EFRI CEE: Engineered Retinal Epigenomics

视网膜失明，如色素性视网膜炎（RP）、年龄相关性黄斑变性（AMD）和青光眼（POAG），其特征是持续的神经元死亡（RP和AMD的光感受器丧失和POAG的神经节细胞丧失）。这些普遍的致盲状况占美国视力障碍每年约1390亿美元经济负担的很大一部分。该小组首次表明，受控的微电磁（EM）刺激可导致视网膜的神经保护变化。这个项目的转型愿景是使用非侵入性控制电刺激来诱导哺乳动物视网膜的基因变化，以减缓视网膜失明的进展，甚至可能恢复某种程度上失去的视力。这种方法的成功将在基础科学、工程和医学领域催生一个全新的领域，并在此过程中开发出新的、创新的、跨学科的教育项目，对培养下一代生物电子设备研究人员至关重要，这些研究人员可以影响保护性基因变化。关于为什么神经元死亡发生在不同的视网膜致盲疾病（例如，RP的基因突变，AMD的脂质代谢异常和炎症，POAG的眼压升高等等），已经确定了许多机制。该小组已经表明，受控的微尺度电磁（EM）刺激可以导致表观遗传性视网膜变化，并影响神经保护变化。该提议的假设是，通过受控电刺激诱导的视网膜的神经表观遗传和染色质重塑是神经保护的关键分子决定因素，并且可能被证明是治疗某些视网膜失明条件的关键。这项提议的愿景是，这些发现将证明如何使用电磁场刺激可以有效地采用减缓或停止流行的视网膜疾病的进展。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Retinal blindness, such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and glaucoma (POAG), is characterized by unrelenting neuronal death (photoreceptor loss in RP and AMD and ganglion cell loss in POAG). These prevalent blinding conditions account for a significant part of the estimated US$139 billion annual economic burden of vision disorders in the U.S. This group has, for the first time, shown that controlled microscale electromagnetic (EM) stimulation can lead to neuroprotective changes in the retina. The transformational vision of this project is to use non-invasive controlled electrical stimulation to induce genetic changes in the mammalian retina to slow down the progression of retinal blindness and perhaps even restore some level of the lost vision. The success of such an approach would spawn a whole new area in basic science, engineering, and medicine and in doing so develop new, innovative, cross-disciplinary educational programs critical to foster the next-generation of researchers of bioelectronic devices to affect protective genetic changes.A number of mechanisms have been identified as to why neuronal death occurs in different retinal blinding disorders (e.g., genetic mutations in RP, lipid metabolism abnormalities and inflammation in AMD, and elevated intraocular pressure in POAG to name a few). This group has shown that controlled microscale electromagnetic (EM) stimulation can lead to epigenetic retinal changes with implications for neuroprotective changes. The hypothesis of this proposal is that neuroepigenetic and chromatin remodeling of the retina induced through controlled electrical stimulation is a key molecular determinant of neuroprotection and could prove to be pivotal for the treatment of certain retinal blindness conditions. The vision of this proposal is that the findings will demonstrate how stimulation using electromagnetic (EM) fields can be effectively adopted to slow or halt the progression of prevalent retinal diseases.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.