Nonexudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. Currently, there are no available treatments for NE-AMD. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks. Several lines of evidence strongly support the involvement of oxidative stress in NE-AMD-induced retinal pigment epithelium (RPE) and outer retina damage. Melatonin is a proven and safe antioxidant. Our aim was analysing the effect of melatonin in the RPE/outer retina damage within experimental NE-AMD. The treatment with melatonin starting 48 h after SCGx, which had no effect on the ubiquitous choriocapillaris widening, protected visual functions and avoided Bruch´s membrane thickening, RPE melanin content, melanosome number loss, retinoid isomerohydrolase (RPE65)-immunoreactivity decrease, and RPE and hotoreceptor ultrastructural damage induced within experimental NE-AMD exclusively located at the central temporal (but not nasal) region. Melatonin also prevented the increase in outer retina/RPE oxidative stress markers and a decrease in mitochondrial mass at 6 weeks post-SCGx. Moreover, when the treatment with melatonin started at 4 weeks post-SCGx, it restored visual functions and reversed the decrease in RPE melanin content and RPE65-immunoreactivity. These findings suggest that melatonin could become a promising safe therapeutic strategy for NE-AMD.

中文翻译：

---

褪黑素可保护视网膜免受小鼠实验性非渗出性年龄相关性黄斑变性的影响。

与年龄无关的黄斑变性（NE-AMD）代表了老年人失明的主要原因。目前，尚无NE-AMD的治疗方法。我们已经开发了由C57BL / 6J小鼠上颈神经节切除术（SCGx）诱导的NE-AMD模型，该模型再现了疾病的特征。有几条证据强烈支持氧化应激参与NE-AMD诱导的视网膜色素上皮细胞（RPE）和视网膜外部损伤。褪黑激素是一种经过验证的安全抗氧化剂。我们的目的是分析褪黑激素在实验性NE-AMD中对RPE /视网膜外层损伤的作用。在SCGx后48小时开始用褪黑素进行治疗，这对无处不在的脉络膜毛细血管扩张没有影响，保护了视觉功能，避免了Bruch的膜增厚，RPE黑色素含量，黑素体数量减少，类视黄醇异构酶（RPE65）的免疫反应性降低，并且在实验性NE-AMD内（仅位于中央颞部（而非鼻部）区域）诱发RPE和热感受器超微结构损伤。在SCGx术后6周，褪黑激素还阻止了外部视网膜/ RPE氧化应激标志物的增加和线粒体质量的减少。此外，当褪黑激素治疗在SCGx术后4周开始时，它恢复了视觉功能，并扭转了RPE黑色素含量和RPE65免疫反应性的下降。这些发现表明褪黑激素可能成为NE-AMD的一种有前途的安全治疗策略。在SCGx术后6周，褪黑激素还阻止了外部视网膜/ RPE氧化应激标志物的增加和线粒体质量的减少。此外，当褪黑激素治疗在SCGx术后4周开始时，它恢复了视觉功能，并扭转了RPE黑色素含量和RPE65免疫反应性的下降。这些发现表明褪黑激素可能成为NE-AMD的一种有前途的安全治疗策略。在SCGx术后6周，褪黑激素还阻止了外部视网膜/ RPE氧化应激标志物的增加和线粒体质量的减少。此外，当褪黑激素治疗在SCGx术后4周开始时，它恢复了视觉功能，并扭转了RPE黑色素含量和RPE65免疫反应性的下降。这些发现表明褪黑激素可能成为NE-AMD的一种有前途的安全治疗策略。