{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:34:43Z","timestamp":1790998483229,"version":"4.1.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009023","name":"PRESTO","doi-asserted-by":"publisher","award":["JPMJPR15P4"],"award-info":[{"award-number":["JPMJPR15P4"]}],"id":[{"id":"10.13039\/501100009023","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Eye diseases are diagnosed by visualizing often irreversible structural changes occurring late in disease progression, such as retinal ganglion cell loss in glaucoma. The retina and optic nerve head have high mitochondrial energy need. Early mitochondrial\/energetics dysfunction may predict vulnerability to permanent structural changes. In the in vivo murine eye, we used light-based resonance Raman spectroscopy (RRS) to assess noninvasively the redox states of mitochondria and hemoglobin which reflect availability of electron donors (fuel) and acceptors (oxygen). As proof of principle, we demonstrated that the mitochondrial redox state at the optic nerve head correlates with later retinal ganglion loss after acute intraocular pressure (IOP) elevation. This technology can potentially map the metabolic health of eye tissue in vivo complementary to optical coherence tomography, defining structural changes. Early detection (and normalization) of mitochondrial dysfunction before irreversible damage could lead to prevention of permanent neural loss.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgad148","type":"journal-article","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T03:18:47Z","timestamp":1682997527000},"source":"Crossref","is-referenced-by-count":4,"title":["In vivo noninvasive mitochondrial redox assessment of the optic nerve head to predict disease"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7789-2738","authenticated-orcid":false,"given":"Bertan","family":"Cakir","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-5737","authenticated-orcid":false,"given":"Yohei","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Yagi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padraic","family":"Romfh","sequence":"additional","affiliation":[{"name":"Pendar Technologies , Cambridge, MA 02138 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minji","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peili","family":"Chen","sequence":"additional","affiliation":[{"name":"Pendar Technologies , Cambridge, MA 02138 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8182-2983","authenticated-orcid":false,"given":"Zhongjie","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryoosh","family":"Vakhshoori","sequence":"additional","affiliation":[{"name":"Pendar Technologies , Cambridge, MA 02138 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7644-6410","authenticated-orcid":false,"given":"Lois E H","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,2]]},"reference":[{"key":"2023072819121669200_pgad148-B1","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.3109\/02713683.2011.607536","article-title":"Mitochondrial dysfunction in retinal diseases","volume":"36","author":"Barot","year":"2011","journal-title":"Curr Eye Res"},{"key":"2023072819121669200_pgad148-B2","doi-asserted-by":"crossref","first-page":"100858","DOI":"10.1016\/j.preteyeres.2020.100858","article-title":"Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration","volume":"79","author":"Kaarniranta","year":"2020","journal-title":"Prog Retin Eye Res"},{"key":"2023072819121669200_pgad148-B3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/jbio.201100087","article-title":"Resonance Raman quantification of the redox state of cytochromes b and c in-vivo and in-vitro","volume":"5","author":"Kakita","year":"2012","journal-title":"J Biophotonics"},{"key":"2023072819121669200_pgad148-B4","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1073\/pnas.69.9.2622","article-title":"Resonance Raman spectra of hemoglobin and cytochrome c: inverse polarization and vibronic scattering","volume":"69","author":"Spiro","year":"1972","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023072819121669200_pgad148-B5","first-page":"31","article-title":"Mitochondrial dysfunction in the aging retina","volume":"8","author":"Eells","year":"2019","journal-title":"Biology (Basel)"},{"key":"2023072819121669200_pgad148-B6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0014-4835(05)80122-8","article-title":"Oxygen consumption in the rat outer and inner retina: light- and pharmacologically-induced inhibition","volume":"61","author":"Medrano","year":"1995","journal-title":"Exp Eye Res"},{"key":"2023072819121669200_pgad148-B7","first-page":"887","article-title":"Glaucoma is second leading cause of blindness globally","volume":"82","author":"Kingman","year":"2004","journal-title":"Bull World Health Organ"},{"key":"2023072819121669200_pgad148-B8","doi-asserted-by":"crossref","first-page":"10515","DOI":"10.1073\/pnas.1509879112","article-title":"In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS","volume":"112","author":"Takihara","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023072819121669200_pgad148-B9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.exer.2017.04.003","article-title":"A mouse ocular explant model that enables the study of living optic nerve head events after acute