Abstract
Purpose::
ALDH3A1 is a major corneal crystallin that is also expressed, albeit at much lower levels, in stomach, esophagus and urinary bladder of most mammalian species. The aim of this study was to elucidate the role(s) of ALDH3A1 in biological processes by examining structural and gene expression patterns in the cornea of wild type and Aldh3a1-null mice.
Methods::
Corneas from wild type and Aldh3a1(-/-) animals were examined by light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Mouse genome arrays (Affymetrix Inc) and Quantitative Real Time PCR were used to elucidate gene expression patterns in corneas of wild type and Aldh3a1-null mice.
Results::
SEM analysis revealed that the surface of wild type corneas contain more light cells than the surface of Aldh3a1(-/-) corneas, leading to speculation that there is a greater amount of apical cell turnover in the Aldh3a1-null mice than in the wild type mice. The presence of a higher number of undifferentiated corneal epithelial cells in Aldh3a1-null mice was also observed by histological analysis. Corneas from Aldh3a1-deficient mice exhibited up-regulation of chondromodulin-I and immune response, gamma-interferon-inducible gene expression. Finally, a higher frequency of H. Pylori infection was observed in the Aldh3a1-deficient mice, although this was not associated with stomach pathologies.
Conclusions::
These data are consistent with multiple functions for ALDH3A1 that include the differentiation of corneal epithelial cells and immune defense. The up-regulation of the chondromodulin-I gene suggests an anti-angiogenic function of ALDH3A1 in the avascular cornea. The diversity of roles of the abundant corneal ALDH3A1 in mice is analogous to the multifunctionality of lens crystallins, supporting its designation as a corneal crystallin.
Keywords: cornea: epithelium • gene microarray • differentiation