May 2005
Volume 46, Issue 13
ARVO Annual Meeting Abstract  |   May 2005
Elevated Neuregulin–1 Expression and a Distinct Pattern of Exon Usage Is Associated With Keratoconus
Author Affiliations & Notes
  • D.J. Brown
    Ophthalmology, University of California–Irvine, Irvine, CA
  • B. Holguin
    Ophthalmology, University of California–Irvine, Irvine, CA
  • E. Jhang
    Ophthalmology, University of California–Irvine, Irvine, CA
  • Footnotes
    Commercial Relationships  D.J. Brown, None; B. Holguin, None; E. Jhang, None.
  • Footnotes
    Support  Discovery Fund for Eye Research, The Skirball Program in Molecular Ophthalmology, RPB
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 4959. doi:
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      D.J. Brown, B. Holguin, E. Jhang; Elevated Neuregulin–1 Expression and a Distinct Pattern of Exon Usage Is Associated With Keratoconus . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4959.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose: The neuregulin family of growth factors plays an important role in mammalian development and regulates cell–cell interactions in a variety of organ systems in the adult. Our recent data demonstrated that multiple splice variants of neuregulin 1 (Nrg–1) are expressed in the normal adult human cornea. This study was designed to determine both the amount and form/s of Nrg–1 in keratoconus corneas. Methods: RNA was purified from isolated corneal epithelium, corneal stroma and primary cultures of both epithelial cells and stromal fibroblasts from normal and keratoconus (KC) corneas. Quantitative real time polymerase chain reactions (qPCR) were performed to determine the overall levels of Nrg–1. A combination of fluorescent primers, restriction endonucleases and image analysis were utilized to determine the proportion of each splice variant. Finally, the receptor family known to interact with Nrg–1 was examined to confirm their expression in these tissues. Results: RT–PCR and Western blot analyses demonstrate that Nrg–1 and its receptor are expressed in adult corneal tissue and cultured cells derived from this tissue. qPCR suggests that KC epithelial and stromal cells produce markedly elevated levels of Nrg–1, and that the pattern of exon usage in KC tissues is distinct and more closely resembles the pattern of exon usage seen in cultured corneal cells. Conclusions: Eight distinct forms of Nrg–1 are expressed in the adult human corneas that differ by the alternate use of four exons. This alters the predicted coding sequence in three domains of Nrg–1. These domains are known to direct ligand / receptor interaction and the trafficking, processing, and release of Nrg–1 from the cell. In KC, there is an increase in the overall amount of Nrg–1 mRNA and a preference in exon usage distinct from that found in normal corneas.

Keywords: keratoconus • cornea: basic science • gene/expression 

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