2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38813An increasing trend of vision degenerative diseases has been found among Taiwan populations, with retinopathy being irreversible and liable to be a major cause of blindness. Homocysteine, an amino acid, is a precursor for biosynthesis of methionine. Folic acid deficiency may lead to accumulation of homocysteine and is closely relevant to vision degenerative diseases. Homocysteine accumulation in the human retina is mainly within Müller stem cells that are capable of self-renewal. As homocysteine is accumulated to a certain extent that impairs the self-renewal function of Müller stem cells, retinal degeneration and atrophy may be accelerated. We have established a mouse model on the vision degenerative diseases induced by hyperhomocysteine. Extensive retinal cell degeneration and increased number of Müller stem cells was found under hyperhomocysteine conditions. However, no apparent retinal repair was detected. Therefore, whether homocysteine can inhibit or interfere with the proliferation, differentiation, and migration of Müller stem cells remains to be elucidated. This project aims to extend our previous results by studying the stem cell characteristics of Müller cells and the dynamic changes of retinal cell populations under the influence of hyperhomocysteine. In addition, the hyperhomocysteine interference on the activation Müller stem cells will be reduced to determine whether visual function can be repaired. Furthermore, transplantation of Müller stem cells will be performed to mimic clinical therapy of retinopathy induced by hyperhomocysteine. We envisage that the data derived from this project will provide essential information regarding hyperhomocysteine-induced retinal degenerative diseases and provide new insights of treatment options. Moreover, new treatment strategy through Müller stem cell transplantation may be developed.視覺退化性疾病在台灣族群的發生率有逐年增高的趨勢，而視網膜的損失難以恢復且容易造成失明。「同半胱胺酸」是一種胺基酸，它是製造甲硫胺酸過程所需要的前驅物；葉酸的缺乏容易造成同半胱胺酸的堆積，同時與視覺退化有密切的關係。在人類視網膜組織，同半胱胺酸主要聚集於擁有再生分化的能力Müller stem cells，一旦這群幹細胞的功能受限，便加快視網膜組織的委縮退化。我們以提高眼球「同半胱胺酸」的表現建立了小鼠視覺退化模式，發現Müller stem cells數目增加，但是死亡的視網膜組織並無明顯的修補。然而，對於同半胱胺酸是否會造成限制或干擾Müller stem cells的增生、分化和移動，目前尚無定論。本計畫將延續初步的研究成果，深入分析在「同半胱胺酸」的作用之下，觀察Müller stem cells是否仍完整保有幹細胞的能力，並分析再生分化過程中之Müller幹細胞族群的變化。另外，在小鼠身上，我們嘗試地降低「同半胱胺酸」的干擾，同時促進Müller stem cells活化後，分析受損的視網膜如果被修復的同時是否也伴隨著視覺生理功能的恢復。最後，進行體外移植Müller stem cells到受損視網膜，模擬臨床上的治療，尋求視覺修復的最佳方法。預期本計畫的實驗成果將提供「同半胱胺酸」在「視網膜退化」的理論證據，因而改變臨床治療與視力保健的基本概念，可能因此開發出新的幹細胞治療策略。米勒細胞視網膜幹細胞視網膜退化同半胱胺酸實驗性幹細胞治療Muller stem cellretinal stem cellretinal degenerationhomocysteineexperimental stem cell therapyProject