Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Advanced Pediatrics Centre, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
PLoS One. 2021 Jun 1;16(6):e0248523. doi: 10.1371/journal.pone.0248523. eCollection 2021.
Degeneration of macular photoreceptors is a prominent characteristic of age-related macular degeneration (AMD) which leads to devastating and irreversible vision loss in the elderly population. In this exploratory study, the contribution of environmental factors on the progression of AMD pathology by probing the expression of candidate proteins was analyzed. Four hundred and sixty four participants were recruited in the study comprising of AMD (n = 277) and controls (n = 187). Genetics related data was analyzed to demonstrate the activities of daily living (ADL) by using regression analysis and statistical modeling, including contrast estimate, multinomial regression analysis in AMD progression. Regression analysis revealed contribution of smoking, alcohol, and sleeping hours on AMD by altered expression of IER-3, HTRA1, B3GALTL, LIPC and TIMP3 as compared to normal levels. Contrast estimate supports the gender polarization phenomenon in AMD by significant decreased expression of SLC16A8 and LIPC in control population which was found to be unaltered in AMD patients. The smoking, food habits and duration of night sleeping hours also contributed in AMD progression as evident from multinomial regression analysis. Predicted model (prediction estimate = 86.7%) also indicated the crucial role of night sleeping hours along with the decreased expression of TIMP-3, IER3 and SLC16A8. Results revealed an unambiguous role of environmental factors in AMD progression mediated by various regulatory proteins which might result in intermittent AMD phenotypes and possibly influence the outcome of anti-VEGF treatment.
黄斑感光细胞的变性是年龄相关性黄斑变性(AMD)的一个突出特征,它导致老年人群视力严重且不可逆转的丧失。在这项探索性研究中,通过探测候选蛋白的表达来分析环境因素对 AMD 病理进展的贡献。这项研究共招募了 464 名参与者,包括 AMD 患者(n = 277)和对照组(n = 187)。分析遗传相关数据以通过回归分析和统计建模来证明日常生活活动(ADL)的情况,包括对比估计、AMD 进展中的多项回归分析。回归分析显示,吸烟、饮酒和睡眠时间的改变会影响 IER-3、HTRA1、B3GALTL、LIPC 和 TIMP3 的表达,从而导致 AMD 的发生。对比估计支持 AMD 中的性别两极化现象,因为在对照组中 SLC16A8 和 LIPC 的表达显著降低,而在 AMD 患者中则没有改变。吸烟、饮食习惯和夜间睡眠时间也会导致 AMD 的进展,这可以从多项回归分析中得到证实。预测模型(预测估计=86.7%)也表明夜间睡眠时间以及 TIMP-3、IER3 和 SLC16A8 的表达降低在 AMD 进展中起着至关重要的作用。结果表明,环境因素通过各种调节蛋白在 AMD 进展中起着明确的作用,这可能导致间歇性 AMD 表型,并可能影响抗 VEGF 治疗的结果。