Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China; Key Laboratory of Myopia, NHFPC (Fudan University), and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, 200031, China.
Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, iChEM, Fudan University, Shanghai, 200433, China.
Exp Eye Res. 2021 Jan;202:108280. doi: 10.1016/j.exer.2020.108280. Epub 2020 Oct 15.
Nitric oxide (NO) donors are promising therapeutic candidates for treating intraocular hypertension (IOP) and glaucoma. This study aims to investigate the effect of prolonged use of NO donor sodium nitroprusside (SNP) on IOP. Since SNP has a short biological half-life, a nanoparticle drug delivery system (mesoporous silica nanoparticles) has been used to deliver SNP to the target tissues (trabecular meshwork and Schlemm's canal). We find that the sustained use of NO donor initially reduced IOP followed, surprisingly, by IOP elevation, which could not recover by drug withdraw but could be reversed by the antioxidant MnTMPyP application. The IOP elevation and normalization coincide with increased and reduced protein nitration in the mouse conventional outflow tissue. These findings suggest that the prolonged use of NO donor SNP may be problematic as it can cause outflow tissue damage by protein nitration. MnTMPyP is protective of the nitrative damage which could be considered to be co-applied with NO donors.
一氧化氮（NO）供体是治疗眼内高压（IOP）和青光眼的有前途的治疗候选物。本研究旨在研究NO 供体硝普钠（SNP）的长期使用对IOP 的影响。由于 SNP 的生物半衰期短，因此使用纳米颗粒药物递送系统（介孔硅纳米颗粒）将 SNP 递送到靶组织（小梁网和施莱姆氏管）。我们发现，NO 供体的持续使用最初降低了 IOP，随后出人意料地升高了 IOP，药物撤出后无法恢复，但抗氧化剂 MnTMPyP 的应用可使其逆转。IOP 升高和正常化与小鼠常规流出组织中蛋白质硝化的增加和减少相吻合。这些发现表明，NO 供体 SNP 的长期使用可能会有问题，因为它可能会通过蛋白质硝化导致流出组织损伤。MnTMPyP 对硝化损伤具有保护作用，可与 NO 供体共同应用。
