Quantitative Autoradiographic Visualization and Pharmacology of FP-Prostaglandin Receptors in Human Eyes Using the Novel Phosphor-Imaging Technology

ABSTRACT

Quantitative autoradiographic visualization of FP prostaglandin receptors was determined in postmortem human eye sections using [³H]PGF_2α 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]PGF_2α 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 μM) (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.