Abstract
Purpose
To investigate the concentrations of transforming growth factor (TGF)-β2, matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase (TIMP)-2 in the vitreous of patients with high myopia.
Methods
Twenty-six patients with high myopia (HM) who received vitrectomy for macular retinoschisis or macular hole were enrolled in this prospective study. Twenty-six patients with idiopathic macular hole or macular epiretinal membrane were chosen as a control group. Vitreous samples were obtained during the vitrectomy surgery. The levels of TGF-β2、MMP-2、TIMP-2 in the vitreous samples were measured by enzyme-linked immunosorbent assay. The MMP activity was determined by a fluorometric assay.
Results
There was no significant difference in the vitreous level of TGF-β2 between HM (1.64 ± 0.38 ng/ml) and the control group (1.56 ± 0.32 ng/ml, p = 0.56). The vitreous levels of MMP-2 in HM (32.40 ± 14.90 ng/ml) were significantly higher than in the control group (21.42 ± 6.74 ng/ml, p < 0.01). The ratio of MMP-2/TIMP-2 was significantly elevated in the vitreous samples from HM (0.61 ± 0.19), compared to the control group (0.48 ± 0.11, p < 0.05). The MMP activity was also significantly elevated in the vitreous samples from HM (4,030.8 ± 1,257.3 FIU), compared to the control group (3,245.8 ± 835.6 FIU, p < 0.05).
Conclusions
The elevated MMP/TIMP ratio and MMP activity may play a role in the pathogenesis of human high myopia. Large prospective studies are needed to further investigate the effect of MMPs in the pathogenesis of human high myopia.
Similar content being viewed by others
References
He M, Zeng J, Liu Y et al (2004) Refractive error and visual impairment in urban children in southern china. Invest Ophthalmol Vis Sci 45:793–799
Xu L, Li Y, Wang S et al (2007) Characteristics of highly myopic eyes: the Beijing eye study. Ophthalmology 114:121–126
Qin Y, Zhu M, Qu X et al (2010) Regional macular light sensitivity changes in myopic Chinese adults: an MP1 study. Invest Ophthalmol Vis Sci 51:4451–4457
Konstantinidis L, Mantel I, Pournaras JA et al (2009) Intravitreal ranibizumab (Lucentis) for the treatment of myopic choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol 247:311–318
Li X, Wang W, Tang S et al (2009) Gas injection versus vitrectomy with gas for treating retinal detachment owing to macular hole in high myopes. Ophthalmology 116:1182–1187
Alkabes M, Padilla L, Salinas C et al (2013) Assessment of OCT measurements as prognostic factors in myopic macular hole surgery without foveoschisis. Graefes Arch Clin Exp Ophthalmol 251:2521–2527
Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor beta in human disease. N Engl J Med 342:1350–1358
Inatani M, Tanihara H, Katsuta H et al (2001) Transforming growth factor-beta 2 levels in aqueous humor of glaucomatous eyes. Graefes Arch Clin Exp Ophthalmol 239:109–113
Seko Y, Shimokawa H, Tokoro T (1995) Expression of bFGF and TGF-beta 2 in experimental myopia in chicks. Invest Ophthalmol Vis Sci 36:1183–1187
Honda S, Fujii S, Sekiya Y et al (1996) Retinal control on the axial length mediated by transforming growth factor-beta in chick eye. Invest Ophthalmol Vis Sci 37:2519–2526
Jobling AI, Nguyen M, Gentle A et al (2004) Isoform-specific changes in scleral transforming growth factor-beta expression and the regulation of collagen synthesis during myopia progression. J Biol Chem 279:18121–18126
McBrien NA (2013) Regulation of scleral metabolism in myopia and the role of transforming growth factor-beta. Exp Eye Res 114:128–140
Jobling AI, Wan R, Gentle A et al (2009) Retinal and choroidal TGF-beta in the tree shrew model of myopia: isoform expression, activation and effects on function. Exp Eye Res 88:458–466
Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8:221–233
Rönkkö S, Rekonen P, Kaarniranta K et al (2007) Matrix metalloproteinases and their inhibitors in the chamber angle of normal eyes and patients with primary open-angle glaucoma and exfoliation glaucoma. Graefes Arch Clin Exp Ophthalmol 245:697–704
Rada JA, Brenza HL (1995) Increased latent gelatinase activity in the sclera of visually deprived chicks. Invest Ophthalmol Vis Sci 36:1555–1565
Rada JA, Perry CA, Slover ML et al (1999) Gelatinase A and TIMP-2 expression in the fibrous sclera of myopic and recovering chick eyes. Invest Ophthalmol Vis Sci 40:3091–3099
Guggenheim JA, McBrien NA (1996) Form-deprivation myopia induces activation of scleral matrix metalloproteinase-2 in tree shrew. Invest Ophthalmol Vis Sci 37:1380–1395
Yang SR, Ye JJ, Long Q (2010) Expressions of collagen, matrix metalloproteases-2, and tissue inhibitor of matrix metalloproteinase-2 in the posterior sclera of newborn guinea pigs with negative lens-defocused myopia. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 32:55–59
Siegwart JT, Norton TT (2005) Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery. Invest Ophthalmol Vis Sci 46:3484–3492
Rohrer B, Stell WK (1994) Basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta) act as stop and go signals to modulate postnatal ocular growth in the chick. Exp Eye Res 58:553–561
Chen BY, Wang CY, Chen WY et al (2013) Altered TGF-β2 and bFGF expression in scleral desmocytes from an experimentally-induced myopia guinea pig model. Graefes Arch Clin Exp Ophthalmol 251:1133–1144
Kim ES, Kim MS, Moon A (2004) TGF-beta-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells. Int J Oncol 25:1375–1382
Kim ES, Sohn YW, Moon A (2007) TGF-beta-induced transcriptional activation of MMP-2 is mediated by activating transcription factor (ATF)2 in human breast epithelial cells. Cancer Lett 252:147–156
Acknowledgments
This work was supported by grants from the National Key Basic Research Program of China (2013CB967503) and the National Natural Science Foundation of China (Grant No. NSFC 81170857). The funders had no role in the design or conduct of this research.
Conflict of interest
None of the authors has any conflict of interest to disclose. The authors have no proprietary or commercial interest in any materials discussed in this article.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhuang, H., Zhang, R., Shu, Q. et al. Changes of TGF-β2, MMP-2, and TIMP-2 levels in the vitreous of patients with high myopia. Graefes Arch Clin Exp Ophthalmol 252, 1763–1767 (2014). https://doi.org/10.1007/s00417-014-2768-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-014-2768-2