PDF(Pubmed)
Abstract：
UNASSIGNED: The purpose of this study was to investigate the ocular morphological characteristics of Col4a3-/- mice as a model of Alport syndrome (AS) and the potential pathogenesis.
UNASSIGNED: The expression of collagen IV at 8, 12, and 21 weeks of age was evaluated by immunohistochemistry in wild-type (WT) and Col4a3-/- mice. Hematoxylin and eosin (H&E) staining and thickness measurements were performed to assess the thickness of anterior lens capsule and retina. Ultrastructure analysis of corneal epithelial basement membrane, anterior lens capsule, internal limiting membrane (ILM), and retinal pigment epithelium (RPE) basement membrane was performed using transmission electron microscopy. Finally, Müller cell activation was evaluated by glial fibrillary acidic protein (GFAP) expression.
UNASSIGNED: Collagen IV was downregulated in the corneal epithelial basement membrane and ILM of Col4a3-/- mice. The hemidesmosomes of Col4a3-/- mice corneal epithelium became flat and less electron-dense than those of the WT group. Compared with those of the WT mice, the anterior lens capsules of Col4a3-/- mice were thinner. Abnormal structure was detected at the ILM Col4a3-/- mice, and the basal folds of the RPE basement membrane in Col4a3-/- mice were thicker and shorter. The retinas of Col4a3-/- mice were thinner than those of WT mice, especially within 1000 µm away from the optic nerve. GFAP expression enhanced in each age group of Col4a3-/- mice.
UNASSIGNED: Our results suggested that Col4a3-/- mice exhibit ocular anomalies similar to patients with AS. Additionally, Müller cells may be involved in AS retinal anomalies.
UNASSIGNED: This animal model could provide an opportunity to understand the underlying mechanisms of AS ocular disorders and to investigate potential new treatments.
UNASSIGNED: The expression of collagen IV at 8, 12, and 21 weeks of age was evaluated by immunohistochemistry in wild-type (WT) and Col4a3-/- mice. Hematoxylin and eosin (H&E) staining and thickness measurements were performed to assess the thickness of anterior lens capsule and retina. Ultrastructure analysis of corneal epithelial basement membrane, anterior lens capsule, internal limiting membrane (ILM), and retinal pigment epithelium (RPE) basement membrane was performed using transmission electron microscopy. Finally, Müller cell activation was evaluated by glial fibrillary acidic protein (GFAP) expression.
UNASSIGNED: Collagen IV was downregulated in the corneal epithelial basement membrane and ILM of Col4a3-/- mice. The hemidesmosomes of Col4a3-/- mice corneal epithelium became flat and less electron-dense than those of the WT group. Compared with those of the WT mice, the anterior lens capsules of Col4a3-/- mice were thinner. Abnormal structure was detected at the ILM Col4a3-/- mice, and the basal folds of the RPE basement membrane in Col4a3-/- mice were thicker and shorter. The retinas of Col4a3-/- mice were thinner than those of WT mice, especially within 1000 µm away from the optic nerve. GFAP expression enhanced in each age group of Col4a3-/- mice.
UNASSIGNED: Our results suggested that Col4a3-/- mice exhibit ocular anomalies similar to patients with AS. Additionally, Müller cells may be involved in AS retinal anomalies.
UNASSIGNED: This animal model could provide an opportunity to understand the underlying mechanisms of AS ocular disorders and to investigate potential new treatments.
摘要：
■这项研究的目的是研究Col4a3-/-小鼠作为Alport综合征（AS）模型的眼部形态学特征以及潜在的发病机理。
■通过免疫组织化学在野生型（WT）和Col4a3-/-小鼠中评估了8、12和21周龄时胶原IV的表达。进行苏木精和伊红(H&E)染色和厚度测量以评估晶状体前囊和视网膜的厚度。角膜上皮基底膜超微结构分析,晶状体前囊,内部限制膜（ILM），和视网膜色素上皮（RPE）基底膜使用透射电子显微镜进行。最后,通过神经胶质原纤维酸性蛋白（GFAP）表达评估Müller细胞活化。
■胶原IV在Col4a3-/-小鼠的角膜上皮基底膜和ILM中下调。Col4a3-/-小鼠角膜上皮的半染色体变得平坦，电子密度低于WT组。与WT小鼠相比，Col4a3-/-小鼠的晶状体前囊较薄。在ILMCol4a3-/-小鼠中检测到异常结构，Col4a3-/-小鼠RPE基底膜的基底褶皱较厚，较短。Col4a3-/-小鼠的视网膜比WT小鼠薄，尤其是离视神经1000微米以内.在Col4a3-/-小鼠的每个年龄组中GFAP表达增强。
■我们的结果表明Col4a3-/-小鼠表现出与AS患者相似的眼部异常。此外,Müller细胞可能与AS视网膜异常有关。
这种动物模型可以为了解AS眼部疾病的潜在机制和研究潜在的新疗法提供机会。
■通过免疫组织化学在野生型（WT）和Col4a3-/-小鼠中评估了8、12和21周龄时胶原IV的表达。进行苏木精和伊红(H&E)染色和厚度测量以评估晶状体前囊和视网膜的厚度。角膜上皮基底膜超微结构分析,晶状体前囊,内部限制膜（ILM），和视网膜色素上皮（RPE）基底膜使用透射电子显微镜进行。最后,通过神经胶质原纤维酸性蛋白（GFAP）表达评估Müller细胞活化。
■胶原IV在Col4a3-/-小鼠的角膜上皮基底膜和ILM中下调。Col4a3-/-小鼠角膜上皮的半染色体变得平坦，电子密度低于WT组。与WT小鼠相比，Col4a3-/-小鼠的晶状体前囊较薄。在ILMCol4a3-/-小鼠中检测到异常结构，Col4a3-/-小鼠RPE基底膜的基底褶皱较厚，较短。Col4a3-/-小鼠的视网膜比WT小鼠薄，尤其是离视神经1000微米以内.在Col4a3-/-小鼠的每个年龄组中GFAP表达增强。
■我们的结果表明Col4a3-/-小鼠表现出与AS患者相似的眼部异常。此外,Müller细胞可能与AS视网膜异常有关。
这种动物模型可以为了解AS眼部疾病的潜在机制和研究潜在的新疗法提供机会。
