{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:19:19Z","timestamp":1789712359265,"version":"4.0.1"},"reference-count":85,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential functions of trehalose in oxidative stress, protein clearance, and inflammation, with an emphasis on animal models and clinical trials in ophthalmology. The main objective is to help understand the beneficial effects of trehalose in clinical trials and practice, especially in patients suffering from ocular surface disease. The discussion is supplemented with an overview of patents for the use of trehalose in dry eye and with prospects for the 2020s.<\/jats:p>","DOI":"10.3390\/biom10050809","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T11:42:02Z","timestamp":1590406922000},"page":"809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Trehalose for Ocular Surface Health"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-0303","authenticated-orcid":false,"given":"Jarmo","family":"Laihia","sequence":"first","affiliation":[{"name":"Finnsusp Ltd., P\u00e4\u00e4skykalliontie 5, FI-21420 Lieto, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kaarniranta","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, FI-70210 Kuopio, Finland"},{"name":"Department of Ophthalmology, Kuopio University Hospital, FI-70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"ref_1","unstructured":"(2020, April 02). National Center for Biotechnology Information, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=trehalose."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/jlac.18320010202","article-title":"Untersuchung \u00fcber das Mutterkorn, Secale cornutum","volume":"1","author":"Wiggers","year":"1832","journal-title":"Annalen der Pharmacie"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/S0278-6915(02)00011-X","article-title":"Trehalose: A review of properties, history of use and human tolerance, and results of multiple safety studies","volume":"40","author":"Richards","year":"2002","journal-title":"Food Chem. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1007\/s00253-018-8814-y","article-title":"Biotechnical production of trehalose through the trehalose synthase pathway: Current status and future prospects","volume":"102","author":"Cai","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1002\/jps.22458","article-title":"Trehalose: Current Use and Future Applications","volume":"100","author":"Ohtake","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1007\/s00417-011-1676-y","article-title":"Favorable effects of trehalose on the development of UVB-mediated antioxidant\/pro-oxidant imbalance in the corneal epithelium, proinflammatory cytokine and matrix metalloproteinase induction, and heat shock protein 70 expression","volume":"249","author":"Ardan","year":"2011","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_7","first-page":"1029","article-title":"Trehalose treatment accelerates the healing of UVB-irradiated corneas. Comparative immunohistochemical studies on corneal cryostat sections and corneal impression cytology","volume":"27","author":"Luyckx","year":"2012","journal-title":"Histol. Histopathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1857086-10","DOI":"10.1155\/2019\/1857086","article-title":"The Healing of Oxidative Injuries with Trehalose in UVB-Irradiated Rabbit Corneas","volume":"2019","author":"Cejka","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jvs.2013.06.078","article-title":"Trehalose protects against spinal cord ischemia in rabbits","volume":"60","author":"Takahashi","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Portbury, S.D., Hare, D.J., Finkelstein, D.I., and Adlard, P.A. (2017). Trehalose improves traumatic brain injury-induced cognitive impairment. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183683"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1039\/C8MT00068A","article-title":"Trehalose elevates brain zinc levels following controlled cortical impact in a mouse model of traumatic brain injury","volume":"10","author":"Portbury","year":"2018","journal-title":"Metallomics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1039\/C3MT00291H","article-title":"Recent advances in the understanding of the role of zinc in ocular tissues","volume":"6","author":"Ugarte","year":"2014","journal-title":"Metallomics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3340","DOI":"10.1073\/pnas.0905437106","article-title":"Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury","volume":"Volume 107","author":"Lee","year":"2010","journal-title":"Proceedings of the National Academy of Sciences, Massachusetts Institute of Technology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ijpharm.2012.01.035","article-title":"In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury","volume":"426","author":"Stanwick","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s12035-015-9235-x","article-title":"PLGA Nanoparticles Loaded Cerebrolysin: Studies on Their Preparation and Investigation of the Effect of Storage and Serum Stability with Reference to Traumatic Brain Injury","volume":"52","author":"Ruozi","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.burns.2014.09.022","article-title":"Feasibility study of an active wound dressing based on hollow fiber membranes in a porcine wound model","volume":"41","author":"Plettig","year":"2015","journal-title":"Burns"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7414","DOI":"10.1021\/acs.langmuir.8b02015","article-title":"Intracellular Delivery of Trehalose for Cell Banking","volume":"35","author":"Stewart","year":"2018","journal-title":"Langmuir"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/btpr.2399","article-title":"Combining endocytic and freezing-induced trehalose uptake for cryopreservation of mammalian cells","volume":"33","author":"Zhang","year":"2017","journal-title":"Biotechnol. Prog."