This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jester, J. V. Articles by Herman, I. M. Search for Related Content PubMed PubMed Citation Articles by Jester, J. V. Articles by Herman, I. M.

American Journal of Pathology, Vol 127, 140-148, Copyright © 1987 by American Society for Investigative Pathology

REGULAR ARTICLES

Characterization of avascular corneal wound healing fibroblasts. New insights into the myofibroblast

JV Jester, MM Rodrigues and IM Herman

The characteristics and derivation of corneal wound healing fibroblasts (myofibroblasts) were evaluated by studying the temporal changes in the cellular actin distribution of corneal fibrocytes following full thickness 3-mm diameter central corneal wounds in the rabbit. Under certain conditions these wounds heal without neovascularization, allowing for the detailed analysis of invading fibroblasts with minimal contamination by other cell types. The authors employed transmission electron microscopy to localize microfilaments, fluorescent microscopy using NBD-phallacidin, a mushroom toxin which binds specifically to f- actin and oligomeres of g-actin, to localize actin filaments, and isoelectric focusing gels to characterize actin isotypes. During the early stages of wound healing (1-7 days) there is a gradual change in the corneal fibrocytes adjacent to the wound margin characterized by the development of extensive rough endoplasmic reticulum, microtubules, a prominent Golgi apparatus, and a cortical microfilament network. This is in contrast to the normal fibrocyte, which, for the most part, lacks these structures. The development of microfilaments correlated with increased NBD-phallacidin fluorescence of fibrocytes adjacent to the wound as compared with fibrocytes farther removed from the site of injury. Fibroblasts appearing within the wound from 7 days to 2 months after injury had ultrastructural characteristics similar to those of myofibroblasts, including parallel arrays of microfilaments, stress fibers and cell-cell, cell-matrix attachments. Furthermore, these cells stained intensely with NBD-phallacidin, supporting the ultrastructural findings. At 1 month after injury, cells contained within the wound possessed predominantly nonmuscle isoactins (gamma) as seen by silver staining of isoelectric focusing gels, but little or no (smooth muscle) isoactins could be detected. Moreover, no significant differences could be detected between electrophoretic profiles obtained from wounded versus normal corneas. These morphologic and biochemical data suggest that the corneal fibrocyte may develop into a fibroblastlike cell similar to the myofibroblast, and is characterized by a marked increase in filamentous actin.

This article has been cited by other articles:

				G Perrella, P Brusini, R Spelat, P Hossain, A Hopkinson, and H S Dua Expression of haematopoietic stem cell markers, CD133 and CD34 on human corneal keratocytes Br J Ophthalmol, January 1, 2007; 91(1): 94 - 99. [Abstract] [Full Text] [PDF]

				H. Karring, I. B. Thogersen, G. K. Klintworth, J. J. Enghild, and T. Moller-Pedersen Proteomic Analysis of the Soluble Fraction from Human Corneal Fibroblasts with Reference to Ocular Transparency Mol. Cell. Proteomics, July 1, 2004; 3(7): 660 - 674. [Abstract] [Full Text] [PDF]

				Q. Garrett, P. T. Khaw, T. D. Blalock, G. S. Schultz, G. R. Grotendorst, and J. T. Daniels Involvement of CTGF in TGF-{beta}1-Stimulation of Myofibroblast Differentiation and Collagen Matrix Contraction in the Presence of Mechanical Stress Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1109 - 1116. [Abstract] [Full Text] [PDF]

				J. L. Funderburgh, M. M. Mann, and M. L. Funderburgh Keratocyte Phenotype Mediates Proteoglycan Structure: A ROLE FOR FIBROBLASTS IN CORNEAL FIBROSIS J. Biol. Chem., November 14, 2003; 278(46): 45629 - 45637. [Abstract] [Full Text] [PDF]

				M. Vishwanath, L. Ma, C. A. Otey, J. V. Jester, and W. M. Petroll Modulation of Corneal Fibroblast Contractility within Fibrillar Collagen Matrices Invest. Ophthalmol. Vis. Sci., November 1, 2003; 44(11): 4724 - 4735. [Abstract] [Full Text] [PDF]

				K. Nakamura, D. Kurosaka, M. Yoshino, T. Oshima, and H. Kurosaka Injured Corneal Epithelial Cells Promote Myodifferentiation of Corneal Fibroblasts Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2603 - 2608. [Abstract] [Full Text] [PDF]

				K. Ohno, K. Mitooka, L. R. Nelson, D. O. Hodge, and W. M. Bourne Keratocyte Activation and Apoptosis in Transplanted Human Corneas in a Xenograft Model Invest. Ophthalmol. Vis. Sci., April 1, 2002; 43(4): 1025 - 1031. [Abstract] [Full Text] [PDF]

				L. You and F. E. Kruse Differential Effect of Activin A and BMP-7 on Myofibroblast Differentiation and the Role of the Smad Signaling Pathway Invest. Ophthalmol. Vis. Sci., January 1, 2002; 43(1): 72 - 81. [Abstract] [Full Text] [PDF]

				Y. Morishima, A. Nomura, Y. Uchida, Y. Noguchi, T. Sakamoto, Y. Ishii, Y. Goto, K. Masuyama, M. J. Zhang, K. Hirano, et al. Triggering the Induction of Myofibroblast and Fibrogenesis by Airway Epithelial Shedding Am. J. Respir. Cell Mol. Biol., January 1, 2001; 24(1): 1 - 11. [Abstract] [Full Text]

				J. V. Jester, J. Huang, P. A. Barry-Lane, W. W-Y. Kao, W. M. Petroll, and H. D. Cavanagh Transforming Growth Factor{beta}-Mediated Corneal Myofibroblast Differentiation Requires Actin and Fibronectin Assembly Invest. Ophthalmol. Vis. Sci., August 1, 1999; 40(9): 1959 - 1967. [Abstract] [Full Text] [PDF]

				G. R. J. Melles, P. S. Binder, M. N. Moore, and J. A. Anderson Epithelial-Stromal Interactions in Human Keratotomy Wound Healing Arch Ophthalmol, September 1, 1995; 113(9): 1124 - 1130. [Abstract] [PDF]

				G. R. J. Melles, P. S. Binder, and J. A. Anderson Variation in Healing Throughout the Depth of Long-term, Unsutured, Corneal Wounds in Human Autopsy Specimens and Monkeys Arch Ophthalmol, January 1, 1994; 112(1): 100 - 109. [Abstract] [PDF]

				W. Petroll, H. Cavanagh, P Barry, P Andrews, and J. Jester Quantitative analysis of stress fiber orientation during corneal wound contraction J. Cell Sci., January 2, 1993; 104(2): 353 - 363. [Abstract] [PDF]

				B. V. Chetty, R. E. Boissy, G. D. Warden, and J. J. Nordlund Basement Membrane and Fibroblast Aberration in Blisters at the Donor, Graft, and Spontaneously Healed Sites in Patients With Burns Arch Dermatol, February 1, 1992; 128(2): 181 - 186. [Abstract] [PDF]