乙醯胺苯酚誘導肝損傷加重LED誘發視網膜病變之嚴重性

中醫典籍《黃帝內經》提到：「肝開竅於目」，是傳統中醫所稱「清肝明目」的理論基礎，然而欠缺充足的實驗證據。已知感光細胞位於視網膜內，需維生素A維持其光轉化生理功能。一般健康人體內約70~80%維生素A 儲存於肝臟的星狀細胞(hepatic stellate cell; HSC)，然而當肝臟受損、星狀細胞被活化，其儲存的維生素A便會流失。為探討肝臟星狀細胞活化，是否影響維生素A所參與的視網膜感光細胞功能 ，進一步驗證肝臟與眼睛間是否因維生素A而有所聯繫，本研究藉動物實驗，以乙醯胺苯酚(acetaminophen, APAP)誘導C57BL/6小鼠使其肝損傷、並以LED燈造成視網膜受損的雙重傷害模式，透過組織病理切片、體內維生素A濃度、視覺功能性評估，觀察肝臟及眼睛間相互影響之情形。 實驗結果發現，以乙醯胺苯酚所誘導肝損傷合併LED燈傷害之組別，其肝臟及視網膜所受到的傷害是所有組別中最嚴重的，而根據各項文獻及維生素A定量分析結果，證實視網膜及血液中維生素A濃度的變化會影響肝臟及視網膜所受的傷害嚴重程度。在LED光傷害的組別中，除了視覺功能異常、感光細胞及視網膜色素上皮細胞形態發生改變外，肝臟組織切片中出現小範圍細胞浸潤及部分肝臟星狀細胞活化；而在乙醯胺苯酚所誘導肝損傷的組別中，則有大範圍細胞浸潤、大量肝臟星狀細胞活化，伴隨視網膜柱狀細胞的rhodopsin凝集並聚縮形成細絲狀、視網膜色素上皮細胞中有lipofuscin的累積。維生素A定量分析結果顯示LED光傷害組的血清視網醇濃度下降、乙醯胺苯酚誘導肝損傷組的血清及視網膜中視網醇濃度下降之結果，推論肝損傷所造成的體內維生素A濃度變化會影響視網膜損傷程度，及LED燈所造成視覺循環對維生素A的需求增加，會逆向影響肝臟星狀細胞的穩定性，而引起肝臟受損。本項研究結果支持肝臟及視網膜會透過維生素A濃度的變化而相互影響。

Traditional Chinese medicine proclaims a relationship between liver function and eyesight, but in lack of experimental evidence. The photoreceptors locate within the retina, where vitamin A is essential for phototransduction. Around 70 -80% of vitamin A (retinoids) are reserved in the hepatic stellae cells (HSCs). When HSCs become activated upon liver injuries, their retinoids storage will be gradually depleted. This study investigated whether the role of vitamin A in visual cycle would be affected by the status of HSCs, or reversely, the condition of retinal physiology may affect liver function. A dual injuries animal model with hepatic injuries induced by over doses of acetaminophen and with concomitant retinopathy caused by excessive LED exposure was produced. The hepatic and retinal status was then compared among those with double injuries, single injury, and controls. The pathology of liver and retina was analyzed through tissue sections. Visual functions were assessed by pupil reflex assay and vitamin A concentrations were determined to elucidate the interaction between liver and retina. The results showed that, the dual liver and retina injuries caused by acetaminophen and LED lead to the most serious damages among all study correlated with the severity liver and retina damages. In the LED light injury group, beside visual function impairments, the photoreceptors and retinal pigment epithelium cells were also affected, along with partial hepatic stellate cell activation. In the acetaminophen-induced liver injury group, many retinal cell infiltration and extensive hepatic stellate cell activation were found. Besides, rhodopsin was aggregated and condensed to become filamentous, along with lipofuscin accumulation in the retinal pigment epithelium. The data confirmed that altered vitamin A concentration due to hepatic injury would affect the severity of retinopathy. Conversely, increasing vitamin A demand in visual cycle may also affect HSCs, resulting in liver injury. These current results support that liver and retina may interact with each other through vitamin A.