515
Views
5
CrossRef citations to date
0
Altmetric
REVIEW

Investigating the Ocular Surface Microbiome: What Can It Tell Us?

, , , & ORCID Icon
Pages 259-271 | Received 01 Oct 2022, Accepted 10 Jan 2023, Published online: 19 Jan 2023

References

  • Delbeke H, Younas S, Casteels I, Joossens M. Current knowledge on the human eye microbiome: a systematic review of available amplicon and metagenomic sequencing data. Acta Ophthalmol. 2021;99(1):16–25. doi:10.1111/aos.14508
  • St Leger AJ, Desai JV, Drummond RA, et al. An ocular commensal protects against corneal infection by driving an interleukin-17 response from mucosal gammadelta T cells. Immunity. 2017;47(1):148–158 e5. doi:10.1016/j.immuni.2017.06.014
  • Kugadas A, Gadjeva M. Impact of microbiome on ocular health. Ocul Surf. 2016;14(3):342–349. doi:10.1016/j.jtos.2016.04.004
  • Doan T, Akileswaran L, Andersen D, et al. Paucibacterial microbiome and resident DNA virome of the healthy conjunctiva. Invest Ophthalmol Vis Sci. 2016;57(13):5116–5126. doi:10.1167/iovs.16-19803
  • Miller D, Iovieno A. The role of microbial flora on the ocular surface. Curr Opin Allergy Clin Immunol. 2009;9(5):466–470. doi:10.1097/ACI.0b013e3283303e1b
  • Aragona P, Baudouin C, Benitez Del Castillo JM, et al. The ocular microbiome and microbiota and their effects on ocular surface pathophysiology and disorders. Surv Ophthalmol. 2021;66(6):907–925. doi:10.1016/j.survophthal.2021.03.010
  • Satokari R, Fuentes S, Mattila E, Jalanka J, de Vos WM, Arkkila P. Fecal transplantation treatment of antibiotic-induced, noninfectious colitis and long-term microbiota follow-up. Case Rep Med. 2014;2014:913867. doi:10.1155/2014/913867
  • Morgan XC, Segata N, Huttenhower C. Biodiversity and functional genomics in the human microbiome. Trends Genet. 2013;29(1):51–58. doi:10.1016/j.tig.2012.09.005
  • Joyce SA, Gahan CG. The gut microbiota and the metabolic health of the host. Curr Opin Gastroenterol. 2014;30(2):120–127. doi:10.1097/MOG.0000000000000039
  • Keilty RA. The bacterial flora of the normal conjunctiva with comparative nasal culture study. Am J Ophthalmol. 1930;13(10):876–879. doi:10.1016/S0002-9394(30)92437-3
  • Nolan J. Evaluation of conjunctival and nasal bacterial cultures before intra-ocular operations. Br J Ophthalmol. 1967;51(7):483–485. doi:10.1136/bjo.51.7.483
  • Perkins RE, Kundsin RB, Pratt MV, Abrahamsen I, Leibowitz HM. Bacteriology of normal and infected conjunctiva. J Clin Microbiol. 1975;1(2):147–149. doi:10.1128/jcm.1.2.147-149.1975
  • McNatt J, Allen SD, Wilson LA, Dowell VR. Anaerobic flora of the normal human conjunctival sac. Arch Ophthalmol. 1978;96(8):1448–1450. doi:10.1001/archopht.1978.03910060196020
  • Shovlin JP, Argüeso P, Carnt N, et al. 3. Ocular surface health with contact lens wear. Contact Lens and Anterior Eye. 2013;36:S14–S21. doi:10.1016/S1367-0484(13)60005-3
  • Knop N, Knop E. Conjunctiva-associated lymphoid tissue in the human eye. Invest Ophthalmol Vis Sci. 2000;41(6):1270–1279.
