Cone Degeneration Following Rod Ablation in a Reversible Model of Retinal Degeneration
Cone Degeneration Following Rod Ablation in a Reversible Model of Retinal Degeneration
复制标题
DOI：
10.1167/iovs.10-5347
复制
发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Zuber, Michael E.
中科院分区：
文献类型：
--
作者：
Choi, Rene Y.;Engbretson, Gustav A.;Zuber, Michael E.
目的.两栖动物视网膜在损伤后再生，使它们成为研究视网膜再生机制的理想动物，但这使它们作为视网膜变性模型的价值受到质疑。作者询问在再生模型非洲爪蟾中杆损失后的初始细胞变化是否与在非再生模型中观察到的相似。他们还询问是否杆损失是可逆的。作者们产生了转基因X。在视杆特异性视紫红质（XOP）启动子的控制下表达大肠杆菌酶硝基还原酶（NTR）的乳杆菌。NTR将抗生素甲硝唑（Mtz）转化为链间DNA交联剂。视觉介导的行为分析和免疫组化被用来确定Mtz对XOPNTR F-1蝌蚪的视觉和视网膜的影响。NTR的表达只在XOPNTR蝌蚪的杆中检测到。Mtz治疗导致视力迅速丧失，到第12天视杆细胞几乎完全消融。视杆细胞消融后，Muller胶质细胞肥大和进行性视锥细胞变性。当动物恢复时，新的杆出生并形成外节。在无杆蝌蚪视网膜中检测到的初始次级细胞变化模拟了在其他视网膜变性模型中观察到的变化。XOPNTR动物中快速和同步的视杆细胞丢失表明该模型可能在视网膜变性的研究中证明是有用的。此外，非洲爪蟾视网膜的再生能力使这些动物成为鉴定具有显著视网膜再生能力的低等脊椎动物中起作用的细胞和分子机制的有价值的工具。（Invest Ophthalmol维斯科学。2011;52：364-373）DOI：10.1167/iovs.10-5347
PURPOSE. Amphibian retinas regenerate after injury, making them ideal for studying the mechanisms of retinal regeneration, but this leaves their value as models of retinal degeneration in question. The authors asked whether the initial cellular changes after rod loss in the regenerative model Xenopus laevis mimic those observed in nonregenerative models. They also asked whether rod loss was reversible.METHODS. The authors generated transgenic X. laevis expressing the Escherichia coli enzyme nitroreductase (NTR) under the control of the rod-specific rhodopsin (XOP) promoter. NTR converts the antibiotic metronidazole (Mtz) into an interstrand DNA cross-linker. A visually mediated behavioral assay and immunohistochemistry were used to determine the effects of Mtz on the vision and retinas of XOPNTR F-1 tadpoles.RESULTS. NTR expression was detected only in the rods of XOPNTR tadpoles. Mtz treatment resulted in rapid vision loss and near complete ablation of rod photoreceptors by day 12. Muller glial cell hypertrophy and progressive cone degeneration followed rod cell ablation. When animals were allowed to recover, new rods were born and formed outer segments.CONCLUSIONS. The initial secondary cellular changes detected in the rodless tadpole retina mimic those observed in other models of retinal degeneration. The rapid and synchronous rod loss in XOPNTR animals suggested this model may prove useful in the study of retinal degeneration. Moreover, the regenerative capacity of the Xenopus retina makes these animals a valuable tool for identifying the cellular and molecular mechanisms at work in lower vertebrates with the remarkable capacity of retinal regeneration. (Invest Ophthalmol Vis Sci. 2011;52:364-373) DOI:10.1167/iovs.10-5347