Histology and clinical imaging lifecycle of black pigment in fibrosis secondary to neovascular age-related macular degeneration.
Histology and clinical imaging lifecycle of black pigment in fibrosis secondary to neovascular age-related macular degeneration.
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DOI：
10.1016/j.exer.2021.108882
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Curcio CA
中科院分区：
文献类型：
--
作者：
Chen L;Cao D;Messinger JD;Ach T;Ferrara D;Freund KB;Curcio CA
患有新生血管性年龄相关性黄斑变性 (nvAMD) 的眼睛中发现了具有大球形黑素体的黑色素细胞，被认为源自视网膜色素上皮 (RPE)。为了生成有关 RPE 参与纤维化的假设，我们将组织学与继发于 nvAMD 的纤维化疤痕中具有明显黑色素的眼睛的临床成像相关联。一名白人女性因右眼 nvAMD 而患有未经治疗的非活动性视网膜下纤维化，9 年来通过彩色眼底摄影 (CFP)、眼底自发荧光 (FAF) 成像和光学相干断层扫描 (OCT) 记录了黄斑发现。死亡后（90 岁），这只食眼准备进行光学和电子显微镜分析，以分析纤维化疤痕中 7 个离散的色素沉着区域。在其他患有 nvAMD 的供体眼睛中，我们确定了黑色素的频率（n = 36 只眼睛）和免疫标记的类维生素A、免疫学和小胶质细胞标记物（RPE65、CD68、Iba1、TMEM119；n = 3 只眼睛）。在对食指眼进行随访时，黑色素在低自发荧光纤维化疤痕内出现并扩大。最黑的区域与黑色素细胞（含有大的球形黑色素体）相关，有些是多层的。苍白区域有稀疏的色素细胞。灰色区域与疤痕中埋藏的 RPE 细胞器和含有稀疏大球形黑素体的多核细胞相关。 94% 的 nvAMD 供体眼睛中可见色素沉着过度。某些黑色素细胞表达一些 RPE65，大部分表达 CD68。在视网膜和疤痕中发现的 Iba1 和 TMEM119 免疫反应性并不与黑色素细胞共定位。 CFP 中的色素沉着过度是由细胞器含量和光学叠加效应造成的。 nvAMD 中的黑色眼底色素很常见，分别对应于含有大量大球形黑素体的细胞和含有稀疏大黑素体的细胞的叠加。黑素细胞在分子上与 RPE 不同，这与转分化过程一致。球形黑素体的亚细胞来源仍有待确定。 nvAMD 眼睛的详细组织学将为未来的研究提供信息，利用空间分辨分子发现技术来产生新的纤维化疗法。黑色素作为纤维化生物标志物的潜力可以在临床多模态成像数据集中进行研究。
Melanotic cells with large spherical melanosomes, thought to originate from retinal pigment epithelium (RPE), are found in eyes with neovascular age-related macular degeneration (nvAMD). To generate hypotheses about RPE participation in fibrosis, we correlate histology to clinical imaging in an eye with prominent black pigment in fibrotic scar secondary to nvAMD. Macular findings in a white woman with untreated inactive subretinal fibrosis due to nvAMD in her right eye were documented over 9 years with color fundus photography (CFP), fundus autofluorescence (FAF) imaging, and optical coherence tomography (OCT). After death (age 90 years), this index eye was prepared for light and electron microscopy to analyze 7 discrete zones of pigmentation in the fibrotic scar. In additional donor eyes with nvAMD, we determined the frequency of black pigment (n = 36 eyes) and immuno-labeled for retinoid, immunologic, and microglial markers (RPE65, CD68, Iba1, TMEM119; n = 3 eyes). During follow-up of the index eye, black pigment appeared and expanded within a hypoautofluorescent fibrotic scar. The blackest areas correlated to melanotic cells (containing large spherical melanosomes), some in multiple layers. Pale areas had sparse pigmented cells. Gray areas correlated to cells with RPE organelles entombed in the scar and multinucleate cells containing sparse large spherical melanosomes. In 94% of nvAMD donor eyes, hyperpigmentation was visible. Certain melanotic cells expressed some RPE65 and mostly CD68. Iba1 and TMEM119 immunoreactivity, found both in retina and scar, did not co-localize with melanotic cells. Hyperpigmentation in CFP results from both organelle content and optical superimposition effects. Black fundus pigment in nvAMD is common and corresponds to cells containing numerous large spherical melanosomes and superimposition of cells containing sparse large melanosomes, respectively. Melanotic cells are molecularly distinct from RPE, consistent with a process of transdifferentiation. The subcellular source of spherical melanosomes remains to be determined. Detailed histology of nvAMD eyes will inform future studies using technologies for spatially resolved molecular discovery to generate new therapies for fibrosis. The potential of black pigment as a biomarker for fibrosis can be investigated in clinical multimodal imaging datasets.
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DOI：
10.1021/jasms.0c00119
发表时间：
2020-12-02
影响因子：
3.2
作者：
Anderson DMG;Messinger JD;Patterson NH;Rivera ES;Kotnala A;Spraggins JM;Caprioli RM;Curcio CA;Schey KL
通讯作者：
Schey KL
影响因子：
4.4
作者：
Bermond, Katharina;Wobbe, Christina;Ach, Thomas
通讯作者：
Ach, Thomas
影响因子：
46.9
作者：
da Cruz, Lyndon;Fynes, Kate;Coffey, Peter J.
通讯作者：
Coffey, Peter J.
影响因子：
4.5
作者：
Chen, Ling;Messinger, Jeffrey D.;Ferrara, Daniela;Freund, K. Bailey;Curcio, Christine A.
通讯作者：
Curcio, Christine A.
DOI：
10.1097/iae.0000000000002771
发表时间：
2020-12-01
影响因子：
3.3
作者：
De Rosa, Irene;Ohayon, Avi;Souied, Eric H.
通讯作者：
Souied, Eric H.