Platelet-derived growth factor ligands and receptors immunolocalized in proliferative retinal diseases

Abstract

Purpose: Platelet-derived growth factor (PDGF) and its receptors could contribute to the development of proliferative retinal membranes, because PDGF is angiogenic and is both mitogenic and chemotactic for retinal pigment epithelial (RPE) and glial cells, components of membranes. The authors sought to determine whether PDGF ligands and their receptors were present in proliferative retinal membranes.

Methods: To localize PDGF ligands and receptors, the authors examined normal postmortem control retinas, intact eyes with proliferative vitreoretinopathy (PVR) or proliferative diabetic retinopathy (PDR), and membranes removed by vitrectomy from patients with PVR, epimacular proliferation, PDR, or PVR with PDR of previous onset. Sections were stained with antibodies specific for each PDGF ligand and receptor, using an avidin-biotin-complex immunohistochemical technique. To correlate PDGF receptor beta (PDGFR beta) and ligand immunostaining, sections were doubled labelled with antibodies specific for either PDGF-A or PDGF-B.

Results: Ligands. In the normal retina and choroid, staining for the A-chain was limited to vascular cells. Only the nerve fiber layer and vessels were positive for the B-chain. In diseased tissue, PDGF-A immunoreactivity was detected as intense staining ( ) of all but one of the proliferative retinal membranes; some RPE cells were positive for PDGF-A, especially in the eye with PDR. PDGF-B was also present in many proliferative retinal membranes but not in RPE cells. Receptors. In the normal retina and choroid, both PDGFR alpha and PDGFR beta were detected only in vessels. In proliferative retinal membranes, both receptors were detected in vessels. Long strands of RPE-like cells at the edges of PVR membranes were strongly positive for PDGFR beta but negative or +/-, respectively, for PDGFR alpha. Double-label assays showed that PDGFR beta was often colocalized with each PDGF ligand, especially in pigmented cells.

Conclusions: PDGF ligands and receptors are widespread in proliferative retinal membranes of different origin. Because PDGFR beta and PDGF-B were colocalized in many of the same cells, the potential for autocrine and paracrine stimulation of cell migration and growth exists. These results are consistent with a role for PDGF ligands and receptors in the pathogenesis of different proliferative retinopathies.