Hitching a ride into the retina on nanoparticles called dendrimers offers a new way to treat age-related macular degeneration and retinitis pigmentosa. A collaborative research study among investigators at Wayne State University, the Mayo Clinic and Johns Hopkins Medicine shows that steroids attached to the dendrimers targeted the damage-causing cells associated with neuroinflammation, leaving the rest of the eye unaffected and preserving vision.
The principal authors of the study, Raymond Iezzi, M.D. (Mayo Clinic ophthalmologist) and Rangaramanujam Kannan, Ph.D. (faculty of ophthalmology at The Wilmer Eye Institute of Johns Hopkins) have developed a clinically relevant, targeted, sustained-release drug delivery system using a simple nanodevice construct. The experimental work in rat models was initiated and substantially conducted at Wayne State University, and showed that one intravitreal administration of the nanodevice in microgram quantities could offer neuroprotection at least for a month, and appears in the journal, Biomaterials (33(3), 979-988).
Both dry age-related macular degeneration and retinitis pigmentosa are caused by neuroinflammation, which progressively damages the retina and can lead to blindness. Macular degeneration is the primary cause of vision loss in older Americans, affecting more than 7 million people, according to the National Institutes of Health (NIH). Retinitis pigmentosa encompasses many genetic conditions affecting the retina and impacts 1 in 4,000 Americans, the NIH estimates.
"There is no cure for these diseases, said Iezzi. "An effective treatment could offer hope to hundreds of millions of patients worldwide. We tested the dendrimer delivery system in rats that develop neuroinflammation leading to retinal degeneration. The target was activated microglial cells, the immune cells in charge of cleaning up dead and dying material in the eye. When activated, these cells cause damage via neuroinflammation - a hallmark of each disease."
"Dendrimers are tree-like, non-cytotoxic polymeric drug delivery vehicles (~ 4 nm). Surprisingly, the activated microglia in the degenerating retina appeared to eat the dendrimer selectively and retain them for at least a month. The drug is released from the dendrimer in a sustained fashion inside these cells, offering targeted neuroprotection to the retina," said Kannan.
The treatment reduced neuroinflammation in the rat model and protected vision by preventing injury to photoreceptors in the retina. Although the steroid offers only temporary protection, the treatment as a whole provides sustained relief from neuroinflammation, the study found. The researchers believe that this patent-pending technology with significant translational potential will be advanced further, through this multi-university collaboration among Johns Hopkins, Mayo Clinic and Wayne State.
一种视网膜聚合物纳米技术为患有年龄相关性黄斑变性和色素性视网膜炎的病人提供了一种新的治疗方法。一个来自韦恩州立大学梅奥诊所和约翰斯·霍普金斯实验研究所的合作团队的调查人员表明类固醇附在树枝状damage-causing相关的细胞分子可以保护神经保留残存视力的功效，
首席研究员,雷蒙德Iezzi博士(梅奥诊所的眼科医生)和Rangaramanujam Kannan、博士(教约翰霍普金斯大学Wilmer眼科研究所的眼科教师)已经用一个简单nanodevice建构出来的产物开发出一种与临床相关的,有针对性的、缓释药物递送系统。恩州立大学正发起一种使用几毫克量就可以提供神经保护至少一个月的大鼠模型,实验
年龄相关性黄斑变性和两个干燥患有色素性视网膜炎是由于存在炎症反应,表现为能逐渐损害视网膜,可导致失明。黄斑变性是失明的主要原因在老年美国人,影响了700万多万的人,然而,根据美国国家卫生研究院(NIH)。包括很多患有色素性视网膜炎影响视网膜遗传病和影响1 4000美国人,美国国家卫生研究院估计。
“没有治疗这些疾病。Iezzi说。“一个有效的治疗可以提供希望全世界成千上万的病人。我们验证这样的大 鼠种输送系统开发neuroinflammation导致视网膜变性。目标被激活小胶质细胞的免疫细胞负责清理死亡,死亡资料的眼睛。激活时,这些细胞造成损害的一种标志neuroinflammation——通过每个疾病。”
“是,non-cytotoxic高分子聚合物树药物递送的车辆(~ 4纳米。令人惊讶的是,在活化的小胶质细胞在退化的视网膜出现要吃的有选择地、保留他们种至少要一个月。这个药物是释放持续种时尚这些细胞内部,提供有针对性的对视网膜神经保护,Kannan说。
neuroinflammation治疗降低大鼠模型和保护视力,预防损伤视网膜感光细胞。虽然只提供临时保护类固醇的治疗,作为一个整体来缓解提供持续存在炎症反应,表现为这项研究发现。研究人员认为,这种动态的技术与重大转化能力先进的进一步,通过这种multi-university之间合作的约翰霍普金斯大学,梅奥诊所和鲁尼的状态。 |
