Quantitative autoradiographic visualization and pharmacology of FP-prostaglandin receptors in human eyes using the novel phosphor-imaging technology

Quantitative autoradiographic visualization of FP prostaglandin receptors was determined in postmortem human eye sections using [H-3]PGF(2 alpha) 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/mm(2)]), iris sphincter muscle (19,261 DLU/mm(2)) and retina (9,544 DLU/mm(2)), with lesser amounts (1,558 - 3,776 DLU/mm(2)) 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 [H-3]PGF(2 alpha) 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 (K-i = 13 - 37 nM), fluprostenol (K-i = 56 - 98 nM), PHXA85 (K-i = 181 - 206 nM) and latanoprost (isopropyl ester of PHXA85; K-i = 0.43 - 4.5 mu M) (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.