The α7 nicotinic receptor in retinal pigment epithelium: Exploring a new pharmacological target

Abstract

The α7 nicotinic acetylcholine receptor is highly expressed in the brain and also found in non-neuronal cells, including epithelial and immune cells. It contributes to cognition, memory, neuroprotection, and inflammation regulation, and is increasingly studied as a therapeutic target in neurodegenerative and inflammatory disorders. The retinal pigment epithelium (RPE) supports photoreceptor function and maintains the outer blood-retinal barrier. RPE dysfunction is implicated in age-related macular degeneration (AMD), in which oxidative stress drives inflammation. Evidence suggests α7 is ex- pressed in RPE, but its role remains unclear. We investigated α7 in the D407 cell line, a model of RPE cells. Using real-time PCR, immunofluorescence with anti-α7 antibody or alpha-bungarotoxin, confocal microscopy, and flow cytometry, we confirmed α7 expres- sion. Notably, α7 cell distribution changed upon exposure to stress- ors such as ferric ammonium citrate (FAC) or β-amyloid. Functional activity was confirmed using fluo-4AM, showing a 3-fold increase in intracellular calcium following α7 stimulation. FAC-induced oxi- dative stress elevated reactive oxygen species (ROS), measured with DCFH- DA, but preincubation with an α7 agonist significantly reduced ROS levels. This study characterizes α7 in D407 cells and reveals its dynamic localization and protective role under oxidative stress. These findings support further exploration of α7 as a therapeutic target in retinal neurodegeneration.