The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on major blinding diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing 400016, People's Republic of China.
Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, 404100, People's Republic of China.
J Control Release. 2024 Sep;373:293-305. doi: 10.1016/j.jconrel.2024.07.031. Epub 2024 Jul 18.
Myopia represents a widespread global public health concern influenced by a combination of environmental and genetic factors. The prevailing theory explaining myopia development revolves around scleral extracellular matrix (ECM) remodeling, characterized by diminished Type I collagen (Col-1) synthesis and increased degradation, resulting in scleral thinning and eye axis elongation. Existing studies underscore the pivotal role of scleral hypoxia in myopic scleral remodeling. This study investigates the peroxidase-like activity and catalytic performance of octahedral Palladium (Pd) nanocrystals, recognized as nanozymes with antioxidative properties. We explore their potential in reducing oxidative stress and alleviating hypoxia in human scleral fibroblasts (HSF) and examine the associated molecular mechanisms. Our results demonstrate the significant peroxidase-like activity of Pd nanocrystals. Furthermore, we observe a substantial reduction in oxidative stress in HSF under hypoxia, mitigating cellular damage. These effects are linked to alterations in Nrf-2/Ho-1 expression, a pathway associated with hypoxic stress. Importantly, our findings indicate that Pd nanocrystals contribute to attenuated scleral matrix remodeling in myopic guinea pigs, effectively slowing myopia progression. This supports the hypothesis that Pd nanocrystals regulate myopia development by controlling oxidative stress associated with hypoxia. Based on these results, we propose that Pd nanocrystals represent a novel and potential treatment avenue for myopia through the modulation of scleral matrix remodeling. This study introduces innovative ideas and directions for the treatment and prevention of myopia.
近视是一个广泛存在的全球性公共健康问题,受到环境和遗传因素的共同影响。目前解释近视发展的主流理论围绕着巩膜细胞外基质(ECM)重塑展开,其特征是 I 型胶原蛋白(Col-1)合成减少和降解增加,导致巩膜变薄和眼轴延长。现有研究强调了巩膜缺氧在近视性巩膜重塑中的关键作用。本研究调查了八面体钯(Pd)纳米晶体的过氧化物酶样活性和催化性能,这些纳米晶体被认为是具有抗氧化特性的纳米酶。我们探讨了它们在减轻人巩膜成纤维细胞(HSF)氧化应激和缺氧中的潜在作用,并研究了相关的分子机制。我们的结果表明 Pd 纳米晶体具有显著的过氧化物酶样活性。此外,我们观察到在缺氧下 HSF 中的氧化应激显著减少,减轻了细胞损伤。这些效应与 Nrf-2/Ho-1 表达的改变有关,这是与缺氧应激相关的途径。重要的是,我们的发现表明 Pd 纳米晶体有助于减缓近视豚鼠的巩膜基质重塑,有效减缓近视进展。这支持了 Pd 纳米晶体通过控制与缺氧相关的氧化应激来调节近视发展的假说。基于这些结果,我们提出 Pd 纳米晶体通过调节巩膜基质重塑为近视的治疗提供了一种新的潜在途径。本研究为近视的治疗和预防提供了创新的思路和方向。