{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:05:39Z","timestamp":1789787139086,"version":"4.0.1"},"reference-count":78,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:p>Dry eye and dry mouth are the principal sources of morbidity for patients with Sj\u00f6gren's syndrome (SS). There are few effective treatments, particularly systemic ones. Targeting aquaprin-5 (AQP5)-mediated tear secretion has been tested as a novel ancillary strategy and has proved promising. Patients have a great interest in using complementary medicine, including nutraceuticals and bioactive compounds to alleviate their symptoms. Potential mechanisms by which phytocompounds and bioactive compounds may benefit SS ocular and mouth symptoms through modulation of AQP5 activity are presented within this review. Supplementation with prebiotics (such as polyphenols with high bioavailability) in SS patients with lower Firmicutes\/Bacteroides (F\/B) community ratio phenotype, through administration of butyrate-producing diets, is proposed as ancillary strategy for dry eye and mouth. The potential use of natural bioactive compounds to treat dry eye could also apply to dry mouth occurring in the context of aging and SS. This novel hypothesis could have implications with respect to planning a successful dietary regimen for achieving and maintaining a normal gut microbiota in SS patients. This regimen would include augmenting butyrate-producing foodstuffs and\/or polyphenol-rich syrups, and high amounts of some specific probiotic-rich foodstuffs such as yogurt, soy yogurt, or as probiotic supplements. There are applications for pharmaceutical and nutraceutical products aiming to relieve dry eye and mouth.<\/jats:p>","DOI":"10.1089\/jop.2021.0029","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T16:01:02Z","timestamp":1627660862000},"page":"464-471","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Aquaporin5-Targeted Treatment for Dry Eye Through Bioactive Compounds and Gut Microbiota"],"prefix":"10.1177","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6221-9062","authenticated-orcid":false,"given":"Reza","family":"Rastmanesh","sequence":"first","affiliation":[{"name":"Independent Research, Private Clinic, Tehran, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,10,4]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0961203318801673"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-014-8431-1"},{"key":"e_1_3_4_4_2","volume-title":"Epiphora","author":"Patel J.","unstructured":"Patel J., , Levin A., , and Patel B.C. Epiphora. Treasure Island, FL: StatPearls Publishing; 2020."},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2011.602814"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.080846"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2012.07.005"},{"key":"e_1_3_4_8_2","author":"Kordowitzki P.","unstructured":"Kordowitzki P., , Kranc W., , Bryl R., , Kempisty B., , Skowronska A., , and Skowronski M.T. The relevance of aquaporins for the physiology, pathology, and aging of the female reproductive system in mammals. Cells. 9, 2570, 2020.","journal-title":"Cells"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1601992113"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-020-05043-6"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17550"},{"key":"e_1_3_4_12_2","first-page":"616","article-title":"Is the main lacrimal gland indispensable?","volume":"61","author":"Stevenson W.","year":"2016","unstructured":"Stevenson W., , Pugazhendhi S., , and Wang M. Is the main lacrimal gland indispensable?. Contributions of the corneal and conjunctival epithelia. Surv. Ophthalmol., 61:616\u2013627, 2016.","journal-title":"Contributions of the corneal and conjunctival epithelia. Surv. Ophthalmol."},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187188"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04140-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.2739\/kurumemedj.MS60227"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2208"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.2334\/josnusd.17-0150"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12059"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2016-308928"},{"key":"e_1_3_4_20_2","first-page":"173","article-title":"Effects of total glucosides of peony on AQP-5 and its mRNA expression in submandibular glands of NOD mice with Sjogren's syndrome","volume":"19","author":"Wu G.L.","year":"2015","unstructured":"Wu G.L., , Pu X.H., , Yu G.Y., , and Li T.Y. Effects of total glucosides of peony on AQP-5 and its mRNA expression in submandibular glands of NOD mice with Sjogren's syndrome. Eur. Rev. Med. Pharmacol. Sci. 19:173\u2013178, 2015.","journal-title":"Eur. Rev. Med. Pharmacol. Sci"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-020-3205-5"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2012.01909.x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700234"},{"key":"e_1_3_4_24_2","first-page":"1071","article-title":"Abnormal distribution of aquaporin-5 in salivary glands in the NOD mouse model for Sjogren's syndrome","volume":"32","author":"Konttinen Y.T.","year":"2005","unstructured":"Konttinen Y.T., , Tensing E.K., , Laine M., , Porola P., , Tornwall J., , and Hukkanen M. Abnormal distribution of aquaporin-5 in salivary glands in the NOD mouse model for Sjogren's syndrome. J. Rheumatol. 