Title : N-Acetylcysteine as a neuroprotective agent: Combating oxidative stress in retinal degeneration

Background: Oxidative stress plays a central role in damaging retinal pigment epithelium (RPE) cells, a characteristic of retinal degenerative diseases. Sodium iodate (NaIO?), a potent oxidative agent which selectively targets RPE cells, making it a potential retinal degeneration disease model. The current study investigates the therapeutic potential of N-Acetylcysteine (NAC), a well-known antioxidant, in counteracting NaIO? induced oxidative damage in RPE cells.

Methods: Using ARPE-19 cells, we evaluated protective efficiency of NAC through a comprehensive analysis of cell viability, reactive oxygen species (ROS) production, mitochondrial membrane potential, colony forming ability, cell migration, cell cycle distribution, and gene expression related to oxidative stress, inflammation, autophagy, and cell cycle regulation.

Results: Exposure to NaIO? activated a cascade of cellular dysfunctions in ARPE-19 cells, including increased ROS production, reduced mitochondrial membrane potential, and weakened proliferative and migratory capacities as well as significant dysregulation of genes associated with cellular stress responses. Moreover, treatment with NAC effectively restored these effects by lowering ROS levels, restoring mitochondrial membrane potential, improving cell viability, and maintaining colony forming and migration ability. NAC also inhibited apoptosis and normalized the expression of genes involved in oxidative stress (OS), inflammation, and autophagy.

Conclusion: Our findings determine role of NAC against oxidative stress in RPE cells and highlight its potential as a therapeutic approach to combat oxidative stress driven retinal degeneration.

Kainat Ahmed holds an M.Phil in Molecular Medicine from the Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS) at the University of Karachi, Pakistan. Her graduate research focused on developing extracellular matrix (ECM)-based bioscaffolds derived from human amnion membrane, aimed at promoting tissue repair and advancing regenerative medicine. In 2025, she joined the Department of Ophthalmology & Visual Sciences at Aga Khan University as a Research Associate. Her current work explores cutting-edge stem cell–based therapies for vision restoration in ocular diseases, with a particular emphasis on glaucoma. Kainat has authored five publications, including three peer-reviewed research articles with a cumulative impact factor of 10.8, and two book chapters contributing to the field of molecular and regenerative medicine.