{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:47:19Z","timestamp":1785422839499,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-15-00171"],"award-info":[{"award-number":["24-15-00171"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["24-15-00171"],"award-info":[{"award-number":["24-15-00171"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in older adults. An important challenge is the recognition of its early asymptomatic stages and the monitoring of its progression, which requires reliable biomarkers. Growing evidence indicates that AMD-related biochemical changes are reflected in the proteome of tear fluid (TF). Although TF is a non-invasive and easily collectable diagnostic material, its proteomic analysis is complex and costly and therefore has limited clinical value. Methods: In this pilot single-center retrospective cross-sectional study, we developed a new method for dry AMD screening based on analysis of nano-differential scanning fluorimetry (nanoDSF) tear protein denaturation profiles (TDPs) within 15 min. The TDPs were recorded in representative groups of dry AMD patients (37% early, 48% intermediate, 15% geographic atrophy), and in control groups, including patients with refractive abnormalities (basic control), other retinal degenerative diseases (diabetic retinopathy, peripheral retinal dystrophy), or TF-affecting conditions (dry eye syndrome). High-dimensional TDP data were processed using unsupervised machine learning followed by k-means cluster analysis. Results: The presented pipeline distinguished AMD from the basic control with 74% accuracy and a sensitivity of 0.81 without relying on prior labels. The specificity of AMD detection was confirmed by its effective differentiation from diabetic retinopathy (72%; 0.74), peripheral retinal dystrophy (79%; 0.76) and dry eye disease (76%; 0.81). Classifying the AMD group from the entire population of other patients yielded an accuracy of 71% and a sensitivity of 85%, with a false-negative rate of only 15%. Conclusions: This study is a proof of concept for the nanoDSF-based approach, which can be considered a fast, cost-effective, and convenient tool for population screening for dry AMD, suitable for use in preventive medicine and public health.<\/jats:p>","DOI":"10.3390\/life16071048","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:37:17Z","timestamp":1782279437000},"page":"1048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fast nanoDSF Tear Fluid Profiling: Toward Diagnosis of Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8622-8836","authenticated-orcid":false,"given":"Philipp O.","family":"Tsvetkov","sequence":"first","affiliation":[{"name":"Inst Neurophysiopathol, INP, UMR 7051, Facult\u00e9 des Sciences M\u00e9dicales et Param\u00e9dicales, CNRS, Aix Marseille Univ, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika V.","family":"Tiulina","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1-40 Leninskye Gory, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8143-3606","authenticated-orcid":false,"given":"Elena N.","family":"Iomdina","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6922-0464","authenticated-orcid":false,"given":"Sergey Yu.","family":"Petrov","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2272-0386","authenticated-orcid":false,"given":"Nina Yu.","family":"Kushnarevich","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8444-1054","authenticated-orcid":false,"given":"Elena A.","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga M.","family":"Filippova","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana I.","family":"Markelova","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violetta N.","family":"Papyan","sequence":"additional","affiliation":[{"name":"Helmholtz National Medical Research Center of Eye Diseases, 105062 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timofey A.","family":"Chistyakov","sequence":"additional","affiliation":[{"name":"Endocrinology Research Center, 117292 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton A.","family":"Bougaev","sequence":"additional","affiliation":[{"name":"School of Nuclear Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3372-5015","authenticated-orcid":false,"given":"Natalia G.","family":"Shebardina","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1-40 Leninskye Gory, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8298-2164","authenticated-orcid":false,"given":"Mikhail L.","family":"Shishkin","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1-40 Leninskye Gory, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy V.","family":"Lipatov","sequence":"additional","affiliation":[{"name":"Endocrinology Research Center, 117292 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0137-8585","authenticated-orcid":false,"given":"Dmitry V.","family":"Chistyakov","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1-40 Leninskye Gory, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan I.","family":"Senin","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1-40 Leninskye Gory, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-1983","authenticated-orcid":false,"given":"Vladimir A.","family":"Mitkevich","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3013-7863","authenticated-orcid":false,"given":"Evgeni Yu.","family":"Zernii","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1-40 Leninskye Gory, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1001\/jamaophthalmol.2022.4401","article-title":"Prevalence of Age-Related Macular Degeneration in the US in 2019","volume":"140","author":"Rein","year":"2022","journal-title":"JAMA Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1167\/iovs.66.12.37","article-title":"Reshaping the Burden of nAMD: National, Regional, and Global Prevalence of MNV3 and Its Correlation With Life Expectancy-The RAP Study, Report 7","volume":"66","author":"Gerendas","year":"2025","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rai, B.B., Morley, M.G., Bernstein, P.S., and Maddess, T. (2022). Severity of age-related macular degeneration at first presentation in Bhutan: A 3-year national study. BMC Ophthalmol., 22.","DOI":"10.1186\/s12886-022-02520-w"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1038\/s41433-025-03686-5","article-title":"Burdens and trends of age-related macular degeneration at global, regional, and national levels,1990-2021: Findings from the 2021 global burden of disease study","volume":"39","author":"Zhou","year":"2025","journal-title":"Eye"},{"key":"ref_5","unstructured":"GBD 2021 Global AMD Collaborators (2025). Global burden of vision impairment due to age-related macular degeneration, 1990\u20132021, with forecasts to 2050: A systematic analysis for the Global Burden of Disease Study 2021. Lancet Glob. 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