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Changes in the density of melanosomes and lipofuscin in RPE cells are considered hallmarks of various retinal diseases, including Stargardt disease and age-related macular degeneration (AMD). Herein, we report the potential of an in vivo multimodal imaging technique based on directional back-scattering and short-wavelength fundus autofluorescence (SW-FAF) to study disease-related changes in the density of melanosomes and lipofuscin granules in RPE cells. Changes in the concentration of these granules in\n                    <jats:italic>Abca4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice (a model of Stargardt disease) relative to age-matched wild-type (WT) controls were investigated. Directional optical coherence tomography (dOCT) was used to assess melanosome density in vivo, whereas the autofluorescence (AF) images and emission spectra acquired with a spectrometer-integrated scanning laser ophthalmoscope (SLO) were used to characterize lipofuscin and melanolipofuscin granules in the same RPE region. Subcellular-resolution ex vivo imaging using confocal fluorescence microscopy and electron microscopy was performed on the same tissue region to visualize and quantify melanosomes, lipofuscin, and melanolipofuscin granules. Comparisons between in vivo and ex vivo results confirmed an increased concentration of lipofuscin granules and decreased concentration of melanosomes in the RPE of\n                    <jats:italic>Abca4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, and provided an explanation for the differences in fluorescence and directionality of RPE scattering observed in vivo between the two mouse strains.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-95320-z","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T06:03:10Z","timestamp":1628575390000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["In vivo multimodal retinal imaging of disease-related pigmentary changes in retinal pigment epithelium"],"prefix":"10.1038","volume":"11","author":[{"given":"Ratheesh K.","family":"Meleppat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitryn E.","family":"Ronning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Karlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie E.","family":"Burns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Edward N.","family":"Pugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Zawadzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"95320_CR1","doi-asserted-by":"publisher","first-page":"802","DOI":"10.2174\/156652410793937813","volume":"10","author":"JR Sparrrow","year":"2010","unstructured":"Sparrrow, J. R., Hicks, D. & Hamel, C. P. The retinal pigment epithelium in health and disease. Curr. Mol. Med. 10, 802\u2013823. https:\/\/doi.org\/10.2174\/156652410793937813 (2010).","journal-title":"Curr. Mol. Med."},{"key":"95320_CR2","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1111\/ceo.13834","volume":"48","author":"S Somasundaran","year":"2020","unstructured":"Somasundaran, S., Constable, I. J., Mellough, C. B. & Carvalho, L. S. Retinal pigment epithelium and age-related macular degeneration: a review of major disease mechanisms. Clin. Exp. Ophthalmol. 48, 1043\u20131056. https:\/\/doi.org\/10.1111\/ceo.13834 (2020).","journal-title":"Clin. Exp. Ophthalmol."},{"key":"95320_CR3","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/S0167-4943(02)00005-5","volume":"34","author":"ML Katz","year":"2002","unstructured":"Katz, M. L. & Robison, W. G. What is lipofuscin? Defining characteristics and differentiation from other autofluorescent lysosomal storage bodies. 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