Preclinical validation of the regenerative potential of retinal ganglion cells (RGC) derived from Muller stem cells

源自 Muller 干细胞的视网膜神经节细胞 (RGC) 再生潜力的临床前验证

• 批准号: G0900002/1
• 负责人: Gloria Limb
• 金额: $ 91.02万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900002%2F1
• 关键词: Preclinical; validation; regenerative; potential; retinal

The research is aimed at developing preclinical studies for the design of cell based therapies to treat advanced glaucoma. Glaucoma is an eye disease characterized by damage to specialized neurons of the retina (known as ganglion cells) and the optic nerve (the part that connects the eye to the brain). This disease constitutes a common cause of severe vision impairment and blindness. This investigation stems from our previous demonstration that a population of adult human retinal stem cells discovered in our laboratory and known as Muller stem cells, have the ability to differentiate into ganglion cells and to restore the visual response to very dim light in animals depleted of ganglion cells. To advance our work towards the development of human therapies, we aim to validate our previous findings using an experimental eye model that is close to humans. We will therefore investigate whether transplantation of Muller stem cells differentiated into ganglion cells are able to restore visual function in the feline retina after chemical depletion of these cells. We have isolated and characterized Muller stem cells from the cat retina and can propagate these cells for transplantation. The main objectives of our proposed research are i) to isolate and propagate Muller stem cells from the cat retina and to differentiate these cells into ganglion cells for transplantation, ii) to induce ganglion cell depletion in the cat retina by intraocular injection of neurotoxins, and to repopulate these cells with differentiated ganglion cells iii) to assess retinal function in the transplanted animals by examination of their visual function in response to light, and iv) to examine the localization of transplanted cells into the retina, as well as to assess the long term survival of these cells. On this basis, our ultimate aim is to advance this research into an immediate translational stage towards the development of human therapies.

这项研究的目的是开发临床前研究，以设计基于细胞的疗法来治疗晚期青光眼。青光眼是一种眼病，其特征是视网膜(称为神经节细胞)和视神经(连接眼睛和大脑的部分)的专门神经元受损。这种疾病是导致严重视力障碍和失明的常见原因。这项研究源于我们之前的演示，即在我们实验室发现的一群被称为Muller干细胞的成人人类视网膜干细胞，具有分化为神经节细胞的能力，并在耗尽神经节细胞的动物中恢复对非常暗淡的光的视觉反应。为了推动人类疗法的发展，我们的目标是使用接近人类的实验性眼睛模型来验证我们之前的发现。因此，我们将研究移植分化为神经节细胞的Muller干细胞是否能够在这些细胞化学耗尽后恢复猫视网膜的视觉功能。我们已经从猫的视网膜中分离并鉴定了Muller干细胞，并可以繁殖这些细胞进行移植。我们提出的研究的主要目标是：i)分离和繁殖猫视网膜的Muller干细胞，并将这些细胞分化为神经节细胞进行移植；ii)通过眼内注射神经毒素诱导猫视网膜中的神经节细胞枯竭，并将分化的神经节细胞重新植入这些细胞；iii)通过检查移植动物的视觉功能对光的反应来评估移植动物的视网膜功能；以及iv)检测移植细胞在视网膜中的定位以及评估这些细胞的长期存活。在此基础上，我们的最终目标是将这项研究推进到人类疗法发展的直接翻译阶段。