The ocular microenvironment has evolutionarily adapted several mechanisms of immunosuppression to minimize the induction of inflammation. Neuropeptides produced by the retinal pigment epithelial cells regulate macrophage activity. Two neuropeptides， α-melanocyte-stimulating hormone (α -MSH) and neuropeptide Y (NPY)， are constitutively expressed by the retinal pigment epithelial cells. Together these two neuropeptides induce anti-inflammatory cytokine production in endotoxin-stimulated macrophages and suppress phagocytosis of unopsonized bioparticles. These neuropeptides do not suppress the phagocytosis of opsonized bioparticles; however， they do suppress phagolysosome activation or formation. In this report， we studied the possibility that α-MSH with NPY suppress phagosome maturation within macrophages using opsonized OVA-coated magnetic beads to isolate and analyze the phagosomes. The magnetic bead-containing intercellular vesicles were isolated and assayed for Rab5， Rab7， LAMP1， Ia， and OVA. The macrophages cotreated with α-MSH and NPY were suppressed in Rab7 recruitment to the phagosome with suppression in LAMP1 expression but not in Ia expression. The results demonstrated that the α-MSH/NPY cotreatment suppressed phagosome maturation. In addition， the a-MSH/NPY-cotreated macrophages were suppressed in their ability to Ag stimulate CD4 T cell proliferation. These results imply a potential mechanism of ocular immune privilege to divert Ag processing to prevent autoreactive effector T cells from binding their target cognate Ag within the ocular microenvironment.