Aged Nrf2-Null Mice Develop All Major Types of Age-Related Cataracts

Area of Science:

• Ophthalmology
• Genetics
• Aging Research

Background:

• Age-related cataracts are a leading cause of blindness globally, impacting the majority of older adults.
• Effective treatments to delay cataract onset or progression are needed, necessitating relevant animal models.
• Few animal models accurately recapitulate the diverse types of human cataracts.

Purpose of the Study:

• To investigate the lens phenotypes of aged mice deficient in the antioxidant transcription factor Nfe2l2 (Nrf2 -/-).
• To determine if Nrf2 deficiency leads to cataract development and characterize the types of cataracts formed.
• To evaluate the utility of Nrf2 -/- mice as a model for studying cataractogenesis.

Main Methods:

• Three cohorts of Nrf2 -/- and wild-type C57BL/6J mice were studied.
• Cataracts were assessed using slit lamp imaging, lens photography, and histology.
• Mice were subjected to various dietary conditions, including high/low glycemic diets, regular chow, and caloric restriction.

Main Results:

• Nrf2 -/- mice developed significant cataracts between 11 and 15 months of age.
• Advanced cortical, posterior subcapsular, anterior subcapsular, and nuclear cataracts were observed.
• Histology revealed disrupted fiber cell architecture and retained nuclei in cataractous lenses, with abnormalities appearing by 3 months of age.

Conclusions:

• Nrf2 -/- mice serve as a valuable tool for understanding how impaired antioxidant signaling contributes to various cataract types.
• This model may be instrumental in screening therapeutic agents aimed at preventing or delaying cataractogenesis.
• The findings highlight the role of Nrf2 in maintaining lens health and preventing age-related vision impairment.