Comparative analysis of tear cytokines in patients with glaucoma, ocular hypertension, and healthy controls
Language English Country Netherlands Media print-electronic
Document type Observational Study, Journal Article
Grant support
No. 204069
Charles University Research Centre program
PubMed
37318666
PubMed Central
PMC10504217
DOI
10.1007/s10792-023-02763-6
PII: 10.1007/s10792-023-02763-6
Knihovny.cz E-resources
- Keywords
- Cytokines, Glaucoma, Inflammation, Ocular hypertension, Tears,
- MeSH
- Antihypertensive Agents therapeutic use MeSH
- Cytokines metabolism MeSH
- Glaucoma, Open-Angle * MeSH
- Glaucoma * drug therapy MeSH
- Interleukin-10 metabolism MeSH
- Interleukin-4 metabolism MeSH
- Humans MeSH
- Intraocular Pressure MeSH
- Ocular Hypertension * MeSH
- Ophthalmic Solutions MeSH
- Tears metabolism MeSH
- Case-Control Studies MeSH
- Vascular Endothelial Growth Factor A metabolism MeSH
- Inflammation metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Names of Substances
- Antihypertensive Agents MeSH
- Cytokines MeSH
- Interleukin-10 MeSH
- Interleukin-4 MeSH
- Ophthalmic Solutions MeSH
- Vascular Endothelial Growth Factor A MeSH
PURPOSE: To investigate the ocular surface inflammation in patients with primary open angle glaucoma and ocular hypertension by analyzing tears and to compare findings with healthy controls. METHODS: Observational case-control study. Tear samples were collected by 5 µl microcapillary tube from 24 patients with glaucoma treated by antiglaucoma drops, 9 non-treated patients with ocular hypertension and 45 healthy controls. Tears were analyzed from right eye by multiplex Bio-Plex system for the presence of 6 cytokines: IL1β, IL10, IL4, IFNγ, MIF and VEGF. RESULTS: Significantly higher concentrations of IL1β and IL10 (glaucoma or ocular hypertension vs. healthy controls, p < 0.0001), VEGF (glaucoma vs. ocular hypertension, p < 0.05; ocular hypertension vs. healthy controls, p < 0.02) and MIF (glaucoma vs. healthy controls, p < 0.03) were detected in patients' tears. Both patient groups have activated to a significantly lower extent the Th1 pathway represented by IFNγ than Th2 pathway represented by IL10 (p < 0.001) and, at the same time, the IFNγ/IL4 ratio was significantly increased in healthy controls (p < 0.001) and patients with ocular hypertension (p < 0.02) compared to glaucoma individuals. CONCLUSION: This study shows that secretion of inflammation-related cytokines by conjunctival cells is increased in both, glaucoma and ocular hypertension patients and can be detected in their tears. Nevertheless, data indicates stronger ocular surface inflammation in non-treated follow-up patients diagnosed with ocular hypertension than in glaucoma subjects treated by antiglaucoma drops.
See more in PubMed
Quigley H, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–267. doi: 10.1136/bjo.2005.081224. PubMed DOI PMC
Drance SM. The significance of the diurnal tension variations in normal and glaucomatous eyes. Arch Ophthalmol. 1960;64:494–501. doi: 10.1001/archopht.1960.01840010496004. PubMed DOI
Tutaj M, Brown CM, Brys M, Marthol H, Hecht MJ, Dutsch M, Michelson G, Hilz MJ. Dynamic cerebral autoregulation is impaired in glaucoma. J Neurol Sci. 2004;220:49–54. doi: 10.1016/j.jns.2004.02.002. PubMed DOI
Cooper RL, Beale DG, Constable IJ, Grose GC. Continual monitoring of intraocular pressure: effect of central venous pressure, respiration, and eye movements on continual recordings of intraocular pressure in the rabbit, dog, and man. Br J Ophthalmol. 1979;63:799–804. doi: 10.1136/bjo.63.12.799. PubMed DOI PMC
