長期高果糖高脂飲食促進小鼠視網膜對藍光損傷之敏感性
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2023
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藍光 (blue light, BL)因波長短能量高，易引發眼球之活性氧物質 (reactive oxygen substrate, ROS)生成，造成視網膜組織光化學性損傷 (photochemical damage)。我們過去的研究證實，若小鼠暴露趨近日常環境的藍光強度八週後，會造成感光細胞核數與outer nuclear layer (ONL)厚度下降等損傷。有鑑於飲食因子亦可能不利於眼球健康，且飲食型態對於光化學性損傷之交互作用目前仍較少文獻可循，因此本研究擬探討高果糖高脂 (high-fructose and high-fat, HFHF)飲食對於BL誘發視網膜損傷之影響。雄性ICR小鼠，將其隨機分成三組：(1) 控制組 (Control group, Ctrl)；(2) 藍光照射組 (BL group)，與 (3) 藍光照射合併高果糖高脂飲食組 (BL + HFHF group)。試驗動物於給予HFHF diet四十週後另接受為期八週每日六小時之低強度藍光 (37.7 lux, 0.8 μW)照射。結果顯示HFHF diet可造成小鼠胰島素阻抗及血清total triglyceride (TG)、total cholesterol (TC)、malonaldehyde (MDA)及螢光性advanced glycated end products (AGEs)上升的現象。Hematoxylin& eosin (H&E) staining分析證實，長期攝取HFHF diet會加劇BL對於視網膜組織之病理型態改變，其感光細胞核數與outer nuclear layer (ONL)及inner segment/outer segment (IS/OS)厚度皆顯著低於BL組 (p ＜ 0.05)。Immunofluorescence staining (IF)顯示，與控制組比較，BL照射可顯著造成視網膜組織rhodopsin表現下降與glial fibrillary acidic protein (GFAP)、8-hydroxy-2-deoxyguanosine (8-OHdG)表現上升並同時增加nuclear factor erythroid 2-related factor 2 (Nrf2)與super oxide dismutase1 (SOD1)抗氧化相關蛋白及凋亡指標terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) (p ＜ 0.05)，而HFHF diet可顯著加劇上述BL之負面作用並顯著提升抗氧化蛋白Nrf2、SOD1與catalase之表現量，並促進發炎激素interleukin-1β (IL-1β)及tumor necrosis factor-α (TNF-α)於視網膜內表現量，並造成血視網膜屏障滲漏 (blood retinal barrier leakage) (p ＜ 0.05)。同時，給予HFHF diet之動物視網膜內有高度糖化終產物 (advanced glycated end products, AGE)指標物如Nε-(1-carboxyethyl)lysine (CEL)與Nδ-(5-Methyl-4-imidazolon-2-yl)-L-ornithine (MG-H1)累積，其活化receptor for AGE (RAGE)並促進發炎小體 (inflammasome)之形成，以及視網膜細胞凋亡蛋白caspase-3及晚期凋亡指標TUNEL表現量增加 (p ＜ 0.05)。綜合上述，本研究證實，HFHF diet可加劇藍光造成之視網膜損傷，不健康的飲食型態可能為不利於眼球健康的負面因子，有待進一步的臨床研究探討。
Blue light is a short wavelength and high energy spectrum, making it easily reach the retina, which increases the reactive oxygen substrate (ROS) and causes photochemical damage to the retina. Our study discovered that exposure to low intensity blue light for 8 weeks induces retina damage in ICR mice, including a significant decrease the thickness of the outer nuclear layer (ONL) and the number of photoreceptor nuclei. Previous studies have shown that a Western-style diet, characterized by high-fructose and high-fat intake, poses an unhealthy risk for the retina. It increases oxidative stress, inflammatory responses, and the formation of advanced glycated end products (AGEs) in the retina. Therefore, the aim of this study was to investigate the impact of long-term consumption of a high-fructose and high-fat (HFHF) diet on blue light-induced retina damage in mice. Male ICR mice were randomly divided into three groups: (1) control group, Ctrl; (2) blue light group, BL; and (3) blue light exposure with HFHF diet, BL + HFHF. After 40 weeks of HFHF diet feeding, the mice were exposed to low intensity blue light for 8 weeks. During the intervention period, the HFHF diet significantlyincreased insulin resistance in the mice and elevated levels of total triglycerides (TG), total cholesterol (TC), malondialdehyde (MDA), and fluorescent AGEs in the serum. In the BL + HFHF group, hematoxylin& eosin (H & E) staining of the retina showed a significant decrease in the number of nuclei in photoreceptor cells, as well as in the thickness of the outer nuclear layer (ONL), inner nuclear layer (INL), and inner segment/outer segment (IS/OS) compared to the BL group. Furthermore, compared to the Ctrl group, the BL group exhibited the declined expression of the rhodopsin and increased expression of the glial fibrillary acidic protein (GFAP), 8-hydroxy-2-deoxyguanosine (8-OHdG), nuclear factorerythroid 2-related factor 2 (Nrf2), super oxide dismutase1 (SOD1), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the immunofluorescence (IF) staining of the retina (p< 0.05). Meanwhile, the BL + HFHF group showed