and chronic intraocular pressure elevation: focusing on retinal ganglion cell axons and mitochondria","volume":"160","author":"Kimball","year":"2017","journal-title":"Exp Eye Res"},{"key":"2023072819121669200_pgad148-B10","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1136\/bjo.83.2.231","article-title":"Histochemical localisation of mitochondrial enzyme activity in human optic nerve and retina","volume":"83","author":"Andrews","year":"1999","journal-title":"Br J Ophthalmol"},{"key":"2023072819121669200_pgad148-B11","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1001\/archopht.1981.03930010650010","article-title":"Rapid axonal transport in primate optic nerve. Distribution of pressure-induced interruption","volume":"99","author":"Radius","year":"1981","journal-title":"Arch Ophthalmol."},{"key":"2023072819121669200_pgad148-B12","doi-asserted-by":"crossref","first-page":"5644","DOI":"10.1523\/JNEUROSCI.5956-09.2010","article-title":"Metabolic vulnerability disposes retinal ganglion cell axons to dysfunction in a model of glaucomatous degeneration","volume":"30","author":"Baltan","year":"2010","journal-title":"J Neurosci"},{"key":"2023072819121669200_pgad148-B13","first-page":"137","article-title":"Chronic experimental glaucoma in primates. II. Effect of extended intraocular pressure elevation on optic nerve head and axonal transport","volume":"19","author":"Quigley","year":"1980","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2023072819121669200_pgad148-B14","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.exer.2005.11.025","article-title":"Optic nerve dynein motor protein distribution changes with intraocular pressure elevation in a rat model of glaucoma","volume":"83","author":"Martin","year":"2006","journal-title":"Exp Eye Res"},{"key":"2023072819121669200_pgad148-B15","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1523\/JNEUROSCI.4443-07.2008","article-title":"Progressive ganglion cell degeneration precedes neuronal loss in a mouse model of glaucoma","volume":"28","author":"Buckingham","year":"2008","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"2023072819121669200_pgad148-B16","doi-asserted-by":"crossref","first-page":"8303","DOI":"10.1167\/iovs.12-10911","article-title":"Anterior and posterior optic nerve head blood flow in nonhuman primate experimental glaucoma model measured by laser speckle imaging technique and microsphere method","volume":"53","author":"Wang","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2023072819121669200_pgad148-B17","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1167\/iovs.11-8429","article-title":"Magnetic resonance imaging indicates decreased choroidal and retinal blood flow in the DBA\/2J mouse model of glaucoma","volume":"53","author":"Lavery","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2023072819121669200_pgad148-B18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0895-7061(00)01285-1","article-title":"Comparison of arterial blood pressure in different strains of mice","volume":"14","author":"Mattson","year":"2001","journal-title":"Am J Hypertens"},{"issue":"408","key":"2023072819121669200_pgad148-B19","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aan0117","article-title":"Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest","volume":"9","author":"Perry","year":"2017","journal-title":"Sci Transl Med"},{"key":"2023072819121669200_pgad148-B20","doi-asserted-by":"crossref","first-page":"6149","DOI":"10.1021\/bi027387y","article-title":"Resonance Raman investigations of cytochrome c conformational change upon interaction with the membranes of intact and Ca2+-exposed mitochondria","volume":"42","author":"Berezhna","year":"2003","journal-title":"Biochemistry"},{"key":"2023072819121669200_pgad148-B21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0014-5793(77)80438-9","article-title":"Spectral evidence for interactions between membrane-bound hemes: resonance Raman spectra of mitochondrial cytochrome b\u2013c1 complex as a function of redox potential","volume":"80","author":"Adar","year":"1977","journal-title":"FEBS Lett"},{"key":"2023072819121669200_pgad148-B22","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1039\/C8AN02213E","article-title":"Using redox-sensitive mitochondrial cytochrome Raman bands for label-free detection of mitochondrial dysfunction","volume":"144","author":"Morimoto","year":"2019","journal-title":"Analyst."}],"container-title":["PNAS Nexus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pnasnexus\/advance-article-pdf\/doi\/10.1093\/pnasnexus\/pgad148\/50152713\/pgad148.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/2\/5\/pgad148\/51002109\/pgad148.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/2\/5\/pgad148\/51002109\/pgad148.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T15:14:18Z","timestamp":1690557258000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article\/doi\/10.1093\/pnasnexus\/pgad148\/7147608"}},"subtitle":[],"editor":[{"given":"Andrey","family":"Abramov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5,2]]}},"URL":"https:\/\/doi.org\/10.1093\/pnasnexus\/pgad148","relation":{},"ISSN":["2752-6542"],"issn-type":[{"value":"2752-6542","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,5]]},"published":{"date-parts":[[2023,5]]},"article-number":"pgad148"}}