Publications by authors named "L Alan Todd"

Retinal degeneration in mammals causes permanent loss of vision, due to an inability to regenerate naturally. Some non-mammalian vertebrates show robust regeneration, via Muller glia (MG). We have recently made significant progress in stimulating adult mouse MG to regenerate functional neurons by transgenic expression of the proneural transcription factor Ascl1.

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The spleen is an important immune organ in adult Xenopus laevis, supporting the differentiation of B cells and acting as the main peripheral lymphoid organ. Key to these processes are the supporting non-hematopoietic cells, or stromal cells, within the spleen tissue. Despite the importance of the spleen to frog immunity, few frog cell lines originating from spleen tissue have been reported.

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We summarize recent findings in different animal models regarding the different cell-signaling pathways and gene networks that influence the reprogramming of Müller glia into proliferating, neurogenic progenitor cells in the retina. Not surprisingly, most of the cell-signaling pathways that guide the proliferation and differentiation of embryonic retinal progenitors also influence the ability of Müller glia to become proliferating Müller glia-derived progenitor cells (MGPCs). Further, the neuronal differentiation of MGPC progeny is potently inhibited by networks of neurogenesis-suppressing genes in chick and mouse models but occurs freely in zebrafish.

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This video article presents a case study of a 70-year-old male with medically refractory essential tremor treated with magnetic resonance-guided focused ultrasound (MRgFUS). Following an initial successful ablation of the right thalamus, the patient underwent left-sided thalamotomy. After two tractography-guided sonications, the authors observed a significant reduction in his right-hand tremor with no immediate side effects.

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Article Synopsis
  • Endogenous reprogramming of glial cells, specifically Müller glia, shows potential for neuron restoration in the adult retina by using strategies adapted from regenerative species.
  • The transcription factor Ascl1 can induce some Müller glia to regenerate neurons, but this process is hindered by neuroinflammation from infiltrating monocytes from the peripheral immune system.
  • Preventing monocyte infiltration enhances the neurogenic capacity of Müller glia, suggesting that targeting peripheral immune responses could improve neuronal regeneration therapies in the central nervous system.
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