higher expression of the Nrf2、SOD1, and catalase. Moreover, accumulated the advanced glycation end products (AGEs) significantly in the retinal tissues, such as Nε-(1-carboxyethyl)lysine (CEL) and Nδ-(5-Methyl-4-imidazolon-2-yl)-L-ornithine (MG-H1), along with activation of the receptor for AGE (RAGE) and phorsphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (phosphor-NFκB p65) could enhance th activaetion of inflammasome, but also upregulated the expression of the apoptosis relative protein and marker caspase-3 and TUNEL (p< 0.05). This study revealed that the HFHF diet exacerbates blue light-induced retinal damage, suggesting that an unhealthy dietary pattern may be a negative factor for ocular health, warranting further clinical investigation.
Blue light is a short wavelength and high energy spectrum, making it easily reach the retina, which increases the reactive oxygen substrate (ROS) and causes photochemical damage to the retina. Our study discovered that exposure to low intensity blue light for 8 weeks induces retina damage in ICR mice, including a significant decrease the thickness of the outer nuclear layer (ONL) and the number of photoreceptor nuclei. Previous studies have shown that a Western-style diet, characterized by high-fructose and high-fat intake, poses an unhealthy risk for the retina. It increases oxidative stress, inflammatory responses, and the formation of advanced glycated end products (AGEs) in the retina. Therefore, the aim of this study was to investigate the impact of long-term consumption of a high-fructose and high-fat (HFHF) diet on blue light-induced retina damage in mice. Male ICR mice were randomly divided into three groups: (1) control group, Ctrl; (2) blue light group, BL; and (3) blue light exposure with HFHF diet, BL + HFHF. After 40 weeks of HFHF diet feeding, the mice were exposed to low intensity blue light for 8 weeks. During the intervention period, the HFHF diet significantlyincreased insulin resistance in the mice and elevated levels of total triglycerides (TG), total cholesterol (TC), malondialdehyde (MDA), and fluorescent AGEs in the serum. In the BL + HFHF group, hematoxylin& eosin (H & E) staining of the retina showed a significant decrease in the number of nuclei in photoreceptor cells, as well as in the thickness of the outer nuclear layer (ONL), inner nuclear layer (INL), and inner segment/outer segment (IS/OS) compared to the BL group. Furthermore, compared to the Ctrl group, the BL group exhibited the declined expression of the rhodopsin and increased expression of the glial fibrillary acidic protein (GFAP), 8-hydroxy-2-deoxyguanosine (8-OHdG), nuclear factorerythroid 2-related factor 2 (Nrf2), super oxide dismutase1 (SOD1), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the immunofluorescence (IF) staining of the retina (p< 0.05). Meanwhile, the BL + HFHF group showed higher expression of the Nrf2、SOD1, and catalase. Moreover, accumulated the advanced glycation end products (AGEs) significantly in the retinal tissues, such as Nε-(1-carboxyethyl)lysine (CEL) and Nδ-(5-Methyl-4-imidazolon-2-yl)-L-ornithine (MG-H1), along with activation of the receptor for AGE (RAGE) and phorsphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (phosphor-NFκB p65) could enhance th activaetion of inflammasome, but also upregulated the expression of the apoptosis relative protein and marker caspase-3 and TUNEL (p< 0.05). This study revealed that the HFHF diet exacerbates blue light-induced retinal damage, suggesting that an unhealthy dietary pattern may be a negative factor for ocular health, warranting further clinical investigation.
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藍光, 長期高果糖高脂飲食, 高度糖化終產物, 氧化壓力, 發炎反應, 視網膜, blue light, long-term high-fructose and high-fat diet, AGEs, oxidative stress, inflammatory responses, retina