Protective effects of estrogen in a rat model of age-related cataracts.
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 methylnitrosourea (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 alpha and beta 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.
Bigsby
R M
RM
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46228, USA. rbigsby@iupui.edu
Cardenas
H
H
Caperell-Grant
A
A
Grubbs
C J
CJ
D000375:Aging; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D004970:Estrone / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007908:Lens, Crystalline / Q000187:drug effects / Q000254:growth & development / Q000473:pathology*; D008770:Methylnitrosourea; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D004343:Drug Implants; D004970:Estrone; D004958:Estradiol; D008770:Methylnitrosourea