Piano Ilaria, Corsi Francesca, Polini Beatrice, Gargini Claudia
Department of Pharmacy, University of Pisa, Pisa, Italy.
Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
Front Neurosci. 2022 Apr 19;16:868750. doi: 10.3389/fnins.2022.868750. eCollection 2022.
Rhodopsin (RHO) mutations are responsible for 25-40% of the dominant cases of retinitis pigmentosa (RP) with different severity and progression rates. The Tvrm4 mice, heterozygous for an I307N dominant mutation of RHO, display a normal retinal phenotype when raised in ambient light conditions, but undergo photoreceptor degeneration when briefly exposed to strong white light. Here, The Tvrm4 mice is pre-treated with naringenin 100 mg/kg/die, quercetin 100 mg/kg/die, naringenin 50 + quercercetin 100 mg/kg/die or vehicle dimethyl sulfoxide (DMSO 0.025%) in the drinking water for 35 days. On the 30th day, retinal degeneration was induced by exposure for 1 min to the white light of 12,000 lux intensity, and the treatment was repeated for another 5 days. At the end of the protocol retinal functionality was tested by recording an electroretinogram (ERG). The retinal tissue was collected and was used for further analyses, including immunohistochemically, biochemical, and molecular biology assays. The data obtained show that treatment with nutraceutical molecules is effective in counteracting retinal degeneration by preserving the functionality of photoreceptors and increasing the antioxidant and anti-apoptotic pathways of retinal cells. The present data confirm that nutraceutical molecules are effective in slowing photoreceptor degeneration in a mutation-independent way by modulating the antioxidant response of the retina at the gene expression level.
视紫红质（RHO）突变是导致25%-40%显性色素性视网膜炎（RP）病例的原因，这些病例具有不同的严重程度和进展速度。Tvrm4小鼠为RHO基因I307N显性突变的杂合子，在环境光条件下饲养时表现出正常的视网膜表型，但在短暂暴露于强光下时会发生光感受器退化。在此，将Tvrm4小鼠用100 mg/kg/天的柚皮素、100 mg/kg/天的槲皮素、50 mg/kg/天的柚皮素 + 100 mg/kg/天的槲皮素或载体二甲基亚砜（0.025% DMSO）在饮用水中预处理35天。在第30天，通过暴露于强度为12000勒克斯的白光1分钟来诱导视网膜退化，并将该处理再重复5天。在实验方案结束时，通过记录视网膜电图（ERG）来测试视网膜功能。收集视网膜组织并用于进一步分析，包括免疫组织化学、生化和分子生物学检测。获得的数据表明，用营养分子进行治疗可通过保留光感受器的功能并增加视网膜细胞的抗氧化和抗凋亡途径来有效对抗视网膜退化。目前的数据证实，营养分子通过在基因表达水平调节视网膜的抗氧化反应，以与突变无关的方式有效减缓光感受器退化。
