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dc.contributor.authorSzmacinski, H.
dc.contributor.authorZeng, H.-H.
dc.contributor.authorEslami, K.
dc.contributor.authorPuche, A.C.
dc.contributor.authorThompson, R.B.
dc.date.accessioned2020-05-18T19:43:55Z
dc.date.available2020-05-18T19:43:55Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85083871577&doi=10.1117%2f1.JBO.25.4.047001&partnerID=40&md5=239f6642e47e0d4106bec1db1b204b6e
dc.identifier.urihttp://hdl.handle.net/10713/12768
dc.description.abstractSIGNIFICANCE: Recent evidence suggests that hydroxyapatite (HAP) in sub-retinal pigment epithelial (sub-RPE) deposits in aged human eyes may act to nucleate and contribute to their growth to clinically detectable size. Sub-RPE deposits such as drusen are clinical hallmarks of age-related macular degeneration (AMD), therefore enhanced and earlier detection is a clinical need. We found that tetracycline-family antibiotics, long known to stain HAP in teeth and bones, can also label the HAP in sub-RPE deposits. However, HAP-bound tetracycline fluorescence excitation and emission spectra overlap with the well-known autofluorescence of outer retinal tissues, making them difficult to resolve. AIM: In this initial study, we sought to determine if the HAP-bound tetracyclines also exhibit enhanced fluorescence lifetimes, providing a useful difference in lifetime compared with the short lifetimes observed in vivo in the human retina by the pioneering work of Schweitzer, Zinkernagel, Hammer, and their colleagues, and thus a large enough effect size to resolve the HAP from background by fluorescence lifetime imaging. APPROACH: We stained authentic HAP with tetracyclines and measured the lifetime(s) by phase fluorometry, and stained aged, fixed human cadaver retinas with drusen with selected tetracyclines and imaged them by fluorescence lifetime imaging microscopy (FLIM). RESULTS: We found that chlortetracycline and doxycycline exhibited substantial increase in fluorescence lifetime compared to the free antibiotics and the retinal background, and the drusen were easily resolvable from the retinal background in these specimens by FLIM. CONCLUSIONS: These findings suggest that FLIM imaging of tetracycline (and potentially other molecules) binding to HAP could become a diagnostic tool for the development and progression of AMD.en_US
dc.description.urihttps://doi.org/10.1117/1.JBO.25.4.047001en_US
dc.language.isoen_USen_US
dc.publisherSPIEen_US
dc.relation.ispartofJournal of biomedical optics
dc.subjectage-related macular degenerationen_US
dc.subjectdrusenen_US
dc.subjectfluorescence lifetime imaging microscopyen_US
dc.subjectfluorescence ophthalmoscopyen_US
dc.subjecthydroxyapatiteen_US
dc.subjectretinaen_US
dc.subjectsub-retinal pigment epithelium depositsen_US
dc.subjecttetracyclinesen_US
dc.titleImaging hydroxyapatite in sub-retinal pigment epithelial deposits by fluorescence lifetime imaging microscopy with tetracycline stainingen_US
dc.typeArticleen_US
dc.identifier.doi10.1117/1.JBO.25.4.047001
dc.identifier.pmid32319262


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