Levels of cytokines in the aqueous humor of eyes with primary open angle glaucoma, pseudoexfoliation glaucoma and cataract

Authors

  • Leqaa Moemen Ophthalmology Department, Research Institute of Ophthalmology, Giza, Egypt

Keywords:

Cytokines, Primary open angle glaucoma, Pseudoexfoliation glaucoma

Abstract

Objective: The focus of this study aimed at measuring multiple inflammatory cytokines levels in the aqueous humor of patients with primary open angle glaucoma (POAG), pseudoexfoliation glaucoma (PEXG) and senile cataract. 

Methods: This case control study was conducted at the Research Institute of Ophthalmology, Giza, Egypt in 2016. Aqueous humor (AH) samples were withdrawn from 50 patients (30 POAG, and 20 PEXG) and from 15 patients with senile cataract serving as controls. The levels of IL6, IL8, transforming growth factor β1 (TGFβ1), tumor necrosis growth factor α (TNFα) and serum amyloid A (SAA) were analyzed by ELISA immune-assay. Data were analyzed by SPSS 10, using Pearson Product-Moment Correlation and independent-samples t-test.

Results: The levels of IL8, TGFβ1, TNFα and SAA were significantly higher in POAG and PEXG patients, compared to senile cataract patients. While the levels of IL6, were significantly decreased in both groups of glaucoma patients compared to cataract patients. Significant positive correlations were detected between IL6, IL 8 & TGF β1, IL 8; SAA, IL8 & TGFβ1, SAA in the aqueous humor of different groups.

Conclusion: Thus the assayed cytokines including TGFβ1, TNFα, IL8 and SAA in aqueous humor, play a vital role in IOP elevations in patients with POAG and PEXG.

References

Ritch R, Schlötzer-Schrehardt U. Exfoliation Syndrome. Surv Ophthalmol. 2001; 45(4): 265-315. doi:

1016/S0039-6257(00)00196-X

Schlötzer-Schrehardt U, Naumann GO. Ocular and Systemic Pseudoexfoliation syndrome. Am J

Ophthalmol. 2006; 141(5): 921-37. doi: 10.1016/j.ajo.2006.01.047. PMID: 16678509.

Grus FH, Joachim SC, Wuenschig D, Rieck J, Pfeiffer N. Autoimmunity and glaucoma. J Glaucoma. 2008;

(1): 79-84. doi: 10.1097/IJG.0b013e318156a592. PMID: 18303391.

Tezel G, Wax MB. The immune system and glaucoma. Curr Opin Ophthalmol. 2004; 15: 80-4. doi:

1097/00055735-200404000-00003. PMID: 15021215.

Li G, Luna C, Liton PB, Navarro I, Epstein DL, Gonzalez P. Sustained stress response after oxidative stress

in trabecular meshwork cell. Mol Vis. 2007; 13: 2282-8. PMID: 18199969, PMCID: PMC3158032.

Nakabayashi M. Review of the ischemia hypothesis for ocular hypertension other than congenital glaucoma

and closed-angle glaucoma. Ophthalmologica. 2004; 218(5): 344-9. doi: 10.1159/000079477. PMID:

Yu AL, Fuchshofer R, Kampik A, Welge-Lüssen U. Effects of oxidative stress in trabecular meshwork

cells are reduced by prostaglandin analogues. Invest Ophthalmol Vis Sci. 2008; 49(11): 4872-80. doi:

1167/iovs.07-0984. PMID: 18971427.

Zenkel M, Lewczuk P, Jünemann A, Kruse FE, Naumann GO, Schlötzer-Schrehardt U. Proinflammatory

cytokines are involved in the initiation of the abnormal matrix process in pseudoexfoliation

syndrome/glaucoma. Am J Pathol. 2010; 176(6): 2868-79. doi: 10.2353/ajpath.2010.090914. PMID:

, PMCID: PMC2877848.

Fleenor DL, Shepard AR, Hellberg PE, Jacobson N, Pang IH, Clark AF. TGFbeta2-induced changes in

human trabecular meshwork: implications for intraocular pressure. Invest Ophthalmol Vis Sci. 2006; 47(1):

-34. doi: 10.1167/iovs.05-1060. PMID: 16384967.

Kuchtey J, Rezaei KA, Jaru-Ampornpan P, Sternberg P Jr, Kuchtey RW. Multiplex cytokine analysis

reveals elevated concentration of interleukin-8 in glaucomatous aqueous humor. Invest Ophthalmol Vis

Sci. 2010; 51(12): 6441-7. doi: 10.1167/iovs.10-5216. PMID: 20592224. PMCID: PMC3055764.

Luna C, Li G, Liton PB, Qiu J, Epstein DL, Challa P, et al. Resveratrol prevents the expression of

glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol.

; 47(1): 198-204. doi: 10.1016/j.fct.2008.10.029. PMID: 19027816, PMCID: PMC2674270.

Gottanka J, Chan D, Eichhorn M, Lütjen-Drecoll E, Ethier CR. Effects of TGF-beta2 in perfused human

eyes. Invest Ophthalmol Vis Sci. 2004; 45(1): 153-8. doi: 10.1167/iovs.03-0796. PMID: 14691167.

