RPE65 is present in human green/red cones and promotes photopigment regeneration in an in vitro cone cell model.
RPE65 is present in human green/red cones and promotes photopigment regeneration in an in vitro cone cell model.
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DOI：
10.1523/jneurosci.4265-11.2011
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发表时间：
2011-12-14
期刊：
影响因子：
--
通讯作者：
Crouch RK
中科院分区：
文献类型：
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作者：
Tang PH;Buhusi MC;Ma JX;Crouch RK
RPE65 是眼睛视网膜色素上皮 (RPE) 中表达丰富的蛋白质，是类视黄醇代谢支持视力所必需的。其基因突变与先天性疾病 Leber 先天性黑蒙 2 型 (LCA2) 相关，其特征是早期出现中央视力丧失。目前的基因治疗试验以恢复这些患者 RPE 内的功能性 RPE65 为目标，并取得了一些成功。最近的数据显示，RPE65 也存在于小鼠视锥体内，可促进功能。在这项研究中，我们评估了 RPE65 在人类视锥细胞中的存在，并研究了其在 661W 视锥细胞系中支持视锥细胞功能的潜在机制。我们发现 RPE65 在人绿色/红色视锥细胞中选择性表达，但在蓝色视锥细胞中不存在，并介导体外感光色素合成的酯水解。这些数据表明锥体 RPE65 支持人类昼间视力，可能增强我们治疗 LCA2 的策略。
RPE65 is an abundantly expressed protein within the retinal pigment epithelium (RPE) of the eye that is required for retinoid metabolism to support vision. Its genetic mutations are linked to the congenital disease Leber congenital amaurosis Type 2 (LCA2) characterized by the early onset of central vision loss. Current gene therapy trials have targeted restoration of functional RPE65 within the RPE of these patients with some success. Recent data show RPE65 is also present within mouse cones to promote function. In this study, we evaluated the presence of RPE65 in human cones and investigated its potential mechanism for supporting cone function in the 661W cone cell line. We found that RPE65 was selectively expressed in human green/red cones but absent from blue cones and mediated ester hydrolysis for photopigment synthesis in vitro. These data suggest that cone RPE65 supports human diurnal vision, potentially enhancing our strategies for treating LCA2.