Feldman T B, Dontsov A E, Yakovleva M A, Ostrovsky M A
Department of Biology, Lomonosov Moscow State University, Moscow, Russia.
Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia.
Biophys Rev. 2022 Aug 8;14(4):1051-1065. doi: 10.1007/s12551-022-00989-9. eCollection 2022 Aug.
Lipofuscin granules (LGs) are accumulated in the retinal pigment epithelium (RPE) cells. The progressive LG accumulation can somehow lead to pathology and accelerate the aging process. The review examines composition, spectral properties and photoactivity of LGs isolated from the human cadaver eyes. By use of atomic force microscopy and near-field microscopy, we have revealed the fluorescent heterogeneity of LGs. We have discovered the generation of reactive oxygen species by LGs, and found that LGs and melanolipofuscin granules are capable of photoinduced oxidation of lipids. It was shown that A2E, as the main fluorophore (bisretinoid) of LGs, is much less active as an oxidation photosensitizer than other fluorophores (bisretinoids) of LGs. Photooxidized products of bisretinoids pose a much greater danger to the cell than non-oxidized one. Our studies of the fluorescent properties of LGs and their fluorophores (bisretinoids) showed for the first time that their spectral characteristics change (shift to the short-wavelength region) in pathology and after exposure to ionizing radiation. By recording the fluorescence spectra and fluorescence decay kinetics of oxidized products of LG fluorophores, it is possible to improve the methods of early diagnosis of degenerative diseases. Lipofuscin ("aging pigment") is not an inert "slag". The photoactivity of LGs can pose a significant danger to the RPE cells. Fluorescence characteristics of LGs are a tool to detect early stages of degeneration in the retina and RPE.
脂褐素颗粒(LGs)积聚在视网膜色素上皮(RPE)细胞中。LGs的逐渐积聚会以某种方式导致病变并加速衰老过程。这篇综述研究了从人类尸体眼睛中分离出的LGs的组成、光谱特性和光活性。通过使用原子力显微镜和近场显微镜,我们揭示了LGs的荧光异质性。我们发现LGs会产生活性氧物种,并且发现LGs和黑素脂褐素颗粒能够光诱导脂质氧化。结果表明,作为LGs主要荧光团(双视黄醛)的A2E作为氧化光敏剂的活性远低于LGs的其他荧光团(双视黄醛)。双视黄醛的光氧化产物对细胞造成的危害比未氧化的产物大得多。我们对LGs及其荧光团(双视黄醛)荧光特性的研究首次表明,它们的光谱特征在病变和暴露于电离辐射后会发生变化(向短波长区域移动)。通过记录LG荧光团氧化产物的荧光光谱和荧光衰减动力学,有可能改进退行性疾病的早期诊断方法。脂褐素(“衰老色素”)并非惰性的“残渣”。LGs的光活性可能对RPE细胞构成重大危险。LGs的荧光特性是检测视网膜和RPE退变早期阶段的一种工具。