Purpose. Previous work has shown that exposure of lens epithelial cells or rabbit eyes in vivo to ultraviolet B (UVB) radiation enhanced prostaglandin (PG)E2 synthesis. Such enhanced PGE2 synthesis was related to the increased DNA synthesis that followed UVB exposure. The current study examined the relationship between enhanced prostaglandin synthesis and UVB- induced cataract formation. Methods. Seventy albino (New Zealand white) rabbit eyes were exposed to UVB radiation in vivo. Fluence of radiation at the cornea was 2.8 J/cm2, 5.6 J/cm2, or 11.2 J/cm2. Eyes were examined 24 hours after UVB exposure and for as long as 10 days by slit lamp biomicroscopy. Mass spectrometry yeas used to measure PGE2 PGE(2α) and 6-keto- PGF(1α) content of the lens and iris-ciliary body using authentic standards. To determine the effect of inhibition of prostaglandin synthesis on UVB-induced cataract formation, animals were given indomethacin intraperitoneally. Other pharmacologic agents, such as PGE2, PGF(2α) and misoprostol, were applied topically to the eye. The effect of UVB on K+ pump was determined by incubating isolated lenses with [86Rb+]. Results. Twenty-four hours after UVB exposure, PGE2 and PGF(2α) concentrations in aqueous humor were increased by 100- and 30-fold, respectively. Lens PGE2 and PGF(2α) increased by 6- and 4-fold, respectively, after UVB radiation exposure. Pretreatment of animals with indomethacin prevented the rise in lens and aqueous humor PGE2 and PGF(2α) levels. Furthermore, indomethacin was partially protective against UVB cataract formation and lowered cataract severity from stage 3 to stage 1, but it did not prevent UVB-induced lens changes completely. Topical application of PGE2 before UVB exposure completely prevented cataract formation in the LWB-exposed eye. In contrast, topical administration of PGF(2α) increased cataract severity. UWB-induced cataract formation preceded changes in [86Rb]+ uptake in lenses subsequently incubated in K+-free Tyrode's. Conclusions. Enhanced synthesis of cyclooxygenase products of arachidonic acid metabolism in the lens is associated with UVB-induced cataract formation in albino rabbit eyes, and inhibition of cyclooxygenase by indomethacin decreased the severity of cataracts. PGE2, the principal arachidonic acid metabolite, appears to have a protective role because pretreatment of the eye with topical PGE2 completely prevented LWB- induced cataract formation, whereas PGF(2α) increased the severity of the cataract. The evidence presented for a role of PGF(2α) in the development of cataract suggests that caution be exercised in the use of PGF(2α) derivatives in the therapy of glaucoma.
|Number of pages||10|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Jul 1996|