Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Invest Ophthalmol Vis Sci. 2011 Jun 13;52(7):4200-7. doi: 10.1167/iovs.10-6434.
The bugeye mutant has an enlarged eye phenotype, presumably because of elevated intraocular pressure. Since elevated intraocular pressure is a significant risk factor for glaucoma, the bugeye zebrafish mutant may be a model organism for the disease.
The optomotor response (OMR) was used to assess visual responsiveness in both larval and adult zebrafish. Electroretinograms (ERGs) were recorded to measure outer retinal function, and histologic analyses were performed on WT and mutant eyes.
At 5 days old, bugeye mutants have an OMR, ERGs, and retinal morphology indistinguishable from those of wild-type (WT) animals. By 2 months of age, bugeye mutants begin to develop an enlarged eye phenotype. At 3 months, some mutants show deficits in the OMR assay, including lower contrast sensitivity. The data suggest that there is a correlation between the size of the enlarged eye and the degree of OMR deficit. Histologic analysis of the bugeye mutant retina revealed decreases in retinal ganglion cell densities by 3 months. By 5 months, the mutant's ERG b-wave had smaller amplitudes and longer latencies at brighter light intensities than those of the WT fish.
After phenotypic onset at 3 months, the bugeye mutants begin to develop visual deficits. At 3 months, bugeye mutants exhibit a decrease in retinal cell densities and by 5 months, they show diminished outer retinal function. In summary, the bugeye mutant provides a means of studying glaucoma-associated phenotypes in the zebrafish.
大眼突变体具有眼睛增大的表型，推测是因为眼内压升高。由于眼内压升高是青光眼的一个重要危险因素，大眼斑马鱼突变体可能是该疾病的一种模型生物。
使用光感受器反应（OMR）来评估幼鱼和成年斑马鱼的视觉反应能力。记录视网膜电图（ERG）以测量外视网膜功能，并对 WT 和突变体眼睛进行组织学分析。
在 5 天时，大眼突变体的 OMR、ERG 和视网膜形态与 WT 动物无异。在 2 个月大时，大眼突变体开始出现眼睛增大的表型。在 3 个月时，一些突变体在 OMR 测定中表现出缺陷，包括对比度敏感性降低。数据表明，眼睛增大的程度与 OMR 缺陷的程度之间存在相关性。对大眼突变体视网膜的组织学分析显示，视网膜神经节细胞密度在 3 个月时下降。在 5 个月时，与 WT 鱼相比，突变体的 ERG b 波在更亮的光强下振幅更小，潜伏期更长。
在 3 个月出现表型后，大眼突变体开始出现视觉缺陷。在 3 个月时，大眼突变体表现出视网膜细胞密度降低，在 5 个月时，它们显示出外视网膜功能减弱。总之，大眼突变体为研究斑马鱼中与青光眼相关的表型提供了一种手段。
