Bennett J, Tanabe T, Sun D, Zeng Y, Kjeldbye H, Gouras P, Maguire A M
Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA.
Nat Med. 1996 Jun;2(6):649-54. doi: 10.1038/nm0696-649.
Mutations in the beta subunit of the cGMP phosphodiesterase gene (beta PDE) can cause a recessively inherited retinal degeneration in several species, including mice, dogs and humans. We tested the possibility of altering the course of retinal degeneration in the rd mouse through subretinal injection of a recombinant replication-defective adenovirus that contains the murine cDNA for wild-type (beta PDE, Ad.CMV beta PDE. Subretinal injection of Ad.CMV beta PDE results in beta PDE transcripts and increased PDE activity and delays photoreceptor cell death by six weeks. The findings demonstrate cell rescue by in vivo gene transfer, thus supporting the feasibility of treating an inherited retinal degeneration by somatic gene therapy.
环磷酸鸟苷磷酸二酯酶基因（β-PDE）β亚基的突变可在包括小鼠、狗和人类在内的多个物种中引发隐性遗传的视网膜变性。我们通过视网膜下注射一种重组复制缺陷型腺病毒来测试改变rd小鼠视网膜变性进程的可能性，该腺病毒含有野生型小鼠β-PDE的互补DNA（Ad.CMV β-PDE）。视网膜下注射Ad.CMV β-PDE可产生β-PDE转录本，增加磷酸二酯酶活性，并将光感受器细胞死亡延迟六周。这些发现证明了体内基因转移可实现细胞拯救，从而支持了通过体细胞基因疗法治疗遗传性视网膜变性的可行性。
