Expression and localization of FP and EP prostanoid receptor subtypes in human ocular tissues

Abstract

PURPOSE. To determine the expression and precise cellular and subcellular localization of the EP prostanoid receptor subtypes EP1 through EP4 and the FP receptor in normal human ocular tissues on the protein and mRNA levels. METHODS. Expression of EP and FP receptor proteins was examined by immunohistochemistry on the light microscopic level, using subtype-specific antibodies on frozen and paraffinembedded tissue sections of 10 normal human donor eyes. The subcellular distribution of the receptor proteins was studied by electron microscopic immunogold labeling, mRNA expression in various ocular tissues was analyzed by reverse transcriptionpolymerase chain reaction, using subtypespecific primers. RESULTS. The highest expression of the EP1 receptor protein was found in the epithelia of the cornea, conjunctiva, lens, and the ciliary body; trabecular cells; iris vessels; and retinal ganglion cells. EP2 receptor labeling was most prominent in the corneal epithelium and choriocapillaries. EP3 and EP4 receptor labeling was primarily observed in the corneal endothelium and keratocytes, trabecular cells, ciliary epithelium, and conjunctival and iridal stroma cells, and EP3 was found, in addition, in retinal Müller cells. The highest expression of FP receptor protein was found in the corneal epithelium, ciliary epithelium, the circular portion of ciliary muscle, and iris stromal and smooth muscle cells. Immunoelectron microscopy showed a subcellular distribution of all prostanoid receptors along plasma membranes and the nuclear envelope. EP and FP receptor mRNA expression largely paralleled the proteins' expression patterns. CONCLUSIONS. The findings demonstrate a wide distribution but differential expression of FP and EP prostanoid receptor sub-types in human ocular tissues. EP1 through EP4 receptor sub-type expression in human outflow pathways could be significant for future pharmacologic management strategies for the glaucomas.