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep38586","article-title":"SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy","volume":"6","author":"Mayer","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1093\/icb\/45.5.810","article-title":"Stabilization of Dry Mammalian Cells: Lessons from Nature","volume":"45","author":"Crowe","year":"2005","journal-title":"Integr. Comp. Boil."},{"key":"ref_21","first-page":"1","article-title":"Trehalose-Based Eye Drops Preserve Viability and Functionality of Cultured Human Corneal Epithelial Cells during Desiccation","volume":"2014","author":"Marycz","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"505","DOI":"10.5935\/0004-2749.20180100","article-title":"Effect of the bioprotectant agent trehalose on corneal epithelial healing after corneal cross-linking for keratoconus","volume":"81","author":"Ozek","year":"2018","journal-title":"Arq. Bras. de Oftalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/717835","article-title":"Protective Effects of Trehalose on the Corneal Epithelial Cells","volume":"2014","author":"Aragona","year":"2014","journal-title":"Sci. World J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4093","DOI":"10.2147\/IJN.S105606","article-title":"Influence of freeze-drying and \u03b3-irradiation in preclinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using d-(+)-trehalose and polyethylene glycol","volume":"11","author":"Yacasi","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_25","first-page":"1403","article-title":"Reduced UVB-induced corneal damage caused by reactive oxygen and nitrogen species and decreased changes in corneal optics after trehalose treatment","volume":"25","author":"Ardan","year":"2010","journal-title":"Histol. Histopathol."},{"key":"ref_26","first-page":"921","article-title":"A novel proteotoxic stress associated mechanism for macular corneal dystrophy","volume":"30","author":"Kaarniranta","year":"2015","journal-title":"Histol. Histopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/femsyr\/foy058","article-title":"Discrete roles of trehalose and Hsp104 in inhibition of protein aggregation in yeast cells","volume":"18","author":"Sethi","year":"2018","journal-title":"FEMS Yeast Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s10571-005-8474-1","article-title":"Protein Aggregation in Retinal Cells and Approaches to Cell Protection","volume":"25","author":"Surgucheva","year":"2005","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Blasiak, J., Pawlowska, E., Szczepanska, J., and Kaarniranta, K. (2019). Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010210"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1096\/fj.14-268904","article-title":"Nrf2 protects mitochondrial decay by oxidative stress","volume":"30","author":"Strom","year":"2015","journal-title":"FASEB J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.arr.2018.06.003","article-title":"Nrf2: Molecular and epigenetic regulation during aging","volume":"47","author":"Zazueta","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.redox.2018.09.011","article-title":"Loss of NRF-2 and PGC-1\u03b1 genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration","volume":"20","author":"Felszeghy","year":"2019","journal-title":"Redox Boil."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.redox.2017.09.007","article-title":"Trehalose protects against oxidative stress by regulating the Keap1\u2013Nrf2 and autophagy pathways","volume":"15","author":"Mizunoe","year":"2018","journal-title":"Redox Boil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1080\/15548627.2015.1061170","article-title":"The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells","volume":"11","author":"Johansson","year":"2015","journal-title":"Autophagy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6857","DOI":"10.1007\/s12035-016-0196-5","article-title":"Trehalose Inhibits Protein Aggregation Caused by Transient Ischemic Insults Through Preservation of Proteasome Activity, Not via Induction of Autophagy","volume":"54","author":"Li","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_36","first-page":"24261","article-title":"Trehalose Accumulation during Cellular Stress Protects Cells and Cellular Proteins from Damage by Oxygen Radicals","volume":"276","author":"Benaroudj","year":"2001","journal-title":"J. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jtos.2019.01.008","article-title":"Autophagy in corneal health and disease: A concise review","volume":"17","author":"Martin","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1084\/jem.20150956","article-title":"Therapeutic targeting of autophagy in neurodegenerative and infectious diseases","volume":"212","author":"Rubinsztein","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Byun, S., Lee, E., and Lee, Y. (2017). Therapeutic Implications of Autophagy Inducers in Immunological Disorders, Infection, and Cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091959"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2174\/1389450115666140225104705","article-title":"Can trehalose prevent neurodegeneration? Insights from experimental studies","volume":"15","author":"Emanuele","year":"2014","journal-title":"Curr. Drug