  • Siebelmann S, Gehlsen U, Huttmann G, et al. Development, alteration and real time dynamics of conjunctiva-associated lymphoid tissue. PLoS One. 2013;8(12):e82355. doi:10.1371/journal.pone.0082355
  • Pamer EG. Immune responses to commensal and environmental microbes. Nat Immunol. 2007;8(11):1173–1178. doi:10.1038/ni1526
  • Cogen AL, Nizet V, Gallo RL. Skin microbiota: a source of disease or defence? Br J Dermatol. Mar. 2008;158(3):442–455. doi:10.1111/j.1365-2133.2008.08437.x
  • Ozkan J, Willcox M, Wemheuer B, Wilcsek G, Coroneo M, Thomas T. Biogeography of the human ocular microbiota. Ocul Surf. 2019;17(1):111–118. doi:10.1016/j.jtos.2018.11.005
  • St Leger AJ, Caspi RR. Visions of Eye Commensals: the Known and the Unknown About How the Microbiome Affects Eye Disease. BioEssays. 2018;40(11):e1800046. doi:10.1002/bies.201800046
  • Lagier JC, Hugon P, Khelaifia S, Fournier PE, La Scola B, Raoult D. The rebirth of culture in microbiology through the example of culturomics to study human gut microbiota. Clin Microbiol Rev. 2015;28(1):237–264. doi:10.1128/CMR.00014-14
  • Bonnet M, Lagier JC, Raoult D, Khelaifia S. Bacterial culture through selective and non-selective conditions: the evolution of culture media in clinical microbiology. New Microbes New Infect. 2020;34:100622. doi:10.1016/j.nmni.2019.100622
  • Benn A, Heng N, Broadbent JM, Thomson WM. Studying the human oral microbiome: challenges and the evolution of solutions. Aust Dent J. 2018;63(1):14–24. doi:10.1111/adj.12565
  • Deo PN, Deshmukh R. Oral microbiome: unveiling the fundamentals. J Oral Maxillofac Pathol. 2019;23(1):122–128. doi:10.4103/jomfp.JOMFP_304_18
  • Head I, Saunders J, Pickup RW. Microbial evolution, diversity, and ecology: a decade of ribosomal RNA analysis of uncultivated microorganisms. Microb Ecol. 1998;35(1):1–21. doi:10.1007/s002489900056
  • Hahn MW, Koll U, Schmidt J. Isolation and cultivation of bacteria. In: The Structure and Function of Aquatic Microbial Communities. Springer; 2019:313–351.
  • Pham VH, Kim J. Cultivation of unculturable soil bacteria. Trends Biotechnol. 2012;30(9):475–484. doi:10.1016/j.tibtech.2012.05.007
  • Acinas SG, Sarma-Rupavtarm R, Klepac-Ceraj V, Polz MF. PCR-induced sequence artifacts and bias: insights from comparison of two 16S rRNA clone libraries constructed from the same sample. Appl Environ Microbiol. 2005;71(12):8966–8969. doi:10.1128/AEM.71.12.8966-8969.2005
  • Brooks JP, Edwards DJ, Harwich MD, et al. The truth about metagenomics: quantifying and counteracting bias in 16S rRNA studies. BMC Microbiol. 2015;15:66. doi:10.1186/s12866-015-0351-6
  • Johnson JS, Spakowicz DJ, Hong BY, et al. Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis. Nat Commun. 2019;10(1):5029. doi:10.1038/s41467-019-13036-1
  • Kennedy K, Hall MW, Lynch MD, Moreno-Hagelsieb G, Neufeld JD, Wommack KE. Evaluating bias of illumina-based bacterial 16S rRNA gene profiles. Appl Environ Microbiol. 2014;80(18):5717–5722. doi:10.1128/AEM.01451-14
  • Hornung BVH, Zwittink RD, Kuijper EJ. Issues and current standards of controls in microbiome research. FEMS Microbiol Ecol. 2019;95(5). doi:10.1093/femsec/fiz045
  • Costea PI, Zeller G, Sunagawa S, et al. Towards standards for human fecal sample processing in metagenomic studies. Nat Biotechnol. 2017;35(11):1069–1076. doi:10.1038/nbt.3960
  • Quince C, Walker AW, Simpson JT, Loman NJ, Segata N. Shotgun metagenomics, from sampling to analysis. Nat Biotechnol. 2017;35(9):833–844. doi:10.1038/nbt.3935
  • Riesenfeld CS, Schloss PD, Handelsman J. Metagenomics: genomic analysis of microbial communities. Annu Rev Genet. 2004;38:525–552. doi:10.1146/annurev.genet.38.072902.091216
