日本用基因疗法治疗眼疾实验取得成功

近日，医学界为患有遗传性眼疾的患者带来了一个振奋人心的消息，日本大阪大学蛋白质研究所采用基因疗法，在治疗可导致失明的遗传性眼疾“视网膜色素变性症”的实验上取得成功。

“视网膜色素变性症”是由于感光视网膜细胞渐渐被破坏而导致视野变窄的一种眼疾。医学界认为这是导致失明的三大原因之一，其主要原因是与遗传基因Crx的变异有关，表现为从婴幼儿起就出现视力障碍，平均每3000－4000人中就有1人患上此病，并且没有有效的治疗方法。

大阪大学的研究团队对刚刚出生且缺乏Crx遗传基因的实验鼠进行了实验，将这种基因植入这些实验鼠中，15周后在电子显微镜下观察发现实验鼠长出了视觉细胞，并且可以测定出从视网膜发送到大脑的电子信号，证明视网膜的生理机能得到了恢复。
研究团队表示，要全面评价实验还需要展开更多的测试和研究，但这一成果为基因疗法应用于更多眼疾奠定了基础。

G9a Histone Methyltransferase Activity in Retinal Progenitors Is Essential for Proper Differentiation and Survival of Mouse Retinal Cells

Kimiko Katoh, Ryoji Yamazaki, Akishi Onishi, Rikako Sanuki, and Takahisa Furukawa

In vertebrate retinal development, various transcription factors are known to execute essential activities in gene regulation. Although epigenetic modification is considered to play a pivotal role in retinal development, the exact in vivo role of epigenetic regulation is still poorly understood. We observed that G9a histone methyltransferase, which methylates histone H3 at lysine 9 (H3K9), is substantially expressed in the mouse retina throughout development. To address in vivo G9a function in the mouse retina, we ablated G9a in retinal progenitor cells by conditional gene knock-out (G9a Dkk3 CKO). The G9a Dkk3 CKO retina exhibited severe morphological defects, including photoreceptor rosette formation, a partial loss of the outer nuclear layer, elevated cell death, and persistent cell proliferation. Progenitor cell-related genes, including several cyclins, Hes1, Chx10, and Lhx2, are methylated on histone H3K9 in the wild-type retina, but they were defective in H3K9 methylation and improperly upregulated at late developmental stages in the G9a Dkk3 CKO retina. Notably, conditional depletion of G9a in postmitotic photoreceptor precursors (G9a Crx CKO) led to the development of an almost normal retina, indicating that G9a activity mainly in retinal progenitor cells, but not in photoreceptor precursors, is essential for normal terminal differentiation of and survival of the retina. Our results suggest that proper epigenetic marks in progenitor cells are important for subsequent appropriate terminal differentiation and survival of retinal cells by repressing progenitor cell-related genes in differentiating retinal cells.
文献链接：G9a histone methyltransferase activity in retinal progenitors is essential for proper differentiation and survival of mouse retinal cells