Lee AJ, Rochtchina E, Stat M, et al. Does smoking affect intraocular pressure? Findings from the blue mountains eye study. J Glaucoma. 2003;12:209–212. doi: 10.1097/00061198-200306000-00005. PubMed DOI
Chandrasekaran S, Rochtchina E, Mitchell P. Effects of caffeine on intraocular pressure the blue mountains eye study. J Glaucoma. 2005;14:504–507. doi: 10.1097/01.ijg.0000184832.08783.be. PubMed DOI
Leske MC, Heijl A, Hyman L, Bengtsson B. Early manifest glaucoma trial design and baseline data. Ophthalmology. 1999;106:2144–2153. doi: 10.1016/S0161-6420(99)90497-9. PubMed DOI
Cristina Leske M, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E. Factors for glaucoma progression and the effect of treatment the early manifest glaucoma trial. Arch Ophthalmol. 2003;121:48–56. doi: 10.1001/archopht.121.1.48. PubMed DOI
Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK, 2nd, Wilson MR, Kass MA. The ocular hypertension treatment study baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;102:714–720. doi: 10.1001/archopht.120.6.714. PubMed DOI
Gordon MO, Kass MA. The ocular hypertension treatment study design and baseline description of the participants. Arch Ophthalmol. 1999;117:573–583. doi: 10.1001/archopht.117.5.573. PubMed DOI
Cvenkel B, Kopitar AN, Ihan A. Inflammatory molecules in aqueous humour and on ocular surface and glaucoma surgery outcome. Mediat Inflamm. 2010;20:10. doi: 10.1155/2010/939602. PubMed DOI PMC
Micera A, Quaranta L, Esposito G, Floriani I, Pocobelli A, Saccà SC, Riva I, Manni G, Oddone F. Differential protein expression profiles in glaucomatous trabecular meshwork: an evaluation study on a small primary open angle glaucoma population. Adv Ther. 2016;33:252–267. doi: 10.1007/s12325-016-0285-x. PubMed DOI PMC
Yuan L, Neufeld AH. Tumor necrosis factor: a potentially neurodestructive cytokine produced by glia in the human glaucomatous optic nerve head. Glia. 2000;32:42–50. doi: 10.1002/1098-1136(200010)32:1<42::AID-GLIA40>3.0.CO;2-3. PubMed DOI
Weinstein BI, Iyer RB, Binstock JM, Hamby CV, Schwartz IS, Moy FH, Wandel T, Southren LA. Decreased 3α-hydroxysteroid dehydrogenase activity in peripheral blood lymphocytes from patients with primary open angle glaucoma. Exp Eye Res. 1996;62:39–45. doi: 10.1006/exer.1996.0005. PubMed DOI
Pieragostino D, Agnifili L, Fasanella V, D'Aguanno S, Mastropasqua R, Di Ilio C, Sacchetta P, Urbani A, Del Boccio P. Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naïve to therapy. Mol Biosyst. 2013;9:1108–1116. doi: 10.1039/c3mb25463a. PubMed DOI
Zhou L, Beuerman RW. Tear analysis in ocular surface diseases. Prog Retin Eye Res. 2012;31:527–550. doi: 10.1016/j.preteyeres.2012.06.002. PubMed DOI
Malvitte L, Montange T, Vejux A, Baudouin C, Bron AM, Creuzot-Garcher C, Lizard G. Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs. Br J Ophthalmol. 2007;91:29–32. doi: 10.1136/bjo.2006.101485. PubMed DOI PMC
Vignali DAA. Multiplexed particle-based flow cytometric assays. J Immunol Methods. 2000;243:243–255. doi: 10.1016/S0022-1759(00)00238-6. PubMed DOI
Chen X, Lei F, Zhou C, Chodosh J, Wang L, Huang Y, Dohlman CH, Paschalis EI. Glaucoma after ocular surgery or trauma: the role of infiltrating monocytes and their response to cytokine inhibitors. Am J Pathol. 2020;190:2056–2066. doi: 10.1016/j.ajpath.2020.07.006. PubMed DOI PMC