32:1071\u20131075, 2005.","journal-title":"J. Rheumatol"},{"key":"e_1_3_4_25_2","author":"Jeon S.","unstructured":"Jeon S., , Lee J., , Park S.H., , Kim H.D., , and Choi Y. Associations of Anti-Aquaporin 5 Autoantibodies with Serologic and Histopathological Features of Sjogren's Syndrome. J. Clin. Med. 8, 1863, 2019.","journal-title":"J. Clin. Med"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801466105"},{"key":"e_1_3_4_27_2","first-page":"8599","article-title":"The human Aquaporin-5 gene","volume":"271","author":"Lee M.D.","year":"1996","unstructured":"Lee M.D., , Bhakta K.Y., , Raina S., , Yonescu R., , Griffin C.A., , Copeland N.G., , Gilbert D.J., , Jenkins N.A., , Preston G.M., , and Agre P. The human Aquaporin-5 gene. Molecular characterization and chromosomal localization. J. Biol. Chem., 271:8599\u20138604, 1996.","journal-title":"Molecular characterization and chromosomal localization. J. Biol. Chem."},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.4.1908"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apcsb.2018.11.010"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-016-8786-x"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517717965"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.04.008"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13158"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228443"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep23561"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228733"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229029"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.2147\/JEP.S141807"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu10121989"},{"key":"e_1_3_4_40_2","author":"Lee H.Y.","unstructured":"Lee H.Y., , Gu M., , Cheng J., , Suh J.W., , and Chae H.J. Ixeris dentata and Lactobacillus gasseri extracts improve salivary secretion capability in diabetes-associated dry mouth rat model. Nutrients. 12, 1331, 2020.","journal-title":"Lactobacillus gasser"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.10.159"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2010.05.002"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2011.01456.x"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.266"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-021-00192-w"},{"key":"e_1_3_4_46_2","unstructured":"Choi Y. and Alam J. Potential role of oral microbiota and autoantibodies against either aquaporin-5 or aquaporin-1 in the pathogenesis of Sj\u00f6gren's syndrome. [Thesis]. Mountian View CA: Creative Commons 2016."},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-021-02173-7"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1446-2"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02101"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2021.1879641"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5FO00886G"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.08.028"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i40.6129"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/127.5.717"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2018.09.029"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.2174\/1871530317666170921142055"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202000473"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.06.004"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2017.1418881"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21070835"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.12.001"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.4.6.697"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.2741\/4313"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.08.006"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00120.2014"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1267\/ahc.12018"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-011-9528-4"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu9111166"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.3.42"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.12691\/jfnr-5-5-6"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1186\/1869-5760-3-4"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.200900106"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2015-000114"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11082"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12840"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2018.00238"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-64422-5"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.007"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7510174"}],"container-title":["Journal of Ocular Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/jop.2021.0029","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jop.2021.0029","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jop.2021.0029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:44:34Z","timestamp":1777646674000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/jop.2021.0029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":78,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,10,1]]}},"alternative-id":["10.1089\/jop.2021.0029"],"URL":"https:\/\/doi.org\/10.1089\/jop.2021.0029","relation":{},"ISSN":["1080-7683","1557-7732"],"issn-type":[{"value":"1080-7683","type":"print"},{"value":"1557-7732","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]}}}