Van Hooser J P, Aleman T S, He Y G, Cideciyan A V, Kuksa V, Pittler S J, Stone E M, Jacobson S G, Palczewski K
Departments of Ophthalmology, Chemistry, and Pharmacology, University of Washington, Seattle, WA 98195, USA.
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8623-8. doi: 10.1073/pnas.150236297.
Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal degenerations known as Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congenital amaurosis, have no rod photopigment and severely impaired rod physiology. We analyzed retinoid flow in this model and then intervened by using oral 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h, there was formation of rod photopigment and dramatic improvement in rod physiology, thus demonstrating that mechanism-based pharmacological intervention has the potential to restore vision in otherwise incurable genetic retinal degenerations.
编码RPE65的视网膜色素上皮基因突变是导致无法治愈的早发性隐性人类视网膜变性（即莱伯先天性黑蒙）的一个原因。Rpe65基因缺陷小鼠是莱伯先天性黑蒙的一种模型，它们没有视杆光色素，并且视杆生理功能严重受损。我们分析了该模型中的类视黄醇流动，然后通过口服9-顺式视黄醛进行干预，试图绕过由基因异常导致的生化障碍。在48小时内，视杆光色素形成，视杆生理功能显著改善，从而证明基于机制的药物干预有可能恢复其他无法治愈的遗传性视网膜变性患者的视力。
