Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India.
Ann Anat. 2019 Nov;226:35-47. doi: 10.1016/j.aanat.2019.06.007. Epub 2019 Jul 19.
Aging of the human retina is accompanied by oxidative stress that exerts profound changes in the retinal neurons. It is unknown if oxidative stress influences the cellular components of the retinal vessels in some ways.
We examined changes in retinal vessels in human donor eyes (age: 35-94 years; N=18) by light and transmission electron microscopy, TUNEL and immunohistochemistry for biomarkers of vascular smooth muscle cells (SMC; actin), oxidative stress (4-hydroxy 2-nonenal [HNE] and nitrotyrosine), microglia (Iba-1) and vessels (isolectin B).
The earliest changes in the endothelium and pericytes of capillaries are apparent from the seventh decade. With aging, there is clear loss of organelles and cytoplasmic filaments, and a progressive thickening of the endothelial and pericyte basal lamina. Loss of filaments, accumulation of lipofuscin and autophagic vacuoles are significant events in aging pericytes and SMC. Actin immunolabelling reveals discontinuity in arterial SMC layers during eighth decade, indicating partial degeneration of SMC. This is followed by hyalinization, with degeneration of the endothelium and SMC in arteries and arterioles of the nerve fibre layer (NFL) and ganglion cell layer in ninth decade. Iba-1 positive microglia were in close contact with the damaged vessels in inner retina, and their cytoplasm was rich in lysosomes. HNE immunoreactivity, but not of nitrotyrosine, was detected in aged vessels from seventh decade onwards, suggesting that lipid peroxidation is a major problem of aged vessels. However, TUNEL positivity seen during this period was limited to few arteries and venules of NFL.
This study shows prominent age-related alterations of the pericytes and SMC of retinal vessels. These changes may limit the energy supply to the neurons and be responsible for age-related loss of neurons of the inner retina.
人类视网膜的衰老伴随着氧化应激，这种应激会对视网膜神经元产生深远的变化。目前尚不清楚氧化应激是否会以某种方式影响视网膜血管的细胞成分。
我们通过光镜和透射电镜、TUNEL 以及血管平滑肌细胞（actin）、氧化应激（4-羟基-2-壬烯醛[HNE]和硝基酪氨酸）、小胶质细胞（Iba-1）和血管（异硫氰酸荧光素 B）的免疫组织化学标志物，检查了人类供体眼中视网膜血管的变化（年龄：35-94 岁；N=18）。
从 70 岁开始，毛细血管内皮细胞和周细胞的早期变化就很明显。随着年龄的增长，细胞器和细胞质细丝明显丢失，内皮细胞和周细胞基底膜逐渐增厚。在衰老的周细胞和血管平滑肌细胞中，细丝丢失、脂褐素和自噬小泡积累是重要事件。在第 8 个十年期间，动脉血管平滑肌层的肌动蛋白免疫标记显示出不连续性，表明血管平滑肌细胞部分退化。随后出现玻璃样变性，在第 9 个十年，神经纤维层（NFL）和节细胞层的动脉和小动脉以及内皮细胞和血管平滑肌细胞发生变性。内视网膜受损血管附近有大量 Iba-1 阳性小胶质细胞，其细胞质富含溶酶体。从第 7 个十年开始，在老年血管中检测到 HNE 免疫反应性，但硝基酪氨酸没有，这表明脂质过氧化是老年血管的主要问题。然而，在此期间，TUNEL 阳性仅限于 NFL 中少数动脉和小静脉。
本研究显示视网膜血管的周细胞和血管平滑肌细胞有明显的年龄相关性改变。这些变化可能会限制神经元的能量供应，并导致内视网膜神经元的年龄相关性丧失。