  • Salter SJ, Cox MJ, Turek EM, et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 2014;12(1):1–12. doi:10.1186/s12915-014-0087-z
  • Galazzo G, van Best N, Benedikter BJ, et al. How to count our microbes? The effect of different quantitative microbiome profiling approaches. Front Cell Infect Microbiol. 2020;10:403. doi:10.3389/fcimb.2020.00403
  • Tettamanti Boshier FA, Srinivasan S, Lopez A, et al. Complementing 16S rRNA gene amplicon sequencing with total bacterial load to infer absolute species concentrations in the vaginal microbiome. mSystems. 2020;5(2). doi:10.1128/mSystems.00777-19
  • Zysset-Burri DC, Schlegel I, Lincke JB, et al. Understanding the interactions between the ocular surface microbiome and the tear proteome. Invest Ophthalmol Vis Sci. 2021;62(10):8. doi:10.1167/iovs.62.10.8
  • Lee AY, Akileswaran L, Tibbetts MD, Garg SJ, Van Gelder RN. Identification of torque teno virus in culture-negative endophthalmitis by representational deep DNA sequencing. Ophthalmology. 2015;122(3):524–530. doi:10.1016/j.ophtha.2014.09.001
  • Marotz CA, Sanders JG, Zuniga C, Zaramela LS, Knight R, Zengler K. Improving saliva shotgun metagenomics by chemical host DNA depletion. Microbiome. 2018;6(1):42. doi:10.1186/s40168-018-0426-3
  • Marquet M, Zollkau J, Pastuschek J, et al. Evaluation of microbiome enrichment and host DNA depletion in human vaginal samples using Oxford Nanopore’s adaptive sequencing. Sci Rep. 2022;12(1):4000. doi:10.1038/s41598-022-08003-8
  • Heravi FS, Zakrzewski M, Vickery K, Hu H. Host DNA depletion efficiency of microbiome DNA enrichment methods in infected tissue samples. J Microbiol Methods. 2020;170:105856. doi:10.1016/j.mimet.2020.105856
  • Shade A, Handelsman J. Beyond the Venn diagram: the hunt for a core microbiome. Environ Microbiol. 2012;14(1):4–12. doi:10.1111/j.1462-2920.2011.02585.x
  • Ta CN, Chang RT, Singh K, et al. Antibiotic resistance patterns of ocular bacterial flora. Ophthalmology. 2003;110(10):1946–1951. doi:10.1016/S0161-6420(03)00735-8
  • Graham JE, Moore JE, Jiru X, et al. Ocular pathogen or commensal: a PCR-based study of surface bacterial flora in normal and dry eyes. Invest Ophthalmol Vis Sci. 2007;48(12):5616–5623. doi:10.1167/iovs.07-0588
  • Willcox MD. Characterization of the normal microbiota of the ocular surface. Exp Eye Res. 2013;117:99–105. doi:10.1016/j.exer.2013.06.003
  • Deng Y, Wen X, Hu X, et al. Geographic difference shaped human ocular surface metagenome of young han Chinese from Beijing, Wenzhou, and Guangzhou cities. Invest Ophthalmol Vis Sci. 2020;61(2):47. doi:10.1167/iovs.61.2.47
  • Kang Y, Lin S, Ma X, et al. Strain heterogeneity, cooccurrence network, taxonomic composition and functional profile of the healthy ocular surface microbiome. Eye Vis. 2021;8(1):6. doi:10.1186/s40662-021-00228-4
  • Wen X, Miao L, Deng Y, et al. The Influence of age and sex on ocular surface microbiota in healthy adults. Invest Ophthalmol Vis Sci. 2017;58(14):6030–6037. doi:10.1167/iovs.17-22957
  • Fu Y, Wu J, Wang D, et al. Metagenomic profiling of ocular surface microbiome changes in Demodex blepharitis patients. Front Cell Infect Microbiol. 2022;12:922753. doi:10.3389/fcimb.2022.922753
  • Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol. 2018;16(3):143–155. doi:10.1038/nrmicro.2017.157
  • Andersson J, Vogt JK, Dalgaard MD, Pedersen O, Holmgaard K, Heegaard S. Ocular surface microbiota in patients with aqueous tear-deficient dry eye. Ocul Surf. 2021;19:210–217. doi:10.1016/j.jtos.2020.09.003
