Inflammatory Cytokines Modulated by Beta-Adrenergic Receptors in Retinal Muller Cells

Abstract

Purpose:: To determine if ß-adrenergic receptors are involved in the regulation of inflammatory cytokines in Muller cells in a hyperglycemic environment.

Methods:: Real-time polymerase chain reaction was carried out to measure steady-state mRNA expression for the following inflammatory markers: iNOS, TNFα, Il-1ß, and ICAM1. Western blot analysis and ELISA assays were performed to determine the protein expression of these inflammatory markers and PGE₂.

Results:: Isoproterenol significantly decreased protein levels of iNOS, TNFα, and Il-1ß in cells treated with high glucose as early as one hour, compared to cells with no treatment. There were no significant changes observed in protein levels of ICAM1 and PGE₂. Steady-state mRNA levels for iNOS were significantly decreased after one hour, whereas ICAM1 gene expression was significantly increased after one hour. Gene expression of Il-1ß was significantly increased after six hours of treatment, whereas TNFα showed no significant changes in steady-state mRNA levels.

Conclusions:: These results suggest that adrenergic receptors are involved in the increase in protein levels of TNFα, IL-1ß, and both gene expression and protein levels of iNOS. ß-adrenergic receptor agonists had no effect on PGE₂ levels. Overall, agonists to ß-adrenergic receptor signaling may alleviate some of the increased cytokine release noted in diabetic retinopathy.

Keywords: diabetic retinopathy • Muller cells • inflammation