Prostaglandin F(2α) receptors in the human trabecular meshwork

PURPOSE. Prostaglandin F(2α) (PGF(2α)) and analogs, such as latanoprost, are thought to lower intraocular pressure (IOP), primarily by increasing uveoscleral outflow. However, outflow through the trabecular meshwork may be increased as well. The authors hypothesize that any effect on the trabecular meshwork is mediated by prostanoid FP receptors (receptors for prostaglandin F(2α)) in this tissue. METHODS. To test this hypothesis, tissue sections of the human trabecular meshwork and cultures of human trabecular meshwork cells were examined for the presence of FP receptors using immunofluorescence microscopy with affinity-purified antibodies raised against a glutathione-S-transferase (GST)-FP(A) receptor fusion protein. The presence of the receptor was confirmed by using reverse transcription- polymerase chain reaction (RT-PCR), functional assays of PGF(2α)-stimulated inositol phosphate hydrolysis, and intracellular calcium measurements. RESULTS. Positive FP(A) receptor immunolabeling was observed in sections of the human trabecular meshwork and in cultured human trabecular meshwork cells. In both cases, specific labeling could be blocked by preincubation with a GST-FP(A) receptor fusion protein. Cross-blocking experiments with other receptor fusion proteins did not block specific labeling in cultured trabecular meshwork cells. PGF(2α) caused a dose-dependent increase in total inositol phosphate accumulation and intracellular calcium release in human trabecular meshwork cells that was consistent with the presence of FP receptors. Using RT-PCR, message-encoding prostanoid FP(A) receptors were found in total RNA isolated from human trabecular meshwork cells. CONCLUSIONS. Prostanoid FP(A) receptors exist in human trabecular meshwork cells, as shown by the presence of mRNA, protein, and a functional response to PGF(2α). This study indicates that functional FP receptors are present in the human trabecular meshwork and that they may be involved in mediating some of the IOP-lowering effects of PGF(2α) in the eye.