Skip to main content

Advertisement

SpringerLink
Log in

Increased expression of periostin and tenascin-C in eyes with neovascular glaucoma secondary to PDR

  • Glaucoma
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To investigate periostin (PN) and tenascin-C (TNC) expression in the aqueous humor and trabeculectomy specimens of patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy (PDR).

Methods

This study enrolled 37 eyes of 37 patients who were grouped into (1) NVG secondary to PDR (NVG; n = 8); (2) PDR without NVG (PDR; n = 9); (3) primary open-angle glaucoma (POAG; n = 11); and (4) cataract surgery patients as a control group (CG; n = 9). Aqueous humor samples were collected from the anterior chamber at the start of surgery or intravitreal injection of anti-VEGF drug. The concentrations of PN, TNC, VEGF, and TGF-β2 (transforming growth factor-beta 2) were measured by ELISA. Sclerostomy tissues containing trabecular meshwork were obtained from two NVG patients and a POAG patient who underwent trabeculectomy surgery. Immunohistochemical analyses were performed to determine the localization of PN and TNC expression in the sclerostomy tissues.

Results

PN and TNC-C levels were below detection threshold in the POAG and CG groups. The NVG group had significantly higher levels of PN and TNC compared with the PDR group (84.7 ng/ml vs 2.2 ng/ml and 18.5 ng/ml vs 4.6 ng/ml, respectively; p < 0.05). There was a significant correlation between the levels of PN and TNC-C in the NVG group (r = 0.86, p < 0.05). We found significant expression of PN in the trabecular meshwork and Schlemm’s canal of sclerostomy tissues excised from patients with NVG.

Conclusions

Increased PN and TNC expression suggests their possible involvement in the pathogenesis of NVG secondary to PDR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Havens SJ, Gulati V (2016) Neovascular glaucoma. Dev Ophthalmol 55:196–204

    Article  Google Scholar 

  2. Shazly TA, Latina MA (2009) Neovascular glaucoma: etiology, diagnosis and prognosis. Semin Ophthalmol 24(2):113–121

    Article  Google Scholar 

  3. Kohno R, Hata Y, Mochizuki Y, Arita R, Kawahara S, Kita T, Miyazaki M, Hisatomi T, Ikeda Y, Aiello LP, Ishibashi T (2010) Histopathology of neovascular tissue from eyes with proliferative diabetic retinopathy after intravitreal bevacizumab injection. Am J Ophthalmol 150(2):223–229 e221

    Article  CAS  Google Scholar 

  4. John T, Sassani JW, Eagle RC Jr (1983) The myofibroblastic component of rubeosis iridis. Ophthalmology 90(6):721–728

    Article  CAS  Google Scholar 

  5. Miao H, Hou X, Hwang DK, Tao Y (2018) Vascular endothelial growth factor, basic fibroblast growth factor, and pigment epithelium-derived factor expression in the neovascular iris in retinal diseases. J Ophthalmol 2018:8025951

    PubMed  PubMed Central  Google Scholar 

  6. Yu XB, Sun XH, Dahan E, Guo WY, Qian SH, Meng FR, Song YL, Simon GJ (2007) Increased levels of transforming growth factor-betal and -beta2 in the aqueous humor of patients with neovascular glaucoma. Ophthalmic Surg Lasers Imaging 38(1):6–14

    Article  Google Scholar 

  7. Tripathi RC, Li J, Tripathi BJ, Chalam KV, Adamis AP (1998) Increased level of vascular endothelial growth factor in aqueous humor of patients with neovascular glaucoma. Ophthalmology 105(2):232–237

    Article  CAS  Google Scholar 

  8. Sone H, Okuda Y, Kawakami Y, Hanatani M, Suzuki H, Kozawa T, Honmura S, Yamashita K (1996) Vascular endothelial growth factor level in aqueous humor of diabetic patients with rubeotic glaucoma is markedly elevated. Diabetes Care 19(11):1306–1307

    Article  CAS  Google Scholar 

  9. Ohira S, Inoue T, Shobayashi K, Iwao K, Fukushima M, Tanihara H (2015) Simultaneous increase in multiple proinflammatory cytokines in the aqueous humor in neovascular glaucoma with and without intravitreal bevacizumab injection. Invest Ophthalmol Vis Sci 56(6):3541–3548

    Article  CAS  Google Scholar 

  10. Ishikawa K, Yoshida S, Kobayashi Y, Zhou Y, Nakama T, Nakao S, Sassa Y, Oshima Y, Niiro H, Akashi K, Kono T, Ishibashi T (2015) Microarray analysis of gene expression in fibrovascular membranes excised from patients with proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 56(2):932–946

    Article  CAS  Google Scholar 

  11. Nakama T, Yoshida S, Ishikawa K, Kubo Y, Kobayashi Y, Zhou Y, Nakao S, Hisatomi T, Ikeda Y, Takao K, Yoshikawa K, Matsuda A, Ono J, Ohta S, Izuhara K, Kudo A, Sonoda KH, Ishibashi T (2017) Therapeutic effect of novel single-stranded RNAi agent targeting periostin in eyes with retinal neovascularization. Mol Ther Nucleic Acids 6:279–289

    Article  CAS  Google Scholar 

  12. Kobayashi Y, Yoshida S, Zhou Y, Nakama T, Ishikawa K, Arima M, Nakao S, Sassa Y, Takeda A, Hisatomi T, Ikeda Y, Matsuda A, Sonoda KH, Ishibashi T (2016) Tenascin-C promotes angiogenesis in fibrovascular membranes in eyes with proliferative diabetic retinopathy. Mol Vis 22:436–445

