Sharif Najam A
Department of Global Alliances & External Research, Global Ophthalmology Research & Development, Santen Incorporated, Emeryville, CA; Department of Pharmaceutical Sciences, Texas Southern University, Houston, TX; Department of Pharmacology and Neuroscience, University of North Texas Health Sciences Center, Fort Worth, TX; Department of Pharmacy Sciences, Creighton University, Omaha, Nebraska USA; Department of Surgery & Cancer, Imperial College of Science and Technology, St. Mary's Campus, London, UK.
Neural Regen Res. 2018 Jul;13(7):1145-1150. doi: 10.4103/1673-5374.235017.
Peripheral vision loss followed by "tunnel vision" and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma (POAG) and normotensive glaucoma (NTG). These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells (RGCs) accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve. Since patients suffering from this glaucomatous optic neuropathy (GON) first notice visual impairment when they have lost > 40% of their RGCs, early diagnosis is the key to retard the progression of glaucoma. Elevated intraocular pressure (IOP), low cerebrospinal and/or low intracranial fluid pressure, advancing age, and ethnicity are major risk factors associated with POAG. However, retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic, inflammatory, oxidative and mechanical insults also contribute to vision loss in POAG/GON. Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs, combination drug products, and surgical interventions. Two recently approved multi-pharmacophoric drugs (e.g., rho kinase inhibitor, Netarsudil; a drug conjugate, Latanoprostene Bunod) and novel aqueous humor drainage devices (iStent and CyPass) are also gaining acceptance for treating POAG/ NTG. Neuroprotective and regenerative agents, coupled with electroceutical, mechanical support systems, stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON. The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures, thereby providing a gain of function of the visual system for the glaucoma patients.
包括原发性开角型青光眼（POAG）和正常眼压性青光眼（NTG）在内的各种形式青光眼患者的最终命运是周边视力丧失，随后出现“管状视野”并最终导致不可逆的失明。这些复杂且异质性的疾病的特征是视网膜神经节细胞（RGCs）大量死亡，并伴有其与大脑的轴突连接回缩和切断，从而导致视神经损伤和变薄。由于患有这种青光眼性视神经病变（GON）的患者在RGCs损失超过40%时才首次注意到视力损害，因此早期诊断是延缓青光眼进展的关键。眼压升高、脑脊液和/或颅内压降低、年龄增长和种族是与POAG相关的主要危险因素。然而，视网膜血管异常以及RGCs和视神经头成分对神经毒性、炎症、氧化和机械损伤的高敏感性也导致了POAG/GON患者的视力丧失。目前POAG和NTG的治疗方式包括使用局部眼药、联合药物产品和手术干预来降低眼压。两种最近获批的多药效团药物（如Rho激酶抑制剂奈他地尔；药物偶联物比马前列素丁二醇酯）和新型房水引流装置（iStent和CyPass）也越来越被接受用于治疗POAG/NTG。神经保护和再生剂，再加上电治疗、机械支持系统、干细胞移植和基因治疗，是即将出现的有助于对抗GON的治疗方法。后几种技术和方法希望使RGCs恢复活力并修复视神经结构，从而为青光眼患者提供视觉系统功能的恢复。
