In summary, our investigation reveals that deficiency of CXCR5 abrogates CXCL13/CXCR5 signaling and this alters the normal PI3K-Akt signaling pathway, FoxO signaling pathway, mTOR signaling pathway, focal adhesion, endocytosis, ubiquitin-mediated proteolysis, TNF-alpha NF-kB signaling pathway, adipogenesis genes, p53 signaling, Ras pathway, autophagy, epithelial–mesenchymal transition (EMT), and mitochondrial pathways, leading to dysregulated RPE functioning, which may result in retinal degeneration that is observed in vivo [5,8,9]. Here, TNF is linked to retinal degeneration.