  • Butcher RMR, Sokana O, Jack K, et al. Active trachoma cases in the Solomon Islands have varied polymicrobial community structures but do not associate with individual non-chlamydial pathogens of the eye. Front Med. 2017;4:251. doi:10.3389/fmed.2017.00251
  • Dong X, Wang Y, Wang W, Lin P, Huang Y. Composition and diversity of bacterial community on the ocular surface of patients with meibomian gland dysfunction. Invest Ophthalmol Vis Sci. 2019;60(14):4774–4783. doi:10.1167/iovs.19-27719
  • Ham B, Hwang HB, Jung SH, Chang S, Kang KD, Kwon MJ. Distribution and diversity of ocular microbial communities in diabetic patients compared with healthy subjects. Curr Eye Res. 2018;43(3):314–324. doi:10.1080/02713683.2017.1406528
  • Huang Y, Yang B, Li W. Defining the normal core microbiome of conjunctival microbial communities. Clin Microbiol Infect. 2016;22(7):643e7–643 e12. doi:10.1016/j.cmi.2016.04.008
  • Li S, Yi G, Peng H, et al. How ocular surface microbiota debuts in type 2 diabetes mellitus. Front Cell Infect Microbiol. 2019;9:202. doi:10.3389/fcimb.2019.00202
  • Li Z, Gong Y, Chen S, et al. Comparative portrayal of ocular surface microbe with and without dry eye. J Microbiol. 2019;57(11):1025–1032. doi:10.1007/s12275-019-9127-2
  • Liang X, Li Y, Xiong K, et al. Demodex infection changes ocular surface microbial communities, in which meibomian gland dysfunction may play a role. Ophthalmol Ther. 2021;10(3):601–617. doi:10.1007/s40123-021-00356-z
  • Ozkan J, Nielsen S, Diez-Vives C, Coroneo M, Thomas T, Willcox M. Temporal stability and composition of the ocular surface microbiome. Sci Rep. 2017;7(1):9880. doi:10.1038/s41598-017-10494-9
  • Yau JW, Hou J, Tsui SKW, et al. Characterization of ocular and nasopharyngeal microbiome in allergic rhinoconjunctivitis. Pediatr Allergy Immunol. 2019;30(6):624–631. doi:10.1111/pai.13088
  • Zhang H, Zhao F, Hutchinson DS, et al. Conjunctival microbiome changes associated with soft contact lens and orthokeratology lens wearing. Invest Ophthalmol Vis Sci. 2017;58(1):128–136. doi:10.1167/iovs.16-20231
  • Zhang Z, Zou X, Xue W, Zhang P, Wang S, Zou H. Ocular surface microbiota in diabetic patients with dry eye disease. Invest Ophthalmol Vis Sci. 2021;62(12):13. doi:10.1167/iovs.62.12.13
  • Zhou Y, Holland MJ, Makalo P, et al. The conjunctival microbiome in health and trachomatous disease: a case control study. Genome Med. 2014;6(11):1–10. doi:10.1186/s13073-014-0099-x
  • Grzybowski A, Brona P, Kim SJ. Microbial flora and resistance in ophthalmology: a review. Graefes Arch Clin Exp Ophthalmol. 2017;255(5):851–862. doi:10.1007/s00417-017-3608-y
  • Smith C. Bacteriology of the healthy conjunctiva. Br J Ophthalmol. 1954;38(12):719. doi:10.1136/bjo.38.12.719
  • Suto C, Morinaga M, Yagi T, Tsuji C, Toshida H. Conjunctival sac bacterial flora isolated prior to cataract surgery. Infect Drug Resist. 2012;5:37–41. doi:10.2147/IDR.S27937
  • Capriotti JA, Pelletier JS, Shah M, Caivano DM, Ritterband DC. Normal ocular flora in healthy eyes from a rural population in Sierra Leone. Int Ophthalmol. 2009;29(2):81–84. doi:10.1007/s10792-008-9196-4
  • Honda R, Toshida H, Suto C, et al. Effect of long-term treatment with eyedrops for glaucoma on conjunctival bacterial flora. Infect Drug Resist. 2011;4:191–196. doi:10.2147/IDR.S24250
  • Cavuoto KM, Banerjee S, Miller D, Galor A. Composition and comparison of the ocular surface microbiome in infants and older children. Transl Vis Sci Technol. 2018;7(6):16. doi:10.1167/tvst.7.6.16
  • Gregorczyk M, Roskal-Wałek J. Objawy oczne w zakażeniu SARS-CoV-2 [Ocular symptoms in SARS-CoV-2 infection]. Pol Merkur Lekarski. 2022;50(296):86–93. Polish.
