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Col4a3-/- 小鼠眼部形态特征分析及其作为 Alport 综合征小鼠模型的研究。

Characterization of Ocular Morphology in Col4a3-/- Mice as a Murine Model for Alport Syndrome.

机构信息

Department of Ophthalmology, Peking University First Hospital, Xicheng District, Beijing, China.

Department of Pediatrics, Peking University First Hospital, Xicheng District, Beijing, China.

出版信息

Transl Vis Sci Technol. 2024 Jul 1;13(7):16. doi: 10.1167/tvst.13.7.16.

DOI:10.1167/tvst.13.7.16
PMID:39042048
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11268448/
Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

Our results suggested that Col4a3-/- mice exhibit ocular anomalies similar to patients with AS. Additionally, Müller cells may be involved in AS retinal anomalies.

TRANSLATIONAL RELEVANCE

This animal model could provide an opportunity to understand the underlying mechanisms of AS ocular disorders and to investigate potential new treatments.

摘要

目的

本研究旨在探讨 Col4a3-/- 小鼠作为 Alport 综合征 (AS) 模型的眼部形态特征及其潜在发病机制。

方法

采用免疫组织化学法检测野生型 (WT) 和 Col4a3-/- 小鼠在 8、12 和 21 周龄时的胶原 IV 表达情况。采用苏木精和伊红 (H&E) 染色及厚度测量法评估前晶状体囊和视网膜的厚度。采用透射电镜观察角膜上皮基底膜、前晶状体囊、内界膜 (ILM) 和视网膜色素上皮 (RPE) 基底膜的超微结构。最后，通过胶质纤维酸性蛋白 (GFAP) 表达评估 Müller 细胞的激活情况。

结果

Col4a3-/- 小鼠角膜上皮基底膜和 ILM 中的胶原 IV 表达下调。Col4a3-/- 小鼠角膜上皮半桥粒变得平坦，电子密度较 WT 组降低。与 WT 小鼠相比，Col4a3-/- 小鼠的前晶状体囊更薄。Col4a3-/- 小鼠的 ILM 出现异常结构，RPE 基底膜的基底部褶皱更厚且更短。Col4a3-/- 小鼠的视网膜比 WT 小鼠薄，尤其是在距视神经 1000 µm 以内的区域。各年龄段 Col4a3-/- 小鼠的 GFAP 表达增强。

结论

本研究结果表明，Col4a3-/- 小鼠表现出与 AS 患者相似的眼部异常，Müller 细胞可能参与 AS 视网膜异常。

翻译

朱利安

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/541ec7171ff4/tvst-13-7-16-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/393acef515e6/tvst-13-7-16-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/89c47351f814/tvst-13-7-16-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/1f875f91ca64/tvst-13-7-16-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/c80e700e4ced/tvst-13-7-16-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/049fe6c9159a/tvst-13-7-16-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/ec11aaa4a5e9/tvst-13-7-16-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/541ec7171ff4/tvst-13-7-16-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/393acef515e6/tvst-13-7-16-f001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f4f/11268448/541ec7171ff4/tvst-13-7-16-f007.jpg

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