15 research outputs found
Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium
Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies
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Genetic interactions of cell intrinsic factors and secreted signals regulate neurogenesis in olfactory epithelium / 細胞内因子と分泌シグナル因子の反作用による嗅覚上皮神経発生の制御
我 々 は こ れ まで に、TGF 一βフ ァ ミ リーの 分泌 因子 で あ る Gdf11 や Activinβ B が 嗅覚上 皮 の 発 生 を負 に
制御す る こ とを見出 した 。 さ らに 、転 写因了一Foxg1 が TGF 一βフ ァ ミ リーの 分 泌 因 子 Gdfl1 の 活性制御 を通
じて 嗅覚上 皮 の 発 生 に 関与 す る こ と を、マ ウ ス の 遺伝学的 手 法 を用 い て 発 見 し た。こ れ らの 結 果 は 、Foxg1
と フ ォ リス タ チ ン (Fst)を介 した、Gdfl・1 の 「負の フ ィ ー ドバ ッ ク機構」の 適 切な制御が 、嗅覚上 皮 の 層構
造 形 成 (histogcnesis)お よ び 鼻甲介形成 (morphogcnesis )の 両 方 に 重 要 で あ る が 、そ の 制 御 機構 に は 差 異が
あ る こ とを示 して い る 。 / It has so far, it was found that TGF-β family of secreted factors and is Gdf11 and ActivinβB to control the negative occurrence of the olfactory epithelium. In addition, the transcription factor Foxg1 is to be involved in the development of the olfactory epithelium through active control of secreted factors Gdf11 of the TGF-β family, was discovered using genetic techniques in mice. These results, through the Foxg1 and follistatin (Fst), appropriate control of the "negative feedback mechanism" of Gdf11 is, important to both of the layer structure formation of the olfactory epithelium (histogenesis) and nasal turbinates formation (morphogenesis) although, it is shown that there are differences in the control mechanism
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Genetic interactions of cell intrinsic factors and secreted signals regulate neurogenesis in olfactory epithelium / 細胞内因子と分泌シグナル因子の反作用による嗅覚上皮神経発生の制御
我 々 は こ れ まで に、TGF 一βフ ァ ミ リーの 分泌 因子 で あ る Gdf11 や Activinβ B が 嗅覚上 皮 の 発 生 を負 に
制御す る こ とを見出 した 。 さ らに 、転 写因了一Foxg1 が TGF 一βフ ァ ミ リーの 分 泌 因 子 Gdfl1 の 活性制御 を通
じて 嗅覚上 皮 の 発 生 に 関与 す る こ と を、マ ウ ス の 遺伝学的 手 法 を用 い て 発 見 し た。こ れ らの 結 果 は 、Foxg1
と フ ォ リス タ チ ン (Fst)を介 した、Gdfl・1 の 「負の フ ィ ー ドバ ッ ク機構」の 適 切な制御が 、嗅覚上 皮 の 層構
造 形 成 (histogcnesis)お よ び 鼻甲介形成 (morphogcnesis )の 両 方 に 重 要 で あ る が 、そ の 制 御 機構 に は 差 異が
あ る こ とを示 して い る 。 / It has so far, it was found that TGF-β family of secreted factors and is Gdf11 and ActivinβB to control the negative occurrence of the olfactory epithelium. In addition, the transcription factor Foxg1 is to be involved in the development of the olfactory epithelium through active control of secreted factors Gdf11 of the TGF-β family, was discovered using genetic techniques in mice. These results, through the Foxg1 and follistatin (Fst), appropriate control of the "negative feedback mechanism" of Gdf11 is, important to both of the layer structure formation of the olfactory epithelium (histogenesis) and nasal turbinates formation (morphogenesis) although, it is shown that there are differences in the control mechanism
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Negative Regulation of Endogenous Stem Cells in Sensory Neuroepithelia: Implications for Neurotherapeutics
Stem cell therapies to treat central nervous system (CNS) injuries and diseases face many obstacles, one of which is the fact that the adult CNS often presents an environment hostile to the development and differentiation of neural stem and progenitor cells. Close examination of two regions of the nervous system – the olfactory epithelium (OE), which regenerates, and the neural retina, which does not – have helped identify endogenous signals, made by differentiated neurons, which act to inhibit neurogenesis by stem/progenitor cells within these tissues. In this chapter, we provide background information on these systems and their neurogenic signaling systems, with the goal of providing insight into how manipulation of endogenous signaling molecules may enhance the efficacy of stem cell neurotherapeutics