PURPOSE: To understand the underlying mechanisms responsible for the easy removal and sloughing of corneal epithelium in vitamin A deficiency. METHODS: An animal model of vitamin A deficiency, the vitamin A-deficient rat (A-rat), transmission electron microscopy, computer-assisted morphometric analysis and indirect immunofluorescence were used to study the adhesion of rat corneal epithelium to its basement membrane with emphasis on structure and molecular composition of the anchoring structures such as the hemidesmosome and bullous pemphigoid antigen. RESULTS: Transmission electron microscopy resolved numerous microseparations of the basal epithelial cell membrane from the basement membrane with intervening segmental basement membrane duplications and electron dense deposits. Morphometric analysis disclosed a statistically significant reduction in the frequency and size of hemidesmosomes. Four weeks after supplementing the diet with retinyl acetate (700 micrograms/week), significant reversal of these same structural abnormalities could be detected. Immunofluorescence staining for bullous pemphigoid antigen, a component of the adhesion complex, showed intense staining of the basal epithelial cytoplasm but weak and discontinuous staining of the basement membrane. Weak staining for laminin was also evident in A- corneas. In contrast, normal corneas displayed no cytoplasmic staining for bullous pemphigoid antigen and intense staining of the basement membrane for bullous pemphigoid antigen and laminin. CONCLUSIONS: The authors propose that structural abnormalities of the epithelial basement membrane complex are responsible for the observed loose epithelial adhesion and sloughing, as well as other known abnormalities of healing in the vitamin A-deficient rat cornea.
PURPOSE: To understand the underlying mechanisms responsible for the easy removal and sloughing of corneal epithelium in vitamin A deficiency. METHODS: An animal model of vitamin A deficiency, the vitamin A-deficient rat (A-rat), transmission electron microscopy, computer-assisted morphometric analysis and indirect immunofluorescence were used to study the adhesion of rat corneal epithelium to its basement membrane with emphasis on structure and molecular composition of the anchoring structures such as the hemidesmosome and bullous pemphigoid antigen. RESULTS: Transmission electron microscopy resolved numerous microseparations of the basal epithelial cell membrane from the basement membrane with intervening segmental basement membrane duplications and electron dense deposits. Morphometric analysis disclosed a statistically significant reduction in the frequency and size of hemidesmosomes. Four weeks after supplementing the diet with retinyl acetate (700 micrograms/week), significant reversal of these same structural abnormalities could be detected. Immunofluorescence staining for bullous pemphigoid antigen, a component of the adhesion complex, showed intense staining of the basal epithelial cytoplasm but weak and discontinuous staining of the basement membrane. Weak staining for laminin was also evident in A- corneas. In contrast, normal corneas displayed no cytoplasmic staining for bullous pemphigoid antigen and intense staining of the basement membrane for bullous pemphigoid antigen and laminin. CONCLUSIONS: The authors propose that structural abnormalities of the epithelial basement membrane complex are responsible for the observed loose epithelial adhesion and sloughing, as well as other known abnormalities of healing in the vitamin A-deficient rat cornea.