Knepper Paul A, Samples John R, Yue Beatrice Yjt
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor, Chicago, IL 60612, USA ; Department of Ophthalmology, Northwestern University Medical School, 150 East Huron, Suite 1000, Chicago, IL 60611, USA.
Casey Eye Institute, Oregon Health and Sciences University, Portland, OR, USA ; Rocky Vista University, 11960 Lioness Way, Parker, CO 80134, USA.
Expert Rev Ophthalmol. 2010 Dec;5(6):731-742. doi: 10.1586/EOP.10.73.
Primary open-angle glaucoma (POAG) is a primary neuronal disease of the optic nerve without a definable cause, and is often associated with increased intraocular pressure. Worldwide, POAG is the second leading cause of blindness; there are 45 million people today with POAG and bilateral blindness is present in 4.5 million of these. In order to elucidate the possible etiologic factors in POAG, we have cataloged all known biomarkers in the aqueous humor, trabecular meshwork, optic nerve and blood into four categories, namely extracellular matrix (ECM), cell signaling molecules, aging/stress and immunity-related changes. We present a theoretical model to show possible signaling pathways of the ECM, cell signaling and innate immune response through activation of Toll-like receptor 4. Our article suggests that ECM and innate immune biomarkers are the lead candidates for developing the 'POAG biomarker signature'. We suggest that current research is critical to pinpoint the causes of the disease so that new treatment modalities can become available for better regulation of the intraocular pressure and neuroprotection of the optic nerve.
原发性开角型青光眼(POAG)是一种病因不明的原发性视神经疾病,常与眼压升高有关。在全球范围内,POAG是导致失明的第二大主要原因;目前有4500万人患有POAG,其中450万人双眼失明。为了阐明POAG可能的病因,我们已将房水、小梁网、视神经和血液中所有已知的生物标志物归类为四类,即细胞外基质(ECM)、细胞信号分子、衰老/应激和免疫相关变化。我们提出了一个理论模型,以展示通过激活Toll样受体4,ECM、细胞信号和先天免疫反应可能的信号通路。我们的文章表明,ECM和先天免疫生物标志物是开发“POAG生物标志物特征”的主要候选物。我们认为,当前的研究对于查明该疾病的病因至关重要,以便能够采用新的治疗方法更好地调节眼压并对视神经进行神经保护。