Lütjen-Drecoll E. Morphological changes in glaucomatous eyes and the role of TGFbeta2 for the

pathogenesis of the disease. Exp Eye Res. 2005; 81(1): 1-4. doi: 10.1016/j.exer.2005.02.008. PMID:

Robertson JV, Golesic E, Gauldie J, West-Mays JA. Ocular gene transfer of active TGF-beta induces

changes in anterior segment morphology and elevated IOP in rats. Invest Ophthalmol Vis Sci. 2010; 51(1):

-18. doi: 10.1167/iovs.09-3380. PMID: 19696167.

Shifera AS, Trivedi S, Chau P, Bonnemaison LH, Iguchi R, Alvarado JA. Constitutive secretion of

chemokines by cultured human trabecular meshwork cells. Exp Eye Res. 2010; 91(1): 42-7. doi:

1016/j.exer.2010.04.001. PMID: 20403352.

Takai Y, Tanito M, Ohira A. Multiplex cytokine analysis of aqueous humor in eyes with primary open- angle glaucoma, exfoliation glaucoma, and cataract. Invest Ophthalmol Vis Sci. 2012; 53(1): 241-7. doi:

1167/iovs.11-8434. PMID: 22159018.

Wang WH, McNatt LG, Pang IH, Hellberg PE, Fingert JH, McCartney MD, et al. Increased expression of

serum amyloid A in glaucoma and its effect on intraocular pressure. Invest Ophthalmol Vis Sci. 2008;

(5): 1916-23. doi: 10.1167/iovs.07-1104. PMID: 18223246.

Eckersall PD, Bell R. Acute phase proteins: Biomarkers of infection and inflammation in veterinary

medicine. Vet J. 2010; 185(1): 23-7. doi: 10.1016/j.tvjl.2010.04.009. PMID: 20621712.

Upragarin N, Landman WJ, Gaastra W, Gruys E. Extrahepatic production of acute phase serum amyloid A.

Histol Histopathol. 2005; 20(4): 1295-307. PMID: 16136510.

Baranova IN, Vishnyakova TG, Bocharov AV, Kurlander R, Chen Z, Kimelman ML, et al. Serum amyloid

A binding to CLA-1 (CD36 and LIMPII analogous-1) mediates serum amyloid A protein-induced

activation of ERK1/2 and p38 mitogen-activated protein kinases. J Biol Chem. 2005; 280(9): 8031-40. doi:

1074/jbc.M405009200. PMID: 15576377.

Jijon HB, Madsen KL, Walker JW, Allard B, Jobin C. Serum amyloid A activates NF-kappaB and

proinflammatory gene expression in human and murine intestinal epithelial cells. Eur J Immunol. 2005;

(3): 718-26. doi: 10.1002/eji.200425688. PMID: 15724247.

Vallon R, Freuler F, Desta-Tsedu N. Serum amyloid A (apoSAA) expression is up-regulated in rheumatoid

arthritis and induces transcription of matrix metalloproteinases. J Immunol. 2001; 166(4): 2801-7. doi:

4049/jimmunol.166.4.2801. PMID: 11160347.

Furlaneto CJ, Campa A. A novel function of serum amyloid A: a potent stimulus for the release of tumor

necrosis factor-alpha, interleukin-1beta, and interleukin-8 by human blood neutrophil. Biochem Biophys

Res Commun. 2000; 268(2): 405-8. doi: 10.1006/bbrc.2000.2143. PMID: 10679217.

Liton PB, Li G, Luna C, Gonzalez P, Epstein DL. Cross-talk between TGF-beta1 and IL-6 in human

trabecular meshwork cells. Mol Vis. 2009; 15: 326-34. PMID: 19209241, PMCID: PMC2637787.

Caballero M, Liton PB, Challa P, Epstein DL, Gonzalez P. Effects of donor age on proteasome activity and

senescence in trabecular meshwork cells. Biochem Biophys Res Commun. 2004; 323(3): 1048-54. doi:

1016/j.bbrc.2004.08.195. PMID: 15381105.

Ribeiro FP, Furlaneto CJ, Hatanaka E, Ribeiro WB, Souza GM, Cassatella MA, et al. mRNA expression

and release of interleukin-8 induced by serum amyloid A in neutrophils and monocytes. Mediators

Inflamm. 2003; 12(3): 173-8. doi: 10.1080/0962935031000134897. PMID: 12857601, PMCID:

PMC1781605.

Yuan L, Neufeld AH. Tumor necrosis factor-alpha: a potentially neurodestructive cytokine produced by

glia in the human glaucomatous optic nerve head. Glia. 2000; 32(1): 42-50. doi: 10.1002/1098- 1136(200010)32:1<42::AID-GLIA40>3.0.CO;2-3.

Tezel G, Li LY, Patil RV, Wax MB. TNF-alpha and TNF-alpha receptor-1 in the retina of normal and

glaucomatous eyes. Invest Ophthalmol Vis Sci. 2001; 42(8): 1787-94. PMID: 11431443.

Sawada H, Fukuchi T, Tanaka T, Abe H. Tumor necrosis factor-alpha concentrations in the aqueous humor

of patients with glaucoma. Invest Ophthalmol Vis Sci. 2010; 51(2): 903-6. doi: 10.1167/iovs.09-4247.

PMID: 19737888.

Wang N, Chintala SK, Fini ME, Schuman JS. Activation of a tissue-specific stress response in the aqueous

outflow pathway of the eye defines the glaucoma disease phenotype. Nat Med. 2001; 7(3): 304-9. doi:

1038/85446. PMID: 11231628, PMCID: PMC1945815.

Published

2022-01-18