1. Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye.
- Author
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Wang CL, Skeie JM, Allamargot C, Goldstein AS, Nishimura DY, Huffman JM, Aldrich BT, Schmidt GA, Teixeira LBC, Kuehn MH, Yorek M, and Greiner MA
- Subjects
- Animals, Male, Rats, Humans, Disease Models, Animal, Anterior Eye Segment pathology, Aqueous Humor metabolism, Cataract pathology, Cataract metabolism, Lens, Crystalline pathology, Lens, Crystalline metabolism, Lens, Crystalline ultrastructure, Ciliary Body pathology, Ciliary Body metabolism, Diet, High-Fat adverse effects, Diabetes Mellitus, Type 2 pathology, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 complications, Rats, Sprague-Dawley, Diabetes Mellitus, Experimental pathology, Diabetes Mellitus, Experimental complications
- Abstract
Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluated changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley rats were fed a high-fat diet (45% fat) or normal diet, and rats fed the high-fat diet were injected with streptozotocin intraperitoneally to generate a model of T2DM. Cataract formation and corneal endothelial cell density were assessed using microscopic analysis. Diabetes-related rat aqueous humor alterations were assessed using metabolomics screening. Transmission electron microscopy was used to assess qualitative ultrastructural changes ciliary process microvessels at the site of aqueous formation in the eyes of diabetic rats and humans. Eyes from the diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes, including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. These results support the use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. All rights reserved.)
- Published
- 2024
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