Department of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.
Department of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.
Redox Biol. 2022 Aug;54:102375. doi: 10.1016/j.redox.2022.102375. Epub 2022 Jun 16.
Ariboflavinosis is a pathological condition occurring as a result of riboflavin deficiency. This condition is treatable if detected early enough, but it lacks timely diagnosis. Critical symptoms of ariboflavinosis include neurological and visual manifestations, yet the effects of flavin deficiency on the retina are not well investigated. Here, using a diet induced mouse model of riboflavin deficiency, we provide the first evidence of how retinal function and metabolism are closely intertwined with riboflavin homeostasis. We find that diet induced riboflavin deficiency causes severe decreases in retinal function accompanied by structural changes in the neural retina and retinal pigment epithelium (RPE). This is preceded by increased signs of cellular oxidative stress and metabolic disorder, in particular dysregulation in lipid metabolism, which is essential for both photoreceptors and the RPE. Though many of these deleterious phenotypes can be ameliorated by riboflavin supplementation, our data suggests that some patients may continue to suffer from multiple pathologies at later ages. These studies provide an essential cellular and mechanistic foundation linking defects in cellular flavin levels with the manifestation of functional deficiencies in the visual system and paves the way for a more in-depth understanding of the cellular consequences of ariboflavinosis.
核黄素缺乏症是一种由于核黄素缺乏而引起的病理状态。如果及早发现，这种情况是可以治疗的，但缺乏及时的诊断。核黄素缺乏症的严重症状包括神经和视觉表现，但黄素缺乏对视网膜的影响尚未得到充分研究。在这里，我们使用饮食诱导的小鼠核黄素缺乏模型，首次提供了证据，证明视网膜功能和代谢与核黄素体内平衡密切相关。我们发现，饮食诱导的核黄素缺乏会导致严重的视网膜功能下降，同时伴有神经视网膜和视网膜色素上皮（RPE）的结构变化。这之前是细胞氧化应激和代谢紊乱迹象的增加，特别是脂质代谢的失调，这对光感受器和 RPE 都是必不可少的。尽管许多这些有害表型可以通过核黄素补充来改善，但我们的数据表明，一些患者在以后的年龄可能会继续遭受多种病理。这些研究为细胞黄素水平缺陷与视觉系统功能缺陷的表现之间提供了一个重要的细胞和机制基础，并为更深入地了解核黄素缺乏症的细胞后果铺平了道路。
