以大鼠近視模型探討廣譜發光二極體光源對眼球生長及近視控制之效果

Abstract

近幾十年來近視盛行率上升已成為全球公共衛生問題。研究證實遺傳和環境因素均會影響近視的形成和惡化。近視的病理機轉涉及視覺刺激所引起的細胞內訊息傳遞和後續鞏膜組織重塑。目前以藥物和光學方法控制近視仍有其限制，故本研究希望尋找新的治療方式。已知戶外活動對於近視有保護效果，故這個研究使用新型發光二極體技術來模擬自然光之光譜分佈，以探究能有效控制近視的室內照明光源。 本研究以大鼠近視模型來探討廣譜發光二極體光源搭配亮暗週期對大鼠眼球生長及屈光度發育之影響。實驗以三週齡的Sprague-Dawley大鼠，右眼眼瞼注射TGF-β2 誘發形式剝奪性近視。分別以窄光譜白色LED光（narrow-spectrum white light emitting diodes, NSLED）和廣譜白色LED光（broad-spectrum white LED, BSLED）進行照光實驗21天。並由五種明暗循環（0小時/24小時、8小時/16小時、12小時/12小時、16小時/8小時、24小時/0小時）搭配兩種LED光源進行實驗。在第0天和21天記錄眼軸長度、屈光狀態和視網膜電生理檢測結果，最後再對視網膜進行免疫組織化學染色，探討光源調控眼球生長之訊息傳遞與分子機轉。 在沒有照光的情況下（0小時組），注射TGF-β2的眼睛有最大的眼軸增長。在5種亮暗循環中，窄光譜LED照明（NSLED）組別的眼軸長度增加比廣譜LED照明（BSLED）組更多。在BSLED照明的8小時光照週期下飼養的大鼠，其近視屈光度比NSLED組和對照組少。比較在第0天和照光21天後的電生理檢測結果，BSLED和NSLED的長時間照明組別（16小時和24小時組）呈現視桿細胞和雙極細胞的電生理訊號振幅減小。免疫組織化學染色分析顯示視網膜的TGF-β、MMP-2和TNF-α在BSLED組的表現量比NSLED組低。 我們的實驗結果顯示，相較於NSLED光源，以BSLED在每日8小時亮/16小時暗的照明週期下可以安全地減少眼軸長度增加和近視惡化。BSLED照明可能透過降低視網膜中的TGF-β、MMP-2和TNF-α表現，來調節鞏膜細胞外基質的重塑過程，進而減緩眼球生長。未來的研究仍需要進一步評估BSLED光源對人類眼球生長的影響，以提供預防近視的治療新選擇。

Background: The increasing prevalence of myopia has become a global public health issue in recent decades. Both genetic and environmental factors, including near work and insufficient natural light, contribute to myopia pathogenesis and progression. Myopia pathogenesis involves altered intra-cellular signaling pathways from visual stimuli and resultant scleral tissue remodeling. Despite currently available pharmacological and optical intervention targeting on the pathogenesis, our study is looking for different possible treatment. Indoor luminaires using new technology of light emitting diodes with spectral distributions resembling natural light may be a new avenue of research. Purpose: To investigate the impact of broad-spectrum light emitting diodes (LEDs) with different light/dark cycles on ocular growth and refractive error development in a rat model of myopia. Methods: A total of 80 3-week-old Sprague-Dawley rats received eyelid injection of TGF-β2 in the right eye for myopia induction. Animals were exposed to one of two light source for 21 days: broad-spectrum white LED (BSLED) light and narrow-spectrum white LED light (NSLED). Five patterns of light/dark cycle of isoluminant LED light (500 Lux) were applied to the subgroups respectively, including 0hr/24hr, 8hr/16hr, 12hr/12hr, 16hr/8hr and 24hr/0hr of light/dark cycles. Change in the axial length, refractive status and electroretinogram were recorded on day 0 and day 21. Histology study of retina with immunohistochemistry stains of related signaling molecules were conducted in these rats. Results: Largest axial length increase was observed in the TGF-β2 injected eyes without light exposure (0hr group). Axial length increased more in the NSLED-illuminated eyes than BSLED groups among 5 light/dark cycles.The rats raised under 8hr light cycle of BSLED illumination showed less myopic refraction than the NSLED group and the control group. Comparison between the ERG on day 0 and 21 revealed deceased amplitude of rod and bipolar cells with prolonged illumination (16hr and 24 hr group) of BSLED and NSLED. Immunohistochemical analysis of TGF-β, MMP-2 and TNF-α in outer retina exhibited lower expression in BSLED groups than NSLED groups. Conclusions: Our results suggested that compared to NSLED, BSLED can reduce axial length elongation and myopia progression with 8/16 light/dark cycle safely. BSLED light protected ocular growth potentially through decreased retinal levels of TGF-β, MMP-2 and TNF-α, which regulate scleral extracellular matrix remodeling. Further studies are necessary to evaluate the impact of BSLED light on human ocular growth to offer new option for myopia prevention.