Article Text

Expression of transforming growth factor β superfamily and their receptors in the corneal stromal wound healing process after excimer laser keratectomy
  1. YUICHI KAJI
  1. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  2. Second Department of Ophthalmology, University of Toho School of Medicine, Tokyo, Japan
  3. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  4. Department of Ophthalmology, Unversity of California School of Medicine, San Fransisco, USA
  5. Santen Pharmaceutical Co, Ltd, Nara Reserch and Developmental Center, Nara, Japan
  6. Department of Biochemistry, the Cancer Institute, Tokyo, Japan
  7. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  1. TOMONAO MITA
  1. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  2. Second Department of Ophthalmology, University of Toho School of Medicine, Tokyo, Japan
  3. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  4. Department of Ophthalmology, Unversity of California School of Medicine, San Fransisco, USA
  5. Santen Pharmaceutical Co, Ltd, Nara Reserch and Developmental Center, Nara, Japan
  6. Department of Biochemistry, the Cancer Institute, Tokyo, Japan
  7. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  1. HIROTO OBATA,
  2. TADAHIKO TSURU
  1. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  2. Second Department of Ophthalmology, University of Toho School of Medicine, Tokyo, Japan
  3. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  4. Department of Ophthalmology, Unversity of California School of Medicine, San Fransisco, USA
  5. Santen Pharmaceutical Co, Ltd, Nara Reserch and Developmental Center, Nara, Japan
  6. Department of Biochemistry, the Cancer Institute, Tokyo, Japan
  7. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  1. KOUICHI SOYA
  1. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  2. Second Department of Ophthalmology, University of Toho School of Medicine, Tokyo, Japan
  3. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  4. Department of Ophthalmology, Unversity of California School of Medicine, San Fransisco, USA
  5. Santen Pharmaceutical Co, Ltd, Nara Reserch and Developmental Center, Nara, Japan
  6. Department of Biochemistry, the Cancer Institute, Tokyo, Japan
  7. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  1. EIICHI SHIRASAWA,
  2. HIROYUKI SAKAI
  1. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  2. Second Department of Ophthalmology, University of Toho School of Medicine, Tokyo, Japan
  3. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  4. Department of Ophthalmology, Unversity of California School of Medicine, San Fransisco, USA
  5. Santen Pharmaceutical Co, Ltd, Nara Reserch and Developmental Center, Nara, Japan
  6. Department of Biochemistry, the Cancer Institute, Tokyo, Japan
  7. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  1. AKI HANYU,
  2. MITSUYASU KATO
  1. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  2. Second Department of Ophthalmology, University of Toho School of Medicine, Tokyo, Japan
  3. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  4. Department of Ophthalmology, Unversity of California School of Medicine, San Fransisco, USA
  5. Santen Pharmaceutical Co, Ltd, Nara Reserch and Developmental Center, Nara, Japan
  6. Department of Biochemistry, the Cancer Institute, Tokyo, Japan
  7. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  1. HIDETOSHI YAMASHITA
  1. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  2. Second Department of Ophthalmology, University of Toho School of Medicine, Tokyo, Japan
  3. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  4. Department of Ophthalmology, Unversity of California School of Medicine, San Fransisco, USA
  5. Santen Pharmaceutical Co, Ltd, Nara Reserch and Developmental Center, Nara, Japan
  6. Department of Biochemistry, the Cancer Institute, Tokyo, Japan
  7. Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  1. Yuichi Kaji, MD, Department of Ophthalmology, University of Tokyo School of Medicine, Hongou 7-3-1, Bunkyo-ku, Tokyo, 113-8655 Japan.

Statistics from Altmetric.com

Editor,—Corneal stromal clouding (corneal haze) develops after excimer laser keratectomy. During the corneal wound healing process after excimer laser keratectomy, abnormal subepithelial fibrous tissue is formed just under the abraded area, where keratocytes proliferate and extracellular matrix (ECM) components, including collagens (type III, IV, and VII), fibronectin, laminin, and tenascin, are deposited.1-3 This abnormal ECM deposition is thought to correspond to the corneal haze.

The transforming growth factor β (TGF-β) superfamily contains many multifunctional proteins, including TGF-βs, activins, and bone morphogenetic proteins (BMPs).4 They regulate cellular proliferation, differentiation, migration, and ECM production.4 Through these functions, TGF-β is known to regulate the wound healing process in many tissue. For example, TGF-β accelerates the abnormal ECM deposition and scar tissue formation in the skin wound healing process in vivo.5 TGF-β also accelerates the proliferation and ECM production of the cultured skin fibroblasts in vitro.6 In the corneal cells, TGF-β and TGF-β receptors are expressed in resting status and in the wound healing process after injury.7 TGF-β is reported to stimulate ECM production of keratocytes. These facts suggest that TGF-β is involved in corneal haze formation. In the present report, we tried to investigate the role of the TGF-β superfamily on the corneal stromal wound healing process and the corneal haze formation after excimer laser keratectomy.

CASE REPORT

The central areas measuring 6 mm in diameter of 20 corneas of European cats were abraded to 100 μm depth using an EC 5000 excimer laser (Nidek, Aichi, Japan). After excimer laser keratectomy, corneal haze was quantitated using a newly developed device (EAS-1000, Nidek, Aichi, Japan) that measures scattered light intensity of the cornea.8 In parallel with the haze measurement, the expressions of TGF-βs, TGF-β type I and II receptors, activin type I, IB, and II receptors, BMP type IA, IB, and type II receptors, collagens (type I, III, and IV), fibronectin, and laminin were immunohistochemically observed in the cryosections of the corneas without treatment and 3 days, 1 week, 4 weeks, and 10 weeks after excimer laser keratectomy.

COMMENT

Table 1 shows the intensity of the corneal haze and the expression of the TGF-βs, TGF-β superfamily receptors, and ECM components in the corneas before and after excimer laser keratectomy. The corneal haze gradually increased and reached the peak 4 weeks after treatment. In the subepithelial tissue of the laser irradiated area, the keratocyte proliferation and expression increase of type III and type IV collagens, fibronectin, and laminin were observed. Among the TGF-β family and the TGF-β superfamily receptors, only the TGF-β1, β2, β3 (Fig 1), and TGF-β type I and type II receptors were significantly upregulated in the activated keratocytes under the regenerating epithelium 4 weeks after the treatment The expression of activin receptors and BMP receptors were only slightly increased. The synchronised increase in the expression of TGF-βs, TGF-β receptors, the abnormal extracellular matrix deposition, and corneal haze formation suggests that TGF-β is involved in the activation of keratocyte function during the corneal stromal wound healing process and could affect corneal haze formation after excimer laser keratectomy.

Table 1

The intensity of corneal haze, and expression of extracellular matrix components, TGF-βs, and TGF-β superfamily receptors

Figure 1

(A) Expression of TGF-β3 without treatment. TGF-β3 is detected in the corneal epithelial cells. Expression of TGF-β3 in keratocytes is very weak. (B) 4 weeks after the excimer laser keratectomy. The expression of TGF-β3 increases in the keratocytes which proliferate in the subepithelium of the laser irradiated area. Expression of TGF-β3 does not change in corneal epithelial cells (bar = 100 μm).

References

View Abstract

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.