Clinical trial of cone photoreceptor transplantation for the treatment of retinal degeneration

人眼利用两种类型的感光细胞：视杆细胞和视锥细胞。其中，视锥细胞在白天活跃，负责提供详细（阅读）视觉，迄今为止对日常生活最为重要。在视锥细胞营养不良或Stargardt病等情况下，视锥细胞会随着时间的推移而死亡，由于人体无法替换这些细胞，这导致了严重的视力障碍。在这个项目中，我们的目标是创造一种可移植的视锥细胞来源，并测试将这些细胞移植到人眼中是否能恢复晚期视锥细胞营养不良患者失去的视力。在之前的一个项目中，我们已经证明，我们可以在实验室中培养人类视锥细胞，使用适合随后移植到患者体内的方法。当我们将这些细胞移植到缺乏所有光敏细胞的老鼠身上时，我们可以证明人类细胞存活了下来，并与老鼠的神经细胞建立了联系。结果，老鼠的眼睛恢复了对光的感觉，动物的行为也随着对光的反应而改变，这表明一些视力得到了恢复。该项目的目的是：(1)扩大视锥细胞的生产方法，使其能够制造足够的细胞用于治疗人眼；(2)生产大量符合人类使用质量规定的视锥细胞；(3)将这些视锥细胞移植到多达12名晚期视锥细胞营养不良患者的眼睛中。由于这是我们第一次测试这些细胞，患者研究的主要目的将是确定视锥细胞移植是否安全。第二个目的是通过一系列视力测试来确定移植的视锥细胞是否能够存活并恢复视力。如果研究成功，我们将进一步发展移植方法，以能够治疗越来越多的致盲疾病。

The human eye makes use of two types of light-sensing cells, rods and cones. Of the two, the cones, which are active in daylight and which confer detailed (reading) vision, are by far the most important for day-to-day life. In conditions like cone dystrophy or Stargardt disease, the cone cells die over time, and as the human body is unable to replace these cells, this results in severe vision impairment. In this project we aim to create a source of transplantable cone cells and test whether the transplantation of these cells into the human eye can restore the vision that is lost in patients with advanced cone dystrophy. In a previous project, we have shown that we can grow up human cones in the laboratory using methods that make them suitable for subsequent transplantation into patients. When we transplanted these cells into mice that lack all light-sensing cells, we could prove that the human cells survived and made connections with the nerve cells of the mouse. As a result, light-sensation was restored in the mouse eye and the animal's behaviour changed in response to light, indication that some vision was restored. The aim of this project is to (1) scale-up the cone production method to be able to make enough cells for treating the human eye, (2) produce a large batch of cones that passes the quality regulations for human use, and (3) transplant these cone cells into the eyes of up to 12 patients with advanced cone dystrophy. As this is the first time that we test these cells the primary objective of the patient study will be to establish whether the transplantation of cones is safe. The secondary objective is to determine whether the transplanted cone cells can survive and restore vision, using a range of vision tests. If the study is successful, we will develop the transplantation method further to be able to treat a increasing range of blinding diseases.