Aged Nrf2-Null Mice Develop All Major Types of Age-Related Cataracts
| Autor: | Sheldon Rowan, Shuhong Jiang, Sarah G. Francisco, Laura C. D. Pomatto, Zhiwei Ma, Xiaodong Jiao, Maria M. Campos, Sandeep Aryal, Shaili D. Patel, Binapani Mahaling, S. Amer Riazuddin, Elia J. Duh, Salil A. Lachke, J. Fielding Hejtmancik, Rafael de Cabo, Paul G. FitzGerald, Allen Taylor |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Aging antioxidant genetic structures NF-E2-Related Factor 2 Knockout Inbred C57BL Slit Lamp Microscopy Ophthalmology & Optometry Medical and Health Sciences Cataract Lens Mice Lens Crystalline Genetics Animals Eye Disease and Disorders of Vision Nutrition Mice Knockout Crystalline Animal Prevention Cell Differentiation Biological Sciences eye diseases Diet Mice Inbred C57BL Disease Models Animal nutrition Glucose Phenotype Glycemic Index Disease Models Female sense organs caloric restriction age-related cataract |
| Zdroj: | Investigative ophthalmology & visual science, vol 62, iss 15 Investigative Ophthalmology & Visual Science |
| Popis: | Purpose Age-related cataracts affect the majority of older adults and are a leading cause of blindness worldwide. Treatments that delay cataract onset or severity have the potential to delay cataract surgery, but require relevant animal models that recapitulate the major types of cataracts for their development. Unfortunately, few such models are available. Here, we report the lens phenotypes of aged mice lacking the critical antioxidant transcription factor Nfe2l2 (designated as Nrf2 −/−). Methods Three independent cohorts of Nrf2 −/− and wild-type C57BL/6J mice were evaluated for cataracts using combinations of slit lamp imaging, photography of freshly dissected lenses, and histology. Mice were fed high glycemic diets, low glycemic diets, regular chow ad libitum, or regular chow with 30% caloric restriction. Results Nrf2 −/− mice developed significant opacities between 11 and 15 months and developed advanced cortical, posterior subcapsular, anterior subcapsular, and nuclear cataracts. Cataracts occurred similarly in male mice fed high or low glycemic diets, and were also observed in 21-month male and female Nrf2 −/− mice fed ad libitum or 30% caloric restriction. Histological observation of 18-month cataractous lenses revealed significant disruption to fiber cell architecture and the retention of nuclei throughout the cortical region of the lens. However, fiber cell denucleation and initiation of lens differentiation was normal at birth, with the first abnormalities observed at 3 months. Conclusions Nrf2 −/− mice offer a tool to understand how defective antioxidant signaling causes multiple forms of cataract and may be useful for screening drugs to prevent or delay cataractogenesis in susceptible adults. |
| Databáze: | OpenAIRE |
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