Quantitative autoradiographic visualization and pharmacology of FP-prostaglandin receptors in human eyes using the...

Quantitative autoradiographic visualization of FP prostaglandin receptors was determined in postmortem human eye sections using [3H]PGF2alpha and the novel phosphor-imaging technology coupled with computerized image analysis. Densitometric analysis of digital images obtained after a 19-day screen-exposure revealed FP receptors to be highly concentrated in the longitudinal ciliary muscle (12,741 digital light units [DLU/mm2]), iris sphincter muscle (19,261 DLU/mm2) and retina (9,544 DLU/mm2), with lesser amounts (1,558-3,776 DLU/mm2) in five other ocular structures (n = 3-4 donors). The highest percentage specific binding was in the iris sphincter and longitudinal ciliary muscle (78-73%) and lowest in the lens (12%). Binding of [3H]PGF2alpha to the longitudinal ciliary and iris sphincter muscles and retina was concentration-dependently and potently displaced by known FP-receptor-selective compounds such as cloprostenol (Ki = 13-37 nM), fluprostenol (Ki = 56-98 nM), PHXA85 (Ki = 181-206 nM) and latanoprost (isopropyl ester of PHXA85; Ki = 0.43-4.5 microM) (from up to 4 donor eyes). These quantitative phosphor-imaging autoradiography data provide further evidence for the presence of FP receptors in human longitudinal ciliary muscle, one of the tissues involved in the intraocular pressure lowering effects of FP-class prostaglandins. The quantitative localization of FP receptors in the human iris, iris sphincter muscle, and retina represent interesting new observations.