Cytokine-Driven NF-κB Activation in Retinal Cells and Its Impact on the Pathogenesis of Age-Related Macular Degeneration: A Systematic Review

ObjectiveTo investigate the role of cytokine-induced NF-{kappa}B activation in retinal pigment epithelium (RPE) and photoreceptor cells, elucidating its contribution to the pathogenesis of Age-related Macular Degeneration (AMD) and identifying potential therapeutic targets. BackgroundAMD is a leading cause of vision loss in older adults, driven by inflammation, oxidative stress, and immune dysregulation, particularly in RPE and photoreceptor cells. The NF-{kappa}B signaling pathway, activated by cytokines such as TNF-, IL-6, and IL-1{beta}, regulates these pathological processes. Understanding cytokine-induced NF-{kappa}B activation may provide insight into AMD progression and facilitate the development of novel therapeutic strategies. MethodsA systematic review of literature from databases including PubMed, MEDLINE, and Google Scholar was conducted to evaluate the involvement of TNF-, IL-6, IL-1{beta}, IL-8, IFN-{gamma}, IL-17, IL-12, IL-18, IL-33, and IL-25 in activating NF-{kappa}B in RPE and photoreceptor cells, contributing to AMD pathogenesis. The search was performed with no date restrictions and followed PRISMA guidelines. Eligible studies were selected based on predefined criteria assessing NF-{kappa}B activation mechanisms and its effects on inflammation, oxidative stress, and retinal degeneration. ResultsThe investigation revealed that cytokines TNF-, IL-6, IL-1{beta}, IL-8, IFN-{gamma}, IL-17, IL-12, IL-18, IL-33, and IL-25 activate the NF-{kappa}B signaling pathway in retinal pigment epithelium (RPE) and photoreceptor cells. This activation triggers the transcription of genes involved in inflammation, oxidative stress, and immune responses. Chronic NF-{kappa}B activation leads to persistent inflammation, increased oxidative stress, and immune cell recruitment, contributing to retinal cell dysfunction and degeneration. Additionally, NF-{kappa}B-driven upregulation of angiogenic factors such as VEGF promotes neovascularization in wet AMD. These findings highlight the central role of NF-{kappa}B in AMD pathogenesis and suggest that targeting this pathway could mitigate inflammatory and oxidative damage, offering potential therapeutic benefits for AMD patients. ConclusionCytokine-induced NF-{kappa}B activation plays a central role in AMD pathogenesis by promoting chronic inflammation, oxidative stress, and angiogenesis in retinal cells. Targeting NF-{kappa}B could present a therapeutic strategy to reduce inflammatory and oxidative damage, preserving retinal function and preventing vision loss in AMD. Further research is required to develop effective NF-{kappa}B-targeted interventions.