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Ishikawa K, Yoshida S, Nakao S, Nakama T, Kita T, Asato R, Sassa Y, Arita R, Miyazaki M, Enaida H, Oshima Y, Murakami N, Niiro H, Ono J, Matsuda A, Goto Y, Akashi K, Izuhara K, Kudo A, Kono T, Hafezi-Moghadam A, Ishibashi T (2014) Periostin promotes the generation of fibrous membranes in proliferative vitreoretinopathy. FASEB J 28(1):131–142

    Article  CAS  Google Scholar 

  14. Yoshida S, Ishikawa K, Asato R, Arima M, Sassa Y, Yoshida A, Yoshikawa H, Narukawa K, Obika S, Ono J, Ohta S, Izuhara K, Kono T, Ishibashi T (2011) Increased expression of periostin in vitreous and fibrovascular membranes obtained from patients with proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 52(8):5670–5678

    Article  CAS  Google Scholar 

  15. Kobayashi Y, Yoshida S, Zhou Y, Nakama T, Ishikawa K, Kubo Y, Arima M, Nakao S, Hisatomi T, Ikeda Y, Matsuda A, Sonoda KH, Ishibashi T (2016) Tenascin-C secreted by transdifferentiated retinal pigment epithelial cells promotes choroidal neovascularization via integrin alphaV. Lab Investig 96(11):1178–1188

    Article  CAS  Google Scholar 

  16. Kita T, Hata Y, Kano K, Miura M, Nakao S, Noda Y, Shimokawa H, Ishibashi T (2007) Transforming growth factor-beta2 and connective tissue growth factor in proliferative vitreoretinal diseases: possible involvement of hyalocytes and therapeutic potential of Rho kinase inhibitor. Diabetes 56(1):231–238

    Article  CAS  Google Scholar 

  17. Min SH, Lee TI, Chung YS, Kim HK (2006) Transforming growth factor-beta levels in human aqueous humor of glaucomatous, diabetic and uveitic eyes. Korean J Ophthalmol 20(3):162–165

    Article  Google Scholar 

  18. Nakama T, Yoshida S, Ishikawa K, Kobayashi Y, Zhou Y, Nakao S, Sassa Y, Oshima Y, Takao K, Shimahara A, Yoshikawa K, Hamasaki T, Ohgi T, Hayashi H, Matsuda A, Kudo A, Nozaki M, Ogura Y, Kuroda M, Ishibashi T (2015) Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin. Gene Ther 22(2):127–137

    Article  CAS  Google Scholar 

  19. Kudo A, Kii I (2018) Periostin function in communication with extracellular matrices. J Cell Commun Signal 12(1):301–308

    Article  Google Scholar 

  20. Kii I, Nishiyama T, Li M, Matsumoto K, Saito M, Amizuka N, Kudo A (2010) Incorporation of tenascin-C into the extracellular matrix by periostin underlies an extracellular meshwork architecture. J Biol Chem 285(3):2028–2039

    Article  CAS  Google Scholar 

  21. Takayama G, Arima K, Kanaji T, Toda S, Tanaka H, Shoji S, McKenzie AN, Nagai H, Hotokebuchi T, Izuhara K (2006) Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J Allergy Clin Immunol 118(1):98–104

    Article  CAS  Google Scholar 

  22. Stamer WD, Clark AF (2017) The many faces of the trabecular meshwork cell. Exp Eye Res 158:112–123

    Article  CAS  Google Scholar 

  23. Keller KE, Aga M, Bradley JM, Kelley MJ, Acott TS (2009) Extracellular matrix turnover and outflow resistance. Exp Eye Res 88(4):676–682

    Article  CAS  Google Scholar 

  24. Norris RA, Potts JD, Yost MJ, Junor L, Brooks T, Tan H, Hoffman S, Hart MM, Kern MJ, Damon B, Markwald RR, Goodwin RL (2009) Periostin promotes a fibroblastic lineage pathway in atrioventricular valve progenitor cells. Dev Dyn 238(5):1052–1063

    Article  CAS  Google Scholar 

  25. Horiuchi K, Amizuka N, Takeshita S, Takamatsu H, Katsuura M, Ozawa H, Toyama Y, Bonewald LF, Kudo A (1999) Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta. J Bone Miner Res 14(7):1239–1249

    Article  CAS  Google Scholar 

  26. Chono I, Miyazaki D, Miyake H, Komatsu N, Ehara F, Nagase D, Kawamoto Y, Shimizu Y, Ideta R, Inoue Y (2018) High interleukin-8 level in aqueous humor is associated with poor prognosis in eyes with open angle glaucoma and neovascular glaucoma. Sci Rep 8(1):14533

    Article  Google Scholar 

  27. SooHoo JR, Seibold LK, Pantcheva MB, Kahook MY (2015) Aflibercept for the treatment of neovascular glaucoma. Clin Exp Ophthalmol 43(9):803–807

    Article  Google Scholar 

Download references

Funding

This study was funded by the Japan Society for the Promotion of Science (KAKENHI grants 17H05101 and 18K09450).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan

    Keijiro Ishikawa, Ri-ichiro Kohno, Kenichiro Mori, Yusuke Murakami, Shintaro Nakao, Masato Akiyama & Koh-Hei Sonoda

  2. Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan

    Shigeo Yoshida

Authors
  1. Keijiro Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ri-ichiro Kohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenichiro Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yusuke Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shintaro Nakao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masato Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shigeo Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Koh-Hei Sonoda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keijiro Ishikawa.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of the Kyushu University Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ishikawa, K., Kohno, Ri., Mori, K. et al. Increased expression of periostin and tenascin-C in eyes with neovascular glaucoma secondary to PDR. Graefes Arch Clin Exp Ophthalmol 258, 621–628 (2020). https://doi.org/10.1007/s00417-019-04574-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-019-04574-x

Keywords

Search

Navigation