Investigating Chemokine-Induced NF-κB Activation in Retinal Cells and Its Contribution to Age-Related Macular Degeneration Pathogenesis: A Systematic Review

Objective To investigate the roles of chemokines in activating the NF-κB signaling pathway in retinal pigment epithelium (RPE) and photoreceptor cells, and their contribution to the pathogenesis of age-related macular degeneration (AMD). Background AMD is a leading cause of vision loss in older adults, driven by chronic inflammation and oxidative stress. The NF-κB transcription factor plays a key role in regulating these processes, with various chemokines, such as CCL2 and CX3CL1, influencing NF-κB activation. Despite advances in treatment, a deeper understanding of how chemokines affect NF-κB activation in RPE and photoreceptor cells remains critical for developing effective therapies. This study seeks to address this gap and improve AMD management. Methods A comprehensive search of databases, including PubMed, MEDLINE, and Google Scholar, was conducted to identify relevant studies on the roles of chemokines in activating NF-κB signaling in RPE and photoreceptor cells. The search covered chemokines such as CCL2 (MCP-1), CX3CL1 (Fractalkine), CCL3 (MIP-1α), CCL5 (RANTES), CXCL8 (IL-8), CXCL10 (IP-10), CXCL1 (GRO-α), CXCL12 (SDF-1), CCL11 (Eotaxin), CXCL16, CXCL9 (MIG), and CXCL11 (I-TAC). Studies were systematically reviewed following PRISMA guidelines to assess the involvement of these chemokines in NF-κB activation. Results The analysis revealed that chemokines, including CCL2, CX3CL1, CCL3, and CCL5, significantly activated NF-κB in RPE and photoreceptor cells, leading to increased inflammation and apoptosis through enhanced cytokine production and reactive oxygen species (ROS) generation. Additionally, CXCL8, CXCL10, CXCL1, and CXCL12 triggered NF-κB activation, contributing to oxidative stress and extracellular matrix (ECM) remodeling, which disrupts retinal structure and function. Other chemokines, such as CCL11, CXCL16, CXCL9, and CXCL11, sustained chronic inflammation and modulated matrix metalloproteinases (MMPs), further implicating them in AMD progression. Conclusion Chemokines, including CCL2, CX3CL1, CCL3, CCL5, CXCL8, CXCL10, CXCL1, CXCL12, CCL11, CXCL16, CXCL9, and CXCL11, activate the NF-κB pathway in RPE and photoreceptor cells, driving chronic inflammation, oxidative stress, and ECM remodeling in AMD. These findings highlight potential therapeutic targets to mitigate disease progression.