Isoflurane Induces Neurodegenerative Changes in Retinal Pigment Epithelial Cells

Background: Inhaled anesthetics have the potential to induce neurons to undergo cellular changes seen in Alzheimer's disease. Given the similarities between Alzheimer's disease and age-related macular degeneration (AMD), we propose that similar changes might be observed in retinal cells exposed to isoflurane. Methods: Human derived retinal pigment epithelial cells (ARPE-19) were exposed to 1.2% and 3.5% isoflurane for four hours. Markers of apoptosis and cellular inflammation within the lysate of isoflurane exposed cells and control cells were measured using a luminometer. Transcript levels of genes involved in apoptosis, cell cycle entry and progression, and the formation of β-amyloid plaque were measured using real time PCR. Results: Isoflurane exposed cells had increased levels of reactive oxygen species (ROS/RNS) and caspases 3 and 7 as determined by a luminometer. Isoflurane treated cells demonstrated significant increases in transcription of several genes linked to the formation of β-amyloid, including BACE1, APPBP1, APPBP2, APH1A, APH1B and NCSTN. Significant increases in transcription of cell cycle markers POLD1, MDM2, CCNA2 and RBL2 were observed, as was an increase in the transcription of JUN which is the first marker for apoptosis cascade. Conclusions: ARPE-19 cells that were exposed to isoflurane in vitro displayed many changes that have been associated with the development of neurodegenerative disease. A potential link between isoflurane exposure and the development of AMD should be further explored.