Lee Soomin, Park Choul Yong
Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South Korea.
Ann Transl Med. 2023 Aug 30;11(10):352. doi: 10.21037/atm-22-5634. Epub 2023 Jun 6.
Based on basic knowledge and prior research on nitric oxide (NO), the potential of NO for treating eye diseases is reviewed, and the possibility of NO-based eye drops in clinical practice and the future potential of NO in ophthalmology are discussed.
A PubMed search was performed for English-language original reports and reviews using the following key words: nitric oxide, eye, ocular, and drug.
NO is synthesized in the human body by NO synthase (NOS) from L-arginine or through enzyme-dependent reduction of dietary nitrate. Three types of NOS (eNOS, nNOS, and iNOS) are abundantly expressed in the eye under normal physiologic or pathologic conditions. The biological effect of NO in the eye is dose dependent. Low intraocular NO concentrations, produced by eNOS or nNOS, have various cellular effects, including vasodilation, intraocular pressure (IOP) regulation, and neuroprotection. iNOS induced under pathologic ocular conditions produces high NO concentrations in the local environment and mediates tissue inflammation, ocular cell apoptosis, and neurodegeneration. In particular, increased iNOS has been reported in glaucoma and retinal ischemic or degenerative diseases. NO plays a vital role in ocular injury. NO can facilitate ocular surface wound healing while eradicating pathogens such as bacteria and Acanthamoeba in chemical burns or infectious keratitis. Furthermore, NO has antifibrotic activity via the cyclic guanosine monophosphate (cGMP) signaling pathway. NO causes smooth muscle relaxation, which can be used to inhibit myopia progression in children. NO can be a stem cell modulator and may help in treating ocular stem cell disorders.
Because of its diverse biologic effects, NO can be a key player in regulating ocular inflammation in various ocular diseases, aiding ocular surface wound healing, controlling IOP in glaucoma, alleviating retinal disease, and suppressing myopia progression. Although there remain limitations to the effective use of highly unstable state, gaseous NO, the role of NO in the field of ophthalmology can be greatly expanded through the development of novel NO donors and effective delivery platforms.
基于一氧化氮（NO）的基础知识和先前研究，综述NO治疗眼部疾病的潜力，并讨论基于NO的眼药水在临床实践中的可能性以及NO在眼科领域的未来潜力。
使用以下关键词在PubMed上搜索英文原始报告和综述：一氧化氮、眼睛、眼部、药物。
NO在人体内由一氧化氮合酶（NOS）从L-精氨酸合成，或通过饮食硝酸盐的酶依赖性还原产生。在正常生理或病理条件下，三种类型的NOS（内皮型NOS、神经元型NOS和诱导型NOS）在眼中大量表达。NO在眼中的生物学效应是剂量依赖性的。由内皮型NOS或神经元型NOS产生的低眼内NO浓度具有多种细胞效应，包括血管舒张、眼压（IOP）调节和神经保护。在病理性眼部条件下诱导产生的诱导型NOS在局部环境中产生高浓度的NO，并介导组织炎症、眼细胞凋亡和神经退行性变。特别是，在青光眼以及视网膜缺血或退行性疾病中已报道诱导型NOS增加。NO在眼损伤中起重要作用。NO可促进眼表伤口愈合，同时在化学烧伤或感染性角膜炎中根除细菌和棘阿米巴等病原体。此外，NO通过环磷酸鸟苷（cGMP）信号通路具有抗纤维化活性。NO引起平滑肌松弛，可用于抑制儿童近视进展。NO可以是一种干细胞调节剂，可能有助于治疗眼干细胞疾病。
由于其多样的生物学效应，NO可能是调节各种眼部疾病中的眼部炎症、辅助眼表伤口愈合、控制青光眼眼压、缓解视网膜疾病以及抑制近视进展的关键因素。尽管在有效使用高度不稳定状态的气态NO方面仍存在局限性，但通过开发新型NO供体和有效的递送平台，NO在眼科领域的作用可以得到极大扩展。