  • Zauli G, AlHilali S, Al-Swailem S, Secchiero P, Voltan R. Therapeutic potential of the MDM2 inhibitor Nutlin-3 in counteracting SARS-CoV-2 infection of the eye through p53 activation. Front Med. 2022;9:902713. doi:10.3389/fmed.2022.902713
  • Davis G, Li K, Thankam FG, Wilson DR, Agrawal DK. Ocular transmissibility of COVID-19: possibilities and perspectives. Mol Cell Biochem. 2022;477(3):849–864. doi:10.1007/s11010-021-04336-6
  • Verma V, Shen D, Sieving PC, Chan -C-C. The role of infectious agents in the etiology of ocular adnexal neoplasia. Surv Ophthalmol. 2008;53(4):312–331. doi:10.1016/j.survophthal.2008.04.008
  • Spurgeon ME, Lambert PF. Merkel cell polyomavirus: a newly discovered human virus with oncogenic potential. Virology. 2013;435(1):118–130. doi:10.1016/j.virol.2012.09.029
  • Kumar V, Baweja M, Singh PK, Shukla P. Recent developments in systems biology and metabolic engineering of plant–microbe interactions. Review. Front Plant Sci. 2016;7. doi:10.3389/fpls.2016.01421
  • Zárate S, Taboada B, Yocupicio-Monroy M, Arias CF. Human Virome. Arch Med Res. 2017;48(8):701–716. doi:10.1016/j.arcmed.2018.01.005
  • Shkoporov AN, Turkington CJ, Hill C. Mutualistic interplay between bacteriophages and bacteria in the human gut. Nat Rev Microbiol. 2022;20(12):737–749. doi:10.1038/s41579-022-00755-4
  • Kortright KE, Chan BK, Koff JL, Turner PE. Phage therapy: a renewed approach to combat antibiotic-resistant bacteria. Cell Host Microbe. 2019;25(2):219–232. doi:10.1016/j.chom.2019.01.014
  • Taylor VL, Fitzpatrick AD, Islam Z, Maxwell KL. The diverse impacts of phage morons on bacterial fitness and virulence. Adv Virus Res. 2019;103:1–31. doi:10.1016/bs.aivir.2018.08.001
  • Cumby N, Edwards AM, Davidson AR, Maxwell KL. The bacteriophage HK97 gp15 moron element encodes a novel superinfection exclusion protein. J Bacteriol. 2012;194(18):5012–5019. doi:10.1128/JB.00843-12
  • Smits SL, Manandhar A, van Loenen FB, et al. High prevalence of anelloviruses in vitreous fluid of children with seasonal hyperacute panuveitis. J Infect Dis. 2012;205(12):1877–1884. doi:10.1093/infdis/jis284
  • Chen T, Väisänen E, Mattila PS, Hedman K, Söderlund-Venermo M. Antigenic diversity and seroprevalences of Torque teno viruses in children and adults by ORF2-based immunoassays. J Gen Virol. 2013;94(Pt 2):409–417. doi:10.1099/vir.0.046862-0
  • Dewannieux M, Heidmann T. Endogenous retroviruses: acquisition, amplification and taming of genome invaders. Curr Opin Virol. 2013;3(6):646–656. doi:10.1016/j.coviro.2013.08.005
  • Siegal N, Gutowski M, Akileswaran L, et al. Elevated levels of Merkel cell polyoma virus in the anophthalmic conjunctiva. Sci Rep. 2021;11(1):15366. doi:10.1038/s41598-021-92642-w
  • Słowik M, Biernat MM, Urbaniak-Kujda D, Kapelko-Słowik K, Misiuk-Hojło M. Mycotic Infections of the Eye. Adv Clin Exp Med. 2015;24(6):1113–1117. doi:10.17219/acem/50572
  • Ge C, Wei C, Yang BX, Cheng J, Huang YS. Conjunctival microbiome changes associated with fungal keratitis: metagenomic analysis. Int J Ophthalmol. 2019;12(2):194–200. doi:10.18240/ijo.2019.02.02
  • Niederkorn JY. The biology of Acanthamoeba keratitis. Exp Eye Res. 2021;202:108365. doi:10.1016/j.exer.2020.108365
  • Hanson B, Zhou Y, Bautista EJ, et al. Characterization of the bacterial and fungal microbiome in indoor dust and outdoor air samples: a pilot study. Environ Sci Process Impacts. 2016;18(6):713–724. doi:10.1039/c5em00639b
  • Shivaji S, Jayasudha R, Sai Prashanthi G, Kalyana Chakravarthy S, Sharma S. The human ocular surface fungal microbiome. Invest Ophthalmol Vis Sci. 2019;60(1):451–459. doi:10.1167/iovs.18-26076