Targets"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"fs2","DOI":"10.1126\/scisignal.aaf1937","article-title":"Mystery solved: Trehalose kickstarts autophagy by blocking glucose transport","volume":"9","author":"Mardones","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/nrcardio.2017.97","article-title":"Atherosclerosis: Trehalose induces macrophage autophagy-lysosomal biogenesis","volume":"14","author":"Huynh","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.jtos.2019.08.004","article-title":"Trehalose augments autophagy to mitigate stress induced inflammation in human corneal cells","volume":"17","author":"Panigrahi","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1007\/s12640-014-9487-7","article-title":"Trehalose Alleviates PC12 Neuronal Death Mediated by Lipopolysaccharide-Stimulated BV-2 Cells via Inhibiting Nuclear Transcription Factor NF-\u03baB and AP-1 Activation","volume":"26","author":"He","year":"2014","journal-title":"Neurotox. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1080\/15548627.2018.1474313","article-title":"Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency","volume":"14","author":"Lotfi","year":"2018","journal-title":"Autophagy"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jtos.2017.05.002","article-title":"TFOS DEWS II pain and sensation report","volume":"15","author":"Belmonte","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1263\/jbb.106.610","article-title":"Vitrification of Corneal Endothelial Cells in a Monolayer","volume":"106","author":"Fan","year":"2008","journal-title":"J. Biosci. Bioeng."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1016\/j.biomaterials.2008.05.023","article-title":"The use of trehalose-treated freeze-dried amniotic membrane for ocular surface reconstruction","volume":"29","author":"Nakamura","year":"2008","journal-title":"Biomaterials"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cryobiol.2007.10.177","article-title":"Vitrification of rabbit tissues with propylene glycol and trehalose","volume":"56","author":"Wusteman","year":"2008","journal-title":"Cryobiology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jsb.2007.01.010","article-title":"Introduction of a rod pigment aromatic cluster does not improve the structural stability of the human green cone pigment","volume":"159","author":"Giesbers","year":"2007","journal-title":"J. Struct. Boil."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.exer.2009.03.015","article-title":"Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis","volume":"89","author":"Chen","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_52","first-page":"317","article-title":"Therapeutic efficacy of trehalose eye drops for treatment of murine dry eye induced by an intelligently controlled environmental system","volume":"18","author":"Li","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.2147\/OPTH.S174290","article-title":"Trehalose\/hyaluronate eyedrop effects on ocular surface inflammatory markers and mucin expression in dry eye patients","volume":"12","author":"Fariselli","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","article-title":"TFOS DEWS II Management and Therapy Report","volume":"15","author":"Jones","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1016\/S0161-6420(02)01219-8","article-title":"Trehalose eye drops in the treatment of dry eye syndrome","volume":"109","author":"Matsuo","year":"2002","journal-title":"Ophthalmology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s10384-004-0085-8","article-title":"Trehalose Versus Hyaluronan or Cellulose in Eyedrops for the Treatment of Dry Eye","volume":"48","author":"Matsuo","year":"2004","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"595","DOI":"10.2147\/TCRM.S77091","article-title":"A randomized crossover study comparing trehalose\/hyaluronate eyedrops and standard treatment: Patient satisfaction in the treatment of dry eye syndrome","volume":"11","author":"Stolz","year":"2015","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5301\/ejo.5000836","article-title":"A Randomized, Controlled Study of the Efficacy and Safety of a New Eyedrop Formulation for Moderate to Severe Dry Eye Syndrome","volume":"27","author":"Chiambaretta","year":"2016","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1080\/03007995.2018.1434496","article-title":"Comparison of the effect of a hyaluronate\u2013trehalose solution to hyaluronate alone on Ocular Surface Disease Index in patients with moderate to severe dry eye disease","volume":"34","author":"Doan","year":"2018","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4691417-7","DOI":"10.1155\/2018\/4691417","article-title":"Effect of Hyaluronic Acid\/Trehalose in Two Different Formulations on Signs and Symptoms in Patients with Moderate to Severe Dry Eye Disease","volume":"2018","author":"Fondi","year":"2018","journal-title":"J. Ophthalmol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/aos.14252","article-title":"Disease aetiology-based design of multifunctional microemulsion eye drops for moderate or severe dry eye: A randomized, quadruple-masked and active-controlled clinical trial","volume":"98","author":"Laihia","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jtos.2019.11.004","article-title":"An artificial tear containing flaxseed oil for treating dry eye disease: A randomized controlled trial","volume":"18","author":"Downie","year":"2020","journal-title":"Ocul. Surf."