Geoffrion D, Robert MC, di Polo A, Koenekoop RK, Agoumi Y, Harissi-Dagher M. Tear film cytokine profile of patients with the boston keratoprosthesis type 1: comparing patients with and without glaucoma. Invest Ophthalmol Vis Sci. 2021 doi: 10.1167/iovs.62.4.20. PubMed DOI PMC
Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK, 2nd, Wilson MR, Gordon MO. The ocular hypertension treatment study a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701–713. doi: 10.1001/archopht.120.6.701. PubMed DOI
Markiewicz L, Pytel D, Mucha B, Szymanek K, Szaflik J, Szaflik JP, Majsterek I. Altered expression levels of MMP1, MMP9, MMP12, TIMP1, and IL-1 β as a risk factor for the elevated IOP and optic nerve head damage in the primary open-angle glaucoma patients. Biomed Res Int. 2015 doi: 10.1155/2015/812503. PubMed DOI PMC
Kokubun T, Tsuda S, Kunikata H, Asuda M, Himori N, Kunimatsu-Sanuki S, Maruyama K, Nakazawa T. Characteristic profiles of inflammatory cytokines in the aqueous humor of glaucomatous eyes. Ocul Immunol Inflamm. 2018;26:1177–1188. doi: 10.1080/09273948.2017.1327605. PubMed DOI
Kleiner G, Marcuzzi A, Zanin V, Monasta L, Zauli G. Cytokine levels in the serum of healthy subjects. Mediat Inflamm. 2013 doi: 10.1155/2013/434010. PubMed DOI PMC
Carreño E, Enríquez-De-Salamanca A, Tesón M, García-Vázquez C, Stern ME, Whitcup SM, Calonge M. Cytokine and chemokine levels in tears from healthy subjects. Acta Ophthalmol. 2010 doi: 10.1111/j.1755-3768.2010.01978.x. PubMed DOI
Burgos-Blasco B, Vidal-Villegas B, Saenz-Frances F, Morales-Fernandez L, Perucho-Gonzalez L, Garcia-Feijoo J, Martinez-de-la-Casa JM. Tear and aqueous humour cytokine profile in primary open-angle glaucoma. Acta Ophthalmol. 2020;98:e768–e772. doi: 10.1111/aos.14374. PubMed DOI
Chua J, Vania M, Ming Gemmy Cheung C, Ang M, Chee SP, Yang H, Li J, Wong TT. Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes. Mol Vis. 2012;18:431–438. PubMed PMC
Pisella PJ, Debbasch C, Hamard P, Creuzot-Garcher C, Rat P, Brignole F, Baudouin C. Conjunctival proinflammatory and proapoptic effects of latanoprost and preserved and unpreserved timolol: an ex vivo and in vivo study. Invest Ophthalmol Vis Sci. 2004;45:1360–1368. doi: 10.1167/iovs.03-1067. PubMed DOI
Baudouin C, Hamard P, Liang H, Creuzot-Garcher C, Bensoussan L, Brignole F. Conjunctival epithelial cell expression of interleukins and inflammatory markers in glaucoma patients treated over the long term. Ophthalmology. 2004;111:2186–2192. doi: 10.1016/j.ophtha.2004.06.023. PubMed DOI
Manni G, Centofanti M, Oddone F, Parravano M, Bucci MG. Interleukin-1β tear concentration in glaucomatous and ocular hypertensive patients treated with preservative-free nonselective beta-blockers. Am J Ophthalmol. 2005;139:72–77. doi: 10.1016/j.ajo.2004.08.028. PubMed DOI
Martinez-de-la-Casa JM, Perez-Bartolome F, Urcelay E, Santiago JL, Moreno-Montañes J, Arriola-Villalobos P, Benitez-Del-Castillo JM, Garcia-Feijoo J. Tear cytokine profile of glaucoma patients treated with preservative-free or preserved latanoprost. Ocular Surface. 2017;15:723–729. doi: 10.1016/j.jtos.2017.03.004. PubMed DOI
Furtado JM, Silva J, Ii P, Dhegaide NH, Rocha EM, Donadi E, Rodrigues Mde L. Conjunctival inflammation in patients under topical glaucoma treatment with indication to surgery. Acta Cir Bras. 2012;27:732–735. doi: 10.1590/S0102-86502012001000011. PubMed DOI
Ahmed F, Brown KM, Stephan DA, Morrison JC, Johnson EC, Tomarev SI. Microarray analysis of changes in mRNA levels in the rat retina after experimental elevation of intraocular pressure. Invest Ophthalmol Vis Sci. 2004;45:1247–1258. doi: 10.1167/iovs.03-1123. PubMed DOI