 2 to 3 whereas the cytotoxicity of carboplatin is lower than the maltolate complexes.