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2147\/OPTH.S125203","article-title":"Effects of 3% trehalose as an adjuvant treatment after LASIK","volume":"11","author":"Mateo","year":"2017","journal-title":"Clin. Ophthalmol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.2147\/OPTH.S208256","article-title":"Efficacy of carbomer sodium hyaluronate trehalose vs hyaluronic acid to improve tear film instability and ocular surface discomfort after cataract surgery","volume":"13","author":"Caretti","year":"2019","journal-title":"Clin. Ophthalmol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1089\/jop.2019.0007","article-title":"Comparison of the Efficacy of Topical Chloramphenicol 0.5%-Betamethasone 0.2% (CB) and CB Associated with Sodium Hyaluronate\/Trehalose\/Carbomer Gel Following Strabismus Surgery","volume":"35","author":"Vagge","year":"2019","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1097\/ICO.0000000000000358","article-title":"Tear Film Thickness After Treatment With Artificial Tears in Patients With Moderate Dry Eye Disease","volume":"34","author":"Schmidl","year":"2015","journal-title":"Cornea"},{"key":"ref_67","first-page":"e307","article-title":"Effect of different lubricant eye gels on tear film thickness as measured with ultrahigh-resolution optical coherence tomography","volume":"95","author":"Wozniak","year":"2016","journal-title":"Acta Ophthalmol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Karaca, E.E., \u00d6zek, D., and Kemer, \u00d6.E. (2019). Comparison study of two different topical lubricants on tear meniscus and tear osmolarity in dry eye. Contact Lens Anterior Eye, 1.","DOI":"10.1016\/j.clae.2019.10.001"},{"key":"ref_69","unstructured":"(2020, April 02). European Patent Office Espacenet Patent Search. Available online: https:\/\/worldwide.espacenet.com."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jtos.2017.05.005","article-title":"TFOS DEWS II Introduction","volume":"15","author":"Nelson","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.clae.2013.07.004","article-title":"Bringing comfort to the masses: A novel evaluation of comfort agent solution properties","volume":"37","author":"White","year":"2014","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ejps.2008.04.006","article-title":"In vitro modulation of preservative toxicity: High molecular weight hyaluronan decreases apoptosis and oxidative stress induced by benzalkonium chloride","volume":"34","author":"Pauloin","year":"2008","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_74","first-page":"577","article-title":"High molecular weight hyaluronan decreases UVB-induced apoptosis and inflammation in human epithelial corneal cells","volume":"15","author":"Pauloin","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/em.21794","article-title":"Hyaluronic acid-dependent protection against UVB-damaged human corneal cells","volume":"54","author":"Li","year":"2013","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/8727289","article-title":"Effect of High, Medium, and Low Molecular Weight Hyaluronan on Inflammation and Oxidative Stress in an In Vitro Model of Human Nasal Epithelial Cells","volume":"2016","author":"Albano","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.carbpol.2016.07.106","article-title":"Optimization of hyaluronan-based eye drop formulations","volume":"153","author":"Salzillo","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1167\/tvst.8.6.2","article-title":"Physicochemical Properties of Hyaluronic Acid\u2013Based Lubricant Eye Drops","volume":"8","author":"Aragona","year":"2019","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/eye.1990.83","article-title":"Precorneal residence times of sodium hyaluronate solutions studied by quantitative gamma scintigraphy","volume":"4","author":"Snibson","year":"1990","journal-title":"Eye"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1136\/bjo.85.5.610","article-title":"Trehalose protects corneal epithelial cells from death by drying","volume":"85","author":"Matsuo","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"6524","DOI":"10.1002\/jcp.26583","article-title":"Autophagy induction by trehalose: Molecular mechanisms and therapeutic impacts","volume":"233","author":"Caraglia","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1111\/bph.14623","article-title":"Trehalose as a promising therapeutic candidate for the treatment of Parkinson\u2019s disease","volume":"176","author":"Khalifeh","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"615","DOI":"10.3233\/JAD-2011-101908","article-title":"Age-Related Macular Degeneration (AMD): Alzheimer\u2019s Disease in the Eye?","volume":"24","author":"Kaarniranta","year":"2011","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12944-017-0647-7","article-title":"Understanding AMD by analogy: Systematic review of lipid-related common pathogenic mechanisms in AMD, AD, AS and GN","volume":"17","author":"Xu","year":"2018","journal-title":"Lipids Heal. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1515\/pac-2016-1025","article-title":"Tailoring Trehalose for Biomedical and Biotechnological Applications","volume":"89","author":"Piligian","year":"2017","journal-title":"Pure Appl. Chem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/5\/809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:32:23Z","timestamp":1760175143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/5\/809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,25]]},"references-count":85,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["biom10050809"],"URL":"https:\/\/doi.org\/10.3390\/biom10050809","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,25]]}}}