RESUMEN
Glaucoma is characterized by retinal ganglion cell (RGC) degeneration and is the second leading cause of blindness worldwide. However, current treatments such as eye drop or surgery have limitations and do not target the loss of RGC. Regenerative therapy using embryonic stem cells (ESCs) holds a promising option, but ethical concern hinders clinical applications on human subjects. In this study, we employed spermatogonial stem cells (SSCs) as an alternative source of ESCs for cell-based regenerative therapy in mouse glaucoma model. We generated functional RGCs from SSCs with a two-step protocol without applying viral transfection or chemical induction. SSCs were first dedifferentiated to embryonic stem-like cells (SSC-ESCs) that resemble ESCs in morphology, gene expression signatures, and stem cell properties. The SSC-ESCs then differentiated toward retinal lineages. We showed SSC-ESC-derived retinal cells expressed RGC-specific marker Brn3b and functioned as bona fide RGCs. To allow in vivo RGC tracing, Brn3b-EGFP reporter SSC-ESCs were generated and the derived RGCs were subsequently transplanted into the retina of glaucoma mouse models by intravitreal injection. We demonstrated that the transplanted RGCs could survive in host retina for at least 10 days after transplantation. SSC-ESC-derived RGCs can thus potentially be a novel alternative to replace the damaged RGCs in glaucomatous retina.
Asunto(s)
Células Madre Germinales Adultas/citología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Glaucoma/terapia , Células Ganglionares de la Retina/trasplante , Células Madre Germinales Adultas/metabolismo , Animales , Biomarcadores/metabolismo , Diferenciación Celular , Modelos Animales de Enfermedad , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Expresión Génica , Genes Reporteros , Glaucoma/inducido químicamente , Glaucoma/genética , Glaucoma/patología , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Inyecciones Intravítreas , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , N-Metilaspartato/administración & dosificación , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Cultivo Primario de Células , Retina/efectos de los fármacos , Retina/metabolismo , Retina/patología , Células Ganglionares de la Retina/citología , Células Ganglionares de la Retina/metabolismo , Testículo/citología , Testículo/metabolismo , Factor de Transcripción Brn-3B/genética , Factor de Transcripción Brn-3B/metabolismoRESUMEN
UNLABELLED: We examined the prevalence of medical problems in children and teenagers with Down syndrome in Hong Kong. METHODS: Children with Down syndrome receiving care from seven regional hospitals were included and their hospital records were reviewed. A total of 407 patients, aged between 0.06 and 17.16 years were included. Cardiovascular problems were observed in 216 (53%), endocrine problems in 111 (27%), gastrointestinal problems in 46 (11%), haematological problems in 18 (4%), neurological problems in 27 (7%), sleep problems in 36 (9%), skeletal problems in 56 (14%), visual problems in 195 (48%) and auditory problems in 137 (34%). CONCLUSIONS: The prevalence of medical problems was high in children and teenagers with Down syndrome in Hong Kong and similar to previous findings elsewhere. Future studies on the local prevalence of medical problems in the adult population with Down syndrome would help to define their medical needs.
