Multiple Bioenergy-Linked OCT Biomarkers Suggest Greater-Than-Normal Rod Mitochondria Activity Early in Experimental Alzheimer's Disease.
Multiple Bioenergy-Linked OCT Biomarkers Suggest Greater-Than-Normal Rod Mitochondria Activity Early in Experimental Alzheimer's Disease.
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DOI：
10.1167/iovs.64.3.12
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发表时间：
2023-03-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
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在阿尔茨海默病中，中枢大脑神经元显示出早期过度活跃的证据。目前尚不清楚这种情况是否发生在另一个疾病目标视网膜中。在这里，我们测试了实验性阿尔茨海默病体内杆状线粒体前驱过度活跃的成像生物标志物表现。使用光学相干断层扫描 (OCT) 对 C57BL/6J 背景下的光适应和暗适应 4 个月大 5xFAD 和野生型 (WT) 小鼠进行了研究。我们测量了内段椭球区（EZ）的反射率轮廓形状作为线粒体分布的代表。还测量了对线粒体活性敏感的另外两个指标：外界膜-视网膜色素上皮 (ELM-RPE) 区域的厚度以及感光器尖端和顶端 RPE 之间的低反射带 (HB) 的信号强度。评估视网膜层状厚度和视觉性能。为了应对低能量需求（光），WT 小鼠表现出预期的 EZ 反射率轮廓形状伸长、相对较厚的 ELM-RPE 和更大的 HB 信号。在高能量需求（黑暗）下，EZ反射率轮廓形状更圆，ELM-RPE更薄，HB降低。光适应 5xFAD 小鼠的这些 OCT 生物标志物模式与光适应 WT 小鼠的模式不匹配，而是与暗适应 WT 小鼠的模式匹配。暗适应 5xFAD 和 WT 小鼠表现出相同的生物标志物模式。 5xFAD 小鼠表现出适度的核层变薄和低于正常的对比敏感度。三种 OCT 生物能源生物标志物的结果提出了常见阿尔茨海默病模型中体内早期视杆细胞过度活跃的新可能性。
In Alzheimer's disease, central brain neurons show evidence for early hyperactivity. It is unclear if this occurs in the retina, another disease target. Here, we tested for imaging biomarker manifestation of prodromal hyperactivity in rod mitochondria in vivo in experimental Alzheimer's disease. Light- and dark-adapted 4-month-old 5xFAD and wild-type (WT) mice, both on a C57BL/6J background, were studied with optical coherence tomography (OCT). We measured the reflectivity profile shape of the inner segment ellipsoid zone (EZ) as a proxy for mitochondria distribution. Two additional indices responsive to mitochondria activity were also measured: the thickness of the external limiting membrane–retinal pigment epithelium (ELM-RPE) region and the signal magnitude of a hyporeflective band (HB) between photoreceptor tips and apical RPE. Retinal laminar thickness and visual performance were evaluated. In response to low energy demand (light), WT mice showed the expected elongation in EZ reflectivity profile shape, relatively thicker ELM-RPE, and greater HB signal. Under high energy demand (dark), the EZ reflectivity profile shape was rounder, the ELM-RPE was thinner, and the HB was reduced. These OCT biomarker patterns for light-adapted 5xFAD mice did not match those of light-adapted WT mice but rather that of dark-adapted WT mice. Dark-adapted 5xFAD and WT mice showed the same biomarker pattern. The 5xFAD mice exhibited modest nuclear layer thinning and lower-than-normal contrast sensitivity. Results from three OCT bioenergy biomarkers raise the novel possibility of early rod hyperactivity in vivo in a common Alzheimer's disease model.
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影响因子：
5.3
作者：
Aung, Moe H.;Park, Han Na;Pardue, Machelle T.
通讯作者：
Pardue, Machelle T.
影响因子：
4.4
作者：
Berkowitz BA;Podolsky RH;Childers KL;Roche SL;Cotter TG;Graffice E;Harp L;Sinan K;Berri AM;Schneider M;Qian H;Gao S;Roberts R
通讯作者：
Roberts R
影响因子：
4.4
作者：
通讯作者：
--
影响因子：
1.4
作者：
CRONINGOLOMB, A;CORKIN, S;GROWDON, JH
通讯作者：
GROWDON, JH
影响因子：
4.4
作者：
Berkowitz BA;Podolsky RH;Lenning J;Khetarpal N;Tran C;Wu JY;Berri AM;Dernay K;Shafie-Khorassani F;Roberts R
通讯作者：
Roberts R