From mouse to human: Accessing the biochemistry of vision in vivo by two-photon excitation

IF 18.6 1区 医学 Q1 OPHTHALMOLOGY Progress in Retinal and Eye Research Pub Date : 2023-03-01 DOI:10.1016/j.preteyeres.2023.101170
Grazyna Palczewska , Maciej Wojtkowski , Krzysztof Palczewski
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引用次数: 4

Abstract

The eye is an ideal organ for imaging by a multi-photon excitation approach, because ocular tissues such as the sclera, cornea, lens and neurosensory retina, are highly transparent to infrared (IR) light. The interface between the retina and the retinal pigment epithelium (RPE) is especially informative, because it reflects the health of the visual (retinoid) cycle and its changes in response to external stress, genetic manipulations, and drug treatments. Vitamin A-derived retinoids, like retinyl esters, are natural fluorophores that respond to multi-photon excitation with near IR light, bypassing the filter-like properties of the cornea, lens, and macular pigments. Also, during natural aging some retinoids form bisretinoids, like diretinoid-pyridiniumethanolamine (A2E), that are highly fluorescent. These bisretinoids appear to be elevated concurrently with aging. Vitamin A-derived retinoids and bisretinoidss are detected by two-photon ophthalmoscopy (2PO), using a new class of light sources with adjustable spatial, temporal, and spectral properties. Furthermore, the two-photon (2P) absorption of IR light by the visual pigments in rod and cone photoreceptors can initiate visual transduction by cis-trans isomerization of retinal, enabling parallel functional studies. Recently we overcame concerns about safety, data interpretation and complexity of the 2P-based instrumentation, the major roadblocks toward advancing this modality to the clinic. These imaging and retina-function assessment advancements have enabled us to conduct the first 2P studies with humans.

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从小鼠到人类:通过双光子激发获得体内视觉的生物化学
眼睛是多光子激发成像的理想器官,因为眼部组织,如巩膜、角膜、晶状体和神经感觉视网膜,对红外光是高度透明的。视网膜和视网膜色素上皮(RPE)之间的界面尤其具有信息性,因为它反映了视觉(类视黄酮)周期的健康状况及其对外部压力、基因操作和药物治疗的反应变化。维生素a衍生的类维甲酸,如视黄醇酯,是天然的荧光团,对近红外光的多光子激发作出反应,绕过角膜、晶状体和黄斑色素的滤光片样特性。此外,在自然衰老过程中,一些类维甲酸形成双维甲酸,如类维甲酸吡啶醇胺(A2E),具有高度荧光性。这些类双维甲酸似乎随着年龄的增长而升高。利用双光子眼科镜(2PO)检测维生素a衍生的类维甲酸和双维甲酸,使用一类具有可调空间、时间和光谱特性的新光源。此外,视杆和视锥中视色素对红外光的双光子(2P)吸收可以通过视网膜的顺反异构化启动视觉转导,从而实现平行功能研究。最近,我们克服了对基于2p的仪器的安全性、数据解释和复杂性的担忧,这些是将这种模式推进到临床的主要障碍。这些成像和视网膜功能评估的进步使我们能够在人类身上进行第一次2P研究。
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来源期刊
CiteScore
34.10
自引率
5.10%
发文量
78
期刊介绍: Progress in Retinal and Eye Research is a Reviews-only journal. By invitation, leading experts write on basic and clinical aspects of the eye in a style appealing to molecular biologists, neuroscientists and physiologists, as well as to vision researchers and ophthalmologists. The journal covers all aspects of eye research, including topics pertaining to the retina and pigment epithelial layer, cornea, tears, lacrimal glands, aqueous humour, iris, ciliary body, trabeculum, lens, vitreous humour and diseases such as dry-eye, inflammation, keratoconus, corneal dystrophy, glaucoma and cataract.
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