Differential Transcription Factor Activator Protein-2 Delta Genotypes Affect the Levels of Interleukin-1 Beta, Interleukin 8, and Vascular Endothelial Growth Factor-C in the Retinal Pigment Epithelial Cells after Long-term Light Exposure.

Retinal degeneration accompanied by abnormal neovascularization from the choroid in the macular area is a critical disease to cure. Retinal cell apoptosis or inflammation in the macula can lead to neovascularization in that area. Some environmental factors such as long-term light exposure, particularly the blue end of the light spectrum, can damage the retina, causing such a disease. Improved understanding of genetic molecules has indicated that certain genes may be potential biomarkers of neovascular macular degeneration. This study aimed to investigate the expression of transcription factor activator protein-2 δ (TFAP-2D) in the retina and explore its role in the pathogenesis of retinal degeneration. For this, a long-term light exposure animal model was used to evaluate TFAP-2D expression in the retina. In addition, two vectors overexpressing different genotypes of TFAP-2D were transfected into retinal pigment epithelial (RPE) cells, and the expression of angiogenesis molecules was investigated. It was found that TFAP-2D expression was observed in the RPE area of the retina in long-term light-exposed rats; however, no TFAP-2D expression was detected in the retina of control (normal) rats. Interleukins (ILs) 1B, IL8, vascular endothelial growth factor (VEGF)-C, and one VEGF receptor (kinase insert domain receptor) were significantly upregulated in RPE cells with TFAP-2D with a C allele at rs78648104 (TFAP-2D-C) overexpression. In conclusion, experiments with different TFAP-2D genotypes revealed that long-term light exposure upregulated TFAP-2D expression in the RPE cells of the retina. In addition, overexpression of TFAP-2D-C induced the release of IL1B, IL8, and VEGF-C, which may lead to neovascularization in the choroid and retina.