Visualization of sigma1 receptors in eyes by ex vivo autoradiography and in vivo positron emission tomography.

Sigma receptors are present on the neurons of the central nervous system and in peripheral organs. They have also been demonstrated in ocular tissues by in vitro membrane binding assays. We have investigated whether sigma(1) receptors can be demonstrated in rat eyes by ex vivo autoradiography using [(11)C]SA4503, a selective radioligand. We also tested whether in vivo positron emission tomography (PET) can be used to show sigma(1) receptors in rabbit eyes. In rats, a high accumulation of [(11)C]SA4503 was found in the iris-ciliary body and retina. A carrier-loading experiment showed that the receptor-specific binding of [(11)C]SA4503 was approximately 75% of the total binding in the brain. Sigma(1) receptors were also detected in the projecting terminals of the retina to the superior colliculus. PET showed radioactivity in the anterior segment including the iris-ciliary body and retina, and pretreatment or displacement by a sigma receptor ligand (haloperidol), suggested that the PET signal reflects radioligand-receptor binding. The high density of sigma(1) receptors in the iris-ciliary body and retina was confirmed by ex vivo autoradiography. In conclusion, the iris-ciliary body and retina are rich in sigma(1) receptors, and PET may be used to investigate the in vivo distribution of these neuroreceptors in the eye.