NeuroD誘導視網膜色素上皮細胞轉分化為類視網膜細胞

Retinal Transdifferentiation Induced by NeuroD on Retinal Pigmented Epithelial Cells

感光細胞為脊椎動物眼睛主要的感覺感受器。而感光細胞是一種具有光色素的特化神經細胞，這些已分化完全的特化細胞一旦受到過量的刺激而細胞遭受破壞，即無法進行細胞修復或再生，造成不可逆的視覺退化疾病。此感光細胞的視網膜退化疾病常是臨床上病人失去視力的主要原因。目前對於視網膜退化疾病的治療方式，均無有效且可逆的治療方法，因此今年來的幹細胞或新培育視網膜細胞植入治療便成為一種具有潛力治癒視網膜退化疾病的方法。本研究是利用視網膜色素上皮細胞（RPE cell）可再生和培育的特性，誘導視網膜特化基因NeuroD 進入細胞中，以誘導視網膜色素上皮細胞轉分化為視網膜的細胞，使視網膜色素上皮細胞作為幹細胞來源，且分化為特定視網膜疾病需要的視網膜細胞或視網膜前趨細胞，以提供移植治療之用。本研究發現，NeuroD 基因轉殖到視網膜色素上皮細胞後，可誘導細胞表現特定的視網膜細胞標的物質，顯示可能分化為感光細胞、神經節細胞、兩極細胞、水平細胞、無長突細胞等各種視網膜細胞。此結果顯示NeuroD誘導的視網膜色素上皮細胞可能為治療視網膜退化疾病之可用細胞材料。

The receptors for light in the vertebrate eye are photoreceptors of the retina. Photoreceptors are a group of light-sensitive receptor neurons which are terminal differentiated that do not divide and are not replaced if destroyed. The degenerative diseases of photoreceptors is a common cause of losing sight in retina. One of the treatment for retinal regeneration is to re-supply the type of cells that were damaged with neural progenitor cells or stem cells. The retinal pigmented epithelium (RPE) is the pigmented cell layer lies adjacent to photoreceptors that can reenter the cell cycle under certain trigger. This makes RPE as one of the stem cell sources to differentiate into neural progenitor cells or retinal precursor cells. In chick retina, the determination of the photoreceptor cell’s fate may involve NeuroD, which is homologous to the drosophila proneural gene atonal. In addition, an overproduction of photoreceptor cells in the developing chick retina under retrovirus-driven NeuroD expression. In this study, The NeuroD gene was transfected into the RPE cells and some of the cells showed immunoreactivity for rhodopsin. The results demonstrate that RPE cells can be directed to photoreceptor fate and thus may be useful in the treatment of retinal degenerative diseases.