EFRI CEE: Engineered Retinal Epigenomics

视网膜盲，如视网膜色素变性（RP）、年龄相关性黄斑变性（AMD）和青光眼（POAG），其特征在于持续的神经元死亡（RP和AMD中的光感受器损失和POAG中的神经节细胞损失）。这些普遍的致盲状况占美国估计1390亿美元的视力障碍年度经济负担的重要部分。该小组首次表明，受控的微尺度电磁（EM）刺激可导致视网膜神经保护性变化。该项目的转型愿景是使用非侵入性受控电刺激来诱导哺乳动物视网膜的遗传变化，以减缓视网膜失明的进展，甚至可能恢复某种程度的视力丧失。这种方法的成功将在基础科学、工程和医学中产生一个全新的领域，并且在这样做的过程中，开发新的、创新的、跨学科的教育计划，这对于培养下一代生物电子设备的研究人员影响保护性遗传变化至关重要。RP中的基因突变、AMD中的脂质代谢异常和炎症以及POAG中的眼内压升高，仅举几例）。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视网膜变化，并暗示神经保护性变化。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，并且可以证明对于某些视网膜失明病症的治疗是关键的。这项提案的愿景是，研究结果将展示如何有效地采用电磁（EM）场刺激来减缓或阻止流行性视网膜疾病的进展。该奖项反映了NSF的法定使命，并通过使用基金会的智力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.