Martinez Sofia Mickaela, Inda Ayelen, Ríos Maximiliano Nicolás, Bessone Carolina Del Valle, Bruera Bossio Abril, Guido Mario Eduardo, Luna Pinto José Domingo, Allemandi Daniel Alberto, Quinteros Daniela Alejandra
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina.
Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina.
Pharmaceutics. 2025 Jan 10;17(1):85. doi: 10.3390/pharmaceutics17010085.
BACKGROUND/OBJECTIVES: Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a potent antioxidant with neuroprotective properties; however, it faces limitations such as low solubility. This study proposes the use of human serum albumin nanoparticles (Np-HSA) to enhance the delivery of Mel to the posterior segment of the eye and evaluates its neuroprotective and anti-apoptotic effects on the retina.
A model of retinal degeneration was induced in New Zealand albino rabbits using cytotoxic and oxidative agents. Np-HSA-Mel nanoparticles were administered subconjunctivally, and cellular viability and retinal functionality were assessed using flow cytometry and pupillary light reflex (PLR). Histological and immunohistochemical studies, including the TUNEL assay, were performed to analyse cell survival and apoptotic index.
Np-HSA-Mel significantly preserved pupillary function and cell viability, demonstrating lower apoptosis compared to Mel solution and Np-HSA alone. Histologically, eyes treated with Np-HSA-Mel exhibited fewer structural alterations and greater cellular organisation. The TUNEL assay confirmed a significant reduction in the apoptotic index of retinal ganglion cells (RGCs) treated with Np-HSA-Mel.
Np-HSA-Mel effectively overcame ocular barriers, achieving greater neuroprotective efficacy at the retinal level. These findings highlight the synergistic potential of albumin and Mel in treating neurodegenerative ocular diseases, opening new perspectives for future therapies.
背景/目的：神经退行性眼部疾病，如年龄相关性黄斑变性（AMD）和青光眼，日益引起公众健康关注。氧化应激在其发展过程中起关键作用，损害视网膜细胞并加速疾病进展。褪黑素（Mel）是一种具有神经保护特性的强效抗氧化剂；然而，它存在溶解度低等局限性。本研究提出使用人血清白蛋白纳米颗粒（Np-HSA）来增强Mel向眼后段的递送，并评估其对视网膜的神经保护和抗凋亡作用。
使用细胞毒性和氧化试剂在新西兰白化兔中诱导视网膜变性模型。通过结膜下注射Np-HSA-Mel纳米颗粒，并使用流式细胞术和瞳孔光反射（PLR）评估细胞活力和视网膜功能。进行组织学和免疫组织化学研究，包括TUNEL检测，以分析细胞存活和凋亡指数。
Np-HSA-Mel显著保留了瞳孔功能和细胞活力，与单独的Mel溶液和Np-HSA相比，凋亡率更低。组织学上，用Np-HSA-Mel处理的眼睛结构改变较少，细胞组织更完整。TUNEL检测证实，用Np-HSA-Mel处理的视网膜神经节细胞（RGC）凋亡指数显著降低。
Np-HSA-Mel有效地克服了眼部屏障，在视网膜水平上实现了更大的神经保护功效。这些发现突出了白蛋白和Mel在治疗神经退行性眼部疾病方面的协同潜力，为未来的治疗开辟了新的前景。
