Abstract:
Glaucoma is the leading cause of irreversible blindness globally. The most prevalent subtype, Primary Open Angle Glaucoma (POAG), is characterized by increased intraocular pressure (IOP), damage to the optic nerve head and irreversible visual loss. IOP increases aqueous humor (AqH) outflow is reduced through the trabecular meshwork (TM) and Schlemm\'s canal (SC). Increased outflow resistance is partly due to TM/SC dysregulation, including loss of normal trabecular meshwork cell (TMC) function, following increased levels of oxidative stress within TMC, dysregulated extracellular matrix (ECM) deposition and remodeling alongside alterations in TMC phenotype and apoptosis. Current widely available POAG treatments do not target the aberrant expression of ECM in the TM directly. As a result, most drug treatments can fail as the underlying pathological process continues unabated. Rho-kinase inhibitors have demonstrated the benefit of restoring TM/SC function, however there is a clear need to develop further treatment strategies that can target the underlying cellular processes which become dysregulated within the TMC during POAG pathogenesis. Vitamin D is suggested to be beneficial in alleviating the symptoms of fibrosis and inflammation in soft tissues. It has important functions in many major organ systems, including regulation of calcium, phosphate and parathyroid hormone. Evidence suggests that Vitamin D3 modulates ECM turnover through the conventional TGFβ-SMAD signaling, which is associated with the development of POAG. The link between Vitamin D3, inflammation and fibrosis within ocular tissues will be discussed and the potential roles of Vitamin D3 in the management of POAG patients will be explored within this review.
摘要:
青光眼是全球不可逆失明的主要原因。最普遍的亚型,原发性开角型青光眼(POAG),以眼内压(IOP)升高为特征,视神经头损伤和不可逆的视力丧失。眼压增加房水(AqH)通过小梁网(TM)和Schlemm管(SC)流出减少。流出阻力增加部分是由于TM/SC失调,包括正常小梁细胞(TMC)功能的丧失,随着TMC内氧化应激水平的增加,异常调节的细胞外基质(ECM)沉积和重塑以及TMC表型和凋亡的改变。当前广泛可用的POAG治疗不直接靶向TM中ECM的异常表达。因此,随着潜在的病理过程有增无减,大多数药物治疗可能会失败。Rho激酶抑制剂已经证明了恢复TM/SC功能的益处,然而,显然需要开发进一步的治疗策略,以靶向在POAG发病过程中TMC内失调的潜在细胞过程.维生素D有助于减轻软组织纤维化和炎症的症状。它在许多主要器官系统中具有重要功能,包括钙的调节,磷酸盐和甲状旁腺激素。有证据表明,维生素D3通过常规的TGFβ-SMAD信号调节ECM周转,这与POAG的发展有关。将讨论维生素D3,眼部组织内炎症和纤维化之间的联系,并在这篇综述中探讨维生素D3在POAG患者管理中的潜在作用。