  • Wang Y, Chen H, Xia T, Huang Y. Characterization of fungal microbiota on normal ocular surface of humans. Clin Microbiol Infect. 2020;26(1):123.e9–123.e13. doi:10.1016/j.cmi.2019.05.011
  • Mitchell JI, Zuccaro A. Sequences, the environment and fungi. Mycologist. 2006;20(2):62–74. doi:10.1016/j.mycol.2005.11.004
  • Nowrousian M. Next-generation sequencing techniques for eukaryotic microorganisms: sequencing-based solutions to biological problems. Eukaryot Cell. 2010;9(9):1300–1310. doi:10.1128/ec.00123-10
  • Schoch CL, Seifert KA, Huhndorf S, et al. Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. Proce Natl Acad Sci. 2012;109(16):6241–6246. doi:10.1073/pnas.1117018109
  • Theelen B, Cafarchia C, Gaitanis G, Bassukas ID, Boekhout T, Dawson TL. Malassezia ecology, pathophysiology, and treatment. Med Mycol. 2018;56(suppl_1):S10–s25. doi:10.1093/mmy/myx134
  • Shi N, Li N, Duan X, Niu H. Interaction between the gut microbiome and mucosal immune system. Mil Med Res. 2017;4:14. doi:10.1186/s40779-017-0122-9
  • Zysset-Burri DC, Morandi S, Herzog EL, Berger LE, Zinkernagel MS. The role of the gut microbiome in eye diseases. Prog Retin Eye Res. 2022;101117. doi:10.1016/j.preteyeres.2022.101117
  • Zysset-Burri DC, Keller I, Berger LE, et al. Associations of the intestinal microbiome with the complement system in age-related macular degeneration. NPJ Genom Med. 2019;5(1):1.
  • Zinkernagel MS, Zysset-Burri DC, Keller I, et al. Association of the intestinal microbiome with the development of neovascular age-related macular degeneration. Sci Rep. 2017;7:40826. doi:10.1038/srep40826
  • Zysset-Burri DC, Keller I, Berger LE, et al. Associations of the intestinal microbiome with the complement system in neovascular age-related macular degeneration. NPJ Genom Med. 2020;5(1):1–11. doi:10.1038/s41525-020-00141-0
  • Horai R, Zárate-Bladés CR, Dillenburg-Pilla P, et al. Microbiota-dependent activation of an autoreactive T cell receptor provokes autoimmunity in an immunologically privileged site. Immunity. 2015;43(2):343–353. doi:10.1016/j.immuni.2015.07.014
  • Kugadas A, Christiansen SH, Sankaranarayanan S, et al. Impact of microbiota on resistance to ocular pseudomonas aeruginosa-induced keratitis. PLoS Pathog. 2016;12(9):e1005855. doi:10.1371/journal.ppat.1005855
  • Zhou L, Huang LQ, Beuerman RW, et al. Proteomic analysis of human tears: defensin expression after ocular surface surgery. J Proteome Res. 2004;3(3):410–416. doi:10.1021/pr034065n
  • Nakatsukasa M, Sotozono C, Shimbo K, et al. Amino Acid profiles in human tear fluids analyzed by high-performance liquid chromatography and electrospray ionization tandem mass spectrometry. Am J Ophthalmol. 2011;151(5):799–808 e1. doi:10.1016/j.ajo.2010.11.003
  • Rusciano D, Roszkowska AM, Gagliano C, Pezzino S. Free amino acids: an innovative treatment for ocular surface disease. Eur J Pharmacol. 2016;787:9–19. doi:10.1016/j.ejphar.2016.04.029
  • Liu G, Wu J, Yang H, Bao Q. Codon usage patterns in Corynebacterium glutamicum: mutational bias, natural selection and amino acid conservation. Comp Funct Genomics. 2010;2010:343569. doi:10.1155/2010/343569
  • Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449(7164):804–810. doi:10.1038/nature06244
  • Kugadas A, Wright Q, Geddes-McAlister J, Gadjeva M. Role of microbiota in strengthening ocular mucosal barrier function through secretory IgA. Invest Ophthalmol Vis Sci. 2017;58(11):4593–4600. doi:10.1167/iovs.17-22119
  • Berg G, Rybakova D, Fischer D, et al. Microbiome definition re-visited: old concepts and new challenges. Microbiome. 2020;8(1):103. doi:10.1186/s40168-020-00875-0
  • Ramirez DA, Porco TC, Lietman TM, Keenan JD. Epidemiology of conjunctivitis in US emergency departments. JAMA Ophthalmol. 2017;135(10):1119–1121. doi:10.1001/jamaophthalmol.2017.3319