Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, Republic of China.
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Republic of China.
Am J Physiol Endocrinol Metab. 2021 Jun 1;320(6):E1173-E1182. doi: 10.1152/ajpendo.00001.2021. Epub 2021 May 10.
Retinopathy is a leading cause of blindness, and there is currently no cure. Earlier identification of the progression of retinopathy could provide a better chance for intervention. Diet has profound effects on retinal function. A maternal high-fructose diet (HFD) triggers diseases in multiple organs. However, whether maternal HFD impairs retinal function in adult offspring is currently unknown. By using the rodent model of maternal HFD during pregnancy and lactation, our data indicated a reduced b-wave of electroretinography (ERG) in HFD female offspring at 3 mo of age compared with age-matched offspring of dams fed regular chow (ND). Immunofluorescence and Western blot analyses indicated that the distributions and expressions of synaptophysin, postsynaptic density protein 95 (PSD95), and phospho(p)-Ca/calmodulin-stimulated protein kinase IIα (CaMKIIα) were significantly suppressed in the HFD group. Furthermore, the ATP content and the mitochondrial respiratory protein, Mt CPX 4-2, were decreased. Moreover, the expressions of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and mitochondrial transcription factor A (TFAM) in the retina of the HFD group were downregulated. Treatment with coenzyme Q (Q10), a key mediator of the electron transport chain, effectively reversed these abovementioned dysfunctions. Together, these results suggested that maternal HFD impaired retinal function in adult female offspring. The mechanism underlying early-onset retinopathy may involve the reduction in the capacity of mitochondrial energy production and the suppression of synaptic plasticity. Most importantly, mitochondria could be a feasible target to reprogram maternal HFD-damaged retinal function. In this study, we provide novel evidence that maternal high-fructose diet during gestation and lactation could induce early-onset retinopathy in adult female offspring. Of note, the insufficient energy content, downregulated mitochondrial respiratory complex 4-2, and impaired mitochondrial biogenesis might contribute to the decrease of synaptic plasticity resulting in retinal function suppression. Oral application with coenzyme Q for 4 wk could at least partially reverse the aforementioned molecular events and retinal function.
视网膜病变是失明的主要原因，但目前尚无治愈方法。更早地识别视网膜病变的进展可能为干预提供更好的机会。饮食对视网膜功能有深远的影响。母体高果糖饮食（HFD）会引发多种器官疾病。然而，母体 HFD 是否会损害成年后代的视网膜功能目前尚不清楚。通过使用孕期和哺乳期母体 HFD 的啮齿动物模型，我们的数据表明，与年龄匹配的正常饮食（ND）喂养的母鼠所生后代相比，HFD 雌性后代在 3 月龄时的视网膜电图（ERG）b 波幅度降低。免疫荧光和 Western blot 分析表明，突触小体蛋白、突触后密度蛋白 95（PSD95）和磷酸化（p）-钙/钙调蛋白依赖性蛋白激酶 IIα（CaMKIIα）的分布和表达在 HFD 组中明显受到抑制。此外，ATP 含量和线粒体呼吸蛋白 Mt CPX 4-2 减少。此外，HFD 组视网膜中过氧化物酶体增殖物激活受体γ共激活因子 1-α（PGC-1α）和线粒体转录因子 A（TFAM）的表达下调。辅酶 Q（Q10）作为电子传递链的关键介质的治疗有效逆转了上述功能障碍。总之，这些结果表明母体 HFD 损害了成年雌性后代的视网膜功能。早发性视网膜病变的机制可能涉及线粒体能量产生能力的降低和突触可塑性的抑制。最重要的是，线粒体可能是一种可行的靶点，可以重新编程母体 HFD 损伤的视网膜功能。在这项研究中，我们提供了新的证据，表明孕期和哺乳期母体高果糖饮食可导致成年雌性后代早发性视网膜病变。值得注意的是，能量含量不足、下调的线粒体呼吸复合物 4-2 和受损的线粒体生物发生可能导致突触可塑性降低，从而抑制视网膜功能。口服辅酶 Q 4 周至少可以部分逆转上述分子事件和视网膜功能。
