Retinal Remodeling and Metabolic Alterations in Human AMD.
Retinal Remodeling and Metabolic Alterations in Human AMD.
复制标题
DOI：
10.3389/fncel.2016.00103
复制
发表时间：
2016
影响因子：
5.3
通讯作者：
Marc RE
中科院分区：
文献类型：
--
作者：
Jones BW;Pfeiffer RL;Ferrell WD;Watt CB;Tucker J;Marc RE
视网膜相关性黄斑变性（AMD）是一种进行性视网膜变性，导致中央视野丧失，最终导致衰弱性失明。AMD影响18%的65至74岁的美国人，30%的年龄超过74岁，并且是西方人群中严重视力丧失和失明的主要原因。虽然已知许多遗传和环境风险因素导致AMD，但我们目前对介导疾病进展的机制知之甚少。遗传和非遗传风险因素调节AMD发病机制的途径和机制仍在很大程度上尚未探索。此外，目前对AMD的治疗是姑息性的并且限于湿性/渗出性形式。视网膜是一种复杂的异质细胞组织，大多数视网膜细胞类别在AMD中受到影响或改变。确定AMD的疾病和阶段特异性细胞结构和代谢反应对于突出干预目标至关重要。本文的目的是说明AMD中受影响的细胞类型，并证明这些变化的影响，可能始于视网膜色素上皮（RPE），用于神经视网膜的重塑。跟踪疾病进展中的异源细胞反应最好通过计算分子表型（CMP）实现，CMP是一种能够为视网膜中的每个细胞获取小分子指纹的工具。CMP揭示了进行性视网膜变性如视网膜色素变性（RP）中的关键细胞和分子病理（重塑和重编程）。我们现在将这些方法应用于正常人和AMD组织，绘制AMD视网膜中细胞和分子变化的进展，包括疾病的晚期形式。
Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease.