In vivo imaging of the human eye using a 2-photon-excited fluorescence scanning laser ophthalmoscope.
Medical devices
Ophthalmology
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
18 01 2022
18 01 2022
Historique:
received:
18
08
2021
accepted:
24
11
2021
pubmed:
1
12
2021
medline:
19
2
2022
entrez:
30
11
2021
Statut:
ppublish
Résumé
BackgroundNoninvasive assessment of metabolic processes that sustain regeneration of human retinal visual pigments (visual cycle) is essential to improve ophthalmic diagnostics and to accelerate development of new treatments to counter retinal diseases. Fluorescent vitamin A derivatives, which are the chemical intermediates of these processes, are highly sensitive to UV light; thus, safe analyses of these processes in humans are currently beyond the reach of even the most modern ocular imaging modalities.MethodsWe present a compact, 2-photon-excited fluorescence scanning laser ophthalmoscope and spectrally resolved images of the human retina based on 2-photon excitation (TPE) with near-infrared light. A custom Er:fiber laser with integrated pulse selection, along with intelligent postprocessing of data, enables excitation with low laser power and precise measurement of weak signals.ResultsWe demonstrate spectrally resolved TPE fundus images of human subjects. Comparison of TPE data between human and mouse models of retinal diseases revealed similarity with mouse models that rapidly accumulate bisretinoid condensation products. Thus, visual cycle intermediates and toxic byproducts of this metabolic pathway can be measured and quantified by TPE imaging.ConclusionOur work establishes a TPE instrument and measurement method for noninvasive metabolic assessment of the human retina. This approach opens the possibility for monitoring eye diseases in the earliest stages before structural damage to the retina occurs.FundingNIH, Research to Prevent Blindness, Foundation for Polish Science, European Regional Development Fund, Polish National Agency for Academic Exchange, and Polish Ministry of Science and Higher Education.
Identifiants
pubmed: 34847075
pii: 154218
doi: 10.1172/JCI154218
pmc: PMC8759795
doi:
pii:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Opt Lett. 2012 Jun 15;37(12):2316-8
pubmed: 22739893
Exp Eye Res. 2010 Mar;90(3):382-7
pubmed: 19925789
Biomed Opt Express. 2015 Feb 26;6(3):1055-66
pubmed: 25798325
J Biol Chem. 2011 May 13;286(19):17248-58
pubmed: 21454509
Invest Ophthalmol Vis Sci. 2016 Feb;57(2):647-57
pubmed: 26903225
Nat Biomed Eng. 2021 Feb;5(2):169-178
pubmed: 33077938
J Biomed Opt. 2004 Nov-Dec;9(6):1265-70
pubmed: 15568947
Biomed Opt Express. 2020 Jul 20;11(8):4431-4442
pubmed: 32923054
Eye (Lond). 2016 Feb;30(2):241-6
pubmed: 26768915
Invest Ophthalmol Vis Sci. 2016 Feb;57(2):632-46
pubmed: 26903224
Invest Ophthalmol Vis Sci. 2020 Sep 1;61(11):34
pubmed: 32945842
Transl Vis Sci Technol. 2021 Feb 5;10(2):11
pubmed: 34003895
Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3556-64
pubmed: 16877429
Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):19629-19638
pubmed: 32759209
Nat Biotechnol. 2003 Nov;21(11):1369-77
pubmed: 14595365
Am J Ophthalmol. 2018 May;189:127-138
pubmed: 29477964
J Opt Soc Am A Opt Image Sci Vis. 2007 May;24(5):1457-67
pubmed: 17429493
Biomed Opt Express. 2020 Sep 15;11(10):5586-5602
pubmed: 33149973
Expert Opin Orphan Drugs. 2015 May 4;3(5):563-575
pubmed: 26246977
Appl Opt. 1987 Apr 15;26(8):1492-9
pubmed: 20454349
Br J Ophthalmol. 1999 Jul;83(7):867-77
pubmed: 10381676
Nat Med. 2010 Dec;16(12):1444-9
pubmed: 21076393
Vision Res. 2003 Dec;43(28):2983-90
pubmed: 14611934
Nat Genet. 1998 Dec;20(4):344-51
pubmed: 9843205
J Opt Soc Am A Opt Image Sci Vis. 2003 Nov;20(11):2010-5
pubmed: 14620328
Biomed Opt Express. 2016 Nov 16;7(12):5148-5169
pubmed: 28018732
Vision Res. 2000;40(18):2467-73
pubmed: 10915886
Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):E5445-54
pubmed: 25453064
JCI Insight. 2018 Sep 6;3(17):
pubmed: 30185665
Nat Med. 2014 Jul;20(7):785-9
pubmed: 24952647
J Opt Soc Am A Opt Image Sci Vis. 2007 May;24(5):1250-65
pubmed: 17429471
Science. 1990 Apr 6;248(4951):73-6
pubmed: 2321027
Opt Lett. 2002 Aug 15;27(16):1415-7
pubmed: 18026464
Int J Environ Res Public Health. 2005 Apr;2(1):147-55
pubmed: 16705812
J Biol Chem. 2008 Sep 26;283(39):26684-93
pubmed: 18658157
Prog Retin Eye Res. 2017 Sep;60:120-143
pubmed: 28673870
Microsc Res Tech. 2007 May;70(5):410-9
pubmed: 17393496
Invest Ophthalmol Vis Sci. 1995 Mar;36(3):718-29
pubmed: 7890502
Invest Ophthalmol Vis Sci. 2014 May 20;55(6):3929-38
pubmed: 24845640
Proc Natl Acad Sci U S A. 2016 Jun 21;113(25):6904-9
pubmed: 27274068
Methods Enzymol. 2000;316:313-24
pubmed: 10800683
Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22532-22543
pubmed: 32848058
J Biol Chem. 2013 Nov 29;288(48):34484-93
pubmed: 24129572
J Cell Biol. 2004 Feb 2;164(3):373-83
pubmed: 14745001
J Neurosci. 2001 Jan 1;21(1):53-8
pubmed: 11150319
Invest Ophthalmol Vis Sci. 2014 Jun 26;55(7):4438-47
pubmed: 24970255
Opt Lett. 2006 Jun 1;31(11):1684-6
pubmed: 16688261
Proc Natl Acad Sci U S A. 2005 May 17;102(20):7091-6
pubmed: 15870200
Invest Ophthalmol Vis Sci. 2000 Feb;41(2):337-48
pubmed: 10670460
J Biomed Opt. 2008 Mar-Apr;13(2):024008
pubmed: 18465971
Biomed Opt Express. 2019 Aug 09;10(9):4551-4567
pubmed: 31565509
Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1855-66
pubmed: 11431454