Abstract
Abstract: :
Purpose: Engagement of Receptor for Advanced Glycation End products (RAGE) by its ligands, S100/calgranulins and amphoterin, has been implicated in processes linked to cellular motility and invasion. Furthermore, activation of RAGE enhances proinflammatory responses, such as those that occur in diabetic tissues and immune/inflammatory disorders. We hypothesized that ligand-RAGE interaction may contribute to enhanced proinflammatory mechanisms that typify diseases such as proliferative retinopathies. To test this concept, we determined whether the degree of expression of RAGE and its ligands, S100/calgranulins and amphoterin, was increased in the vitreous cavity of human subjects with retinal detachment (RD) due to proliferative diabetic retinopathy (PDR) or proliferative vitreoretinopathy (PVR). Method: Vitreous specimens were obtained from 40 eyes of 40 patients undergoing vitrectomy for traction RD secondary to PDR (n=15) or recurrent RD secondary to PVR (n=15). Control vitreous was retrieved from patients undergoing macular hole (MH) repair (n=10). Immunoblotting using monospecific antibodies to RAGE, S100/calgranulin or amphoterin was performed. Bands were scanned into a densitometer and arbitrary pixel units were determined for each condition (Molecular Dynamics/ImageQuant). Statistical analysis between groups was performed using two-tailed student's t test. Results: Expression of RAGE, S100/calgranulins and amphoterin in the vitreous cavity was significantly increased in subjects with PDR and PVR compared to patients with MH. There were no significant differences in expression of these molecules between subjects with PDR versus PVR. Expression of RAGE, S100/calgranulins and amphoterin in the vitreous cavity Conclusion: Interaction of S100/calgranulins and amphoterin with their signal transduction receptor RAGE may contribute to mechanisms linked to the pathogenesis of proliferative disorders of the retina.
Keywords: 524 proliferative vitreoretinopathy • 388 diabetic retinopathy • 563 retinal detachment