老年性黃斑部病變是造成老年族群失明主因，導致不可逆的中央視力喪失。老年性黃斑部病變的病因非常複雜，基因缺陷、代謝功能與環境因子間的交互作用會慢性地導致老年性黃斑部病變。在疾病的發展過程中，視網膜色素上皮細胞的氧化壓力上升常認為是病變的關鍵，因此，本研究聚焦在一種誘發氧化壓力的環境因子：多環芳香烴碳氫化合物 (polycyclic aromatic hydrocarbons, PAHs)。隨著焚燒大量的城市固體廢棄物，在焚化爐中的不完全燃燒會產生PAHs，PAHs便隨著可吸入性的飛灰粒子被排放到環境中，並且，PAHs具有相當的生物累積性以及高度脂溶性，可能會隨著食物攝入或吸入性粒子暴露到人體中。為了研究吸入性飛灰中多環芳香烴對老年性黃斑部病變的影響，利用DLPI將吸入性飛灰PM2.5-1(直徑2.5-1微米) 由城市廢棄物焚燒飛灰樣品中分離出來，其占總飛灰0.128%(w/w)，藉GC-MS定量總多環芳香烴碳氫化合物含量為11.3 ppm。將PM2.5-1及PAHs分別暴露到ARPE-19細胞中，皆引發顯著的氧化壓力上升。此外，在跨上皮電阻測量結果中發現，PM2.5-1及PAH皆會減少ARPE-19細胞層的跨膜電阻，利用免疫螢光染色發現，單層細胞間的緊密連接蛋白ZO-1明顯受到破壞，而導致穿透性上升。進一步地，利用qPCR檢驗暴露PAH後基因表現量的變化，結果導致CCL2、CRP、CXCL1、CXCL12、ITGB2、MMP14、C7等顯著的上調，以及CLU、CFI、C3aR1表現量顯著下降。這些表現量的變化可歸納造成更嚴重的脈絡膜新生血管、發炎反應以及補體過度的活化，這些結果皆指向飛灰中的PAHs會引發或促進老年性黃斑部病變的病情發展。

Age-related macular degeneration (AMD) is one of common causes of severe loss of vision in elder population. Oxidative stress in retinal pigment epithelium (RPE) plays the principal role in AMD. Considering the bio-accumulative and lipid-solubility, we focus one crucial oxidative stress trigger on environmental pollutants: polycyclic aromatic hydrocarbons (PAHs) in respirable particulate matter, PM2.5-1 (diameter 2.5-1μm), from municipal solid waste (MSW) incinerator. MSW fly ash sample contained 1.795% respirable PM (diameter<10μm), including 0.128% of PM2.5-1, which was classified by Dekati® Low Pressure Impactor. Then, PAHs in PM2.5-1 quantified by GC-MS were 11.3 ppm. To identify if PAHs in PM2.5-1 is a risky factor of AMD, EC50, ROS, transepithelial electrical resistance, immunofluorescence staining and variation of genomic expression were measured. PAHs and PM2.5-1 both induced ROS progressed the oxidative stress in ARPE-19 cells. Moreover, they both interfered the integrity of the tight junction protein, ZO-1, at REP monolayer. On the other hand, our results demonstrated the expression levels of CCL2, CRP, CXCL1, CXCL12, ITGB2, MMP14, and C7 in ARPE-19 cells were up-regulated whereas the levels of CLU, CFI, and C3aR1 were down-regulated after PAHs exposed. These variation of genomic expression was regarded as an indicator of severe CNV, inflammation and uncontrolled complement activity. In conclusion, all findings suggested an association between PAHs exposure and development of AMD.

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