Nitric oxide: an old drug but with new horizons in ophthalmology-a narrative review.

Background and Objective: 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. Methods: A PubMed search was performed for English-language original reports and reviews using the following key words: nitric oxide, eye, ocular, and drug. Key Content and Findings: 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. Conclusions: 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.