Noninvasive two-photon optical biopsy of retinal fluorophores

被引：34

作者：

Palczewska, Grazyna ^{[1
,2
]}

Boguslawski, Jakub ^{[3
]}

Stremplewski, Patrycjusz ^{[4
]}

Kornaszewski, Lukasz ^{[3
]}

Zhang, Jianye ^{[2
]}

Dong, Zhiqian ^{[1
,2
]}

Liang, Xiao-Xuan ^{[5
]}

Gratton, Enrico ^{[6
]}

Vogel, Alfred ^{[5
]}

Wojtkowski, Maciej ^{[3
]}

Palczewski, Krzysztof ^{[2
,7
,8
]}

机构：

[1] Polgenix Inc, Dept Med Devices, Cleveland, OH 44106 USA

[2] Univ Calif Irvine, Gavin Herbert Eye Inst, Dept Ophthalmol, Irvine, CA 92697 USA

[3] Polish Acad Sci, Inst Phys Chem, Int Ctr Translat Eye Res, PL-01224 Warsaw, Poland

[4] Nicolaus Copernicus Univ, Fac Phys, PL-87100 Torun, Poland

[5] Univ Lubeck, Inst Biomed Opt, D-23562 Lubeck, Germany

[6] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA

[7] Univ Calif Irvine, Dept Physiol & BioPhys, Irvine, CA 92697 USA

[8] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2020年 / 117卷 / 36期

基金：

欧盟地平线“2020”;

关键词：

eye; retina; two-photon; imaging; RPE; INTERNAL ABSORPTION-COEFFICIENT; SPECTRAL PHASOR ANALYSIS; FLUORESCENCE EXCITATION; PIGMENT EPITHELIUM; LASER; MICROSCOPY; CELLS; AUTOFLUORESCENCE; ACCUMULATION; MECHANISMS;

D O I：

10.1073/pnas.2007527117

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

High-resolution imaging techniques capable of detecting identifiable endogenous fluorophores in the eye along with genetic testing will dramatically improve diagnostic capabilities in the ophthalmology clinic and accelerate the development of new treatments for blinding diseases. Two-photon excitation (TPE)-based imaging overcomes the filtering of ultraviolet light by the lens of the human eye and thus can be utilized to discover defects in vitamin A metabolism during the regeneration of the visual pigments required for the detection of light. Combining TPE with fluorescence lifetime imaging (FLIM) and spectral analyses offers the potential of detecting diseases of the retina at earlier stages before irreversible structural damage has occurred. The main barriers to realizing the benefits of TPE for imaging the human retina arise from concerns about the high light exposure typically needed for informative TPE imaging and the requirement to correlate the ensuing data with different states of health and disease. To overcome these hurdles, we improved TPE efficiency by controlling temporal properties of the excitation light and employed phasor analyses to FLIM and spectral data in mouse models of retinal diseases. Modeling of retinal photo damage revealed that plasma-mediated effects do not play a role and that melanin-related thermal effects are mitigated by reducing pulse repetition frequency. By using noninvasive TPE imaging we identified molecular components of individual granules in the retinal pigment epithelium and present their analytical characteristics.

引用

页码：22532 / 22543

页数：12

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