Protective effects of estrogen in a rat model of age-related cataracts

Robert M. Bigsby, Horacio Cardenas, Andrea Caperell-Grant, Clinton J. Grubbs

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Abstract

Women have a higher incidence of cataracts, and epidemiologic data suggest that the increased risk may be caused by a lack of estrogen in postmenopausal years. We have examined the effects of estrogen on methyinitrosourea (MNU)-induced cataractogenesis in Sprague-Dawley rats. Animals were ovariectomized, injected with MNU, and treated with estradiol or estrone by a continuous-release, subcutaneous Silastic implant, or they received an empty Silastic implant (no hormone). In the no-hormone group, rats developed opaque lenses approximately 6 months after MNU treatment. By 8 months, 74% (14/19) of the no-hormone rats had evident opacity in one or both eyes by simple gross inspection; 58% (22/38) of the eyes in this group were opaque. Estradiol or estrone treatment reduced the incidence of cataractous eyes to 12% or 25%, respectively. Lenses were examined under a dissecting microscope for light transmission. The lenses of the group treated with no hormone had light transmission of 26% ± 9.2%, whereas lenses from the estradiol-treated animals had light transmission of 72% ± 5.8%. Histological examination revealed that the anterior cortices of the opaque lenses were disrupted and showed the hallmark signs of age-related cataracts; in addition, some eyes that appeared clear by macroscopic examination showed the early histologic signs of cataractogenesis. It was demonstrated with reverse transcription-PCR that lens cells express both α and β types of estrogen receptor, suggesting that the protective effects of the hormones may be a direct, receptor-mediated phenomenon. Thus, the MNU-treated, ovariectomized rat serves as a model for age-related cataractogenesis, and observation of a clear protective effect of estrogens in this system supports the implications of epidemiologic data.

Original languageEnglish (US)
Pages (from-to)9328-9332
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number16
DOIs
StatePublished - Aug 3 1999

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