EFRI CEE: Engineered Retinal Epigenomics

视网膜失明，如视网膜色素变性(RP)、老年性黄斑变性(AMD)和青光眼(POAG)，以神经元的持续死亡(RP和AMD的光感受器丢失和POAG的神经节细胞丢失)为特征。据估计，美国每年因视力障碍造成的经济负担约为1390亿美元，而这些普遍的失明疾病占了很大一部分。该组织首次证明，受控的微尺度电磁(EM)刺激可以导致视网膜的神经保护变化。该项目的变革性视觉是使用非侵入性可控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的失明。这种方法的成功将在基础科学、工程学和医学领域催生一个全新的领域，并由此开发出新的、创新的、跨学科的教育项目，这些项目对于培养下一代生物电子设备研究人员影响保护性基因变化至关重要。关于为什么神经元死亡发生在不同的视网膜致盲疾病中(例如，RP的基因突变、AMD的脂代谢异常和炎症以及POAG的眼压升高等)，已经确定了一些机制。该小组已经证明，受控的微尺度电磁(EM)刺激可以导致表观遗传性视网膜改变，并暗示神经保护改变。这一建议的假设是，通过受控电刺激诱导的视网膜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，可能被证明在某些视网膜失明疾病的治疗中起关键作用。这项提案的愿景是，研究结果将展示如何有效地采用电磁场刺激来减缓或阻止流行的视网膜疾病的进展。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.