Cakir Bertan, Tomita Yohei, Yagi Hitomi, Romfh Padraic, Allen William, Ko Minji, Chen Peili, Fu Zhongjie, Vakhshoori Daryoosh, Smith Lois E H
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Pendar Technologies, Cambridge, MA 02138, USA.
PNAS Nexus. 2023 May 2;2(5):pgad148. doi: 10.1093/pnasnexus/pgad148. eCollection 2023 May.
Eye diseases are diagnosed by visualizing often irreversible structural changes occurring late in disease progression, such as retinal ganglion cell loss in glaucoma. The retina and optic nerve head have high mitochondrial energy need. Early mitochondrial/energetics dysfunction may predict vulnerability to permanent structural changes. In the in vivo murine eye, we used light-based resonance Raman spectroscopy (RRS) to assess noninvasively the redox states of mitochondria and hemoglobin which reflect availability of electron donors (fuel) and acceptors (oxygen). As proof of principle, we demonstrated that the mitochondrial redox state at the optic nerve head correlates with later retinal ganglion loss after acute intraocular pressure (IOP) elevation. This technology can potentially map the metabolic health of eye tissue in vivo complementary to optical coherence tomography, defining structural changes. Early detection (and normalization) of mitochondrial dysfunction before irreversible damage could lead to prevention of permanent neural loss.
眼部疾病是通过观察疾病进展后期常出现的不可逆结构变化来诊断的，比如青光眼患者视网膜神经节细胞的丧失。视网膜和视神经乳头对线粒体能量需求很高。早期线粒体/能量代谢功能障碍可能预示着易发生永久性结构变化。在活体小鼠眼中，我们使用基于光的共振拉曼光谱（RRS）来无创评估线粒体和血红蛋白的氧化还原状态，这些状态反映了电子供体（燃料）和受体（氧气）的可用性。作为原理验证，我们证明了急性眼压（IOP）升高后，视神经乳头处的线粒体氧化还原状态与后期视网膜神经节细胞的丧失相关。这项技术有可能在体内描绘眼组织的代谢健康状况，作为光学相干断层扫描的补充，以确定结构变化。在不可逆损伤发生之前早期检测（并使其恢复正常）线粒体功能障碍可能会预防永久性神经损伤。
