Interactive Expressions of HtrA1 and VEGF in Human Vitreous Humors and Fetal RPE Cells

PURPOSE. High-temperature requirement factor A1 (HtrA1) is associated with exudative age-related macular degeneration, an angiogenic retinal disease related to vascular endothelial growth factor (VEGF). This study investigates the interactive relationship between the expressions of HtrA1 and VEGF. METHODS. The vitreous humor levels of HtrA1, VEGF, and pigment epithelium-derived factor were determined in 55 unrelated Han Chinese patients who underwent ocular surgeries. Expressions of HTRA1 and VEGFA were studied interactively and under stress conditions in primary human fetal retinal pigment epithelial (RPE) cells to evaluate their regulations. RESULTS. Vitreous levels of HtrA1 were significantly associated with that of VEGF in vitreous samples from all patients (Pearson's correlation coefficient test, r = 0.650, P = 7.91 x 10(-8)) and from patients with retinal detachment (r = 0.835, P = 2.14 x 10(-7)). On stress induction, HTRA1 and VEGFA were upregulated in human fetal RPE cells treated by tunicamycin and dithiothreitol, but reduced after treatment by MG132. However, HtrA1 and VEGF did not regulate each other in their expressions. CONCLUSIONS. This study revealed an association between HtrA1 and VEGF in human vitreous humors and RPE cells. They are both related to stress and inflammatory conditions. (Invest Ophthalmol Vis Sci. 2011;52:3706-3712) DOI: 10.1167/iovs.10-6773