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Acid proteases and histologic correlations in experimental ulceration in vitamin A deficient rabbit corneas
Abstract:
Although xerophthalmia due to severe vitamin A deficiency is the leading cause of childhood blindness in the underdeveloped countries, little is known about the proteases (other than collagenase) that are involved in the degradative mechanism. The degree of cellular autolysis and stromal degradation observed histologically in early stages of xerophthalmia and in ulcerating corneas in vitamin A deficient rabbits in this study were, in general, proportional to the levels of the proteases studied. The only major histologic and ultrastructural alteration observed in early xerophthalmic corneas was autolysis of superficial epithelial and stromal cells. In contrast, in the ulcerating corneas the stroma was infiltrated heavily with inflammatory cells and extensive stromal degradation was observed in the central necrotic region of the lesions. Maximal proteolytic activity toward hemoglobin was observed at pH 3.3 for corneal extracts from normal (N) and pair-fed control (C) rabbits and rabbits with early xerophthalmia (X) and ulcerating xerophthalmia (U) corneas. This activity was a cathepsin D-like enzyme per cornea that had a ratio of 1:1:3:16 in the N, C, X, and U corneas. The ratio of cathepsin B-like activity per cornea for N, C, X, and U corneas was 1:2:2:10.
Insights
Severe vitamin A deficiency causes xerophthalmia and childhood blindness. This study reveals increased cathepsin D and B protease activity in the corneas of vitamin A deficient rabbits, correlating with corneal degradation.
Area of Science:
- Ophthalmology
- Biochemistry
- Cell Biology
Background:
- Xerophthalmia, a leading cause of childhood blindness in developing nations, stems from severe vitamin A deficiency.
- The specific proteases involved in xerophthalmia's corneal degradation, beyond collagenase, remain largely uncharacterized.
Purpose of the Study:
- To investigate the role of specific proteases in the corneal pathology of vitamin A deficiency.
- To quantify the activity of cathepsin D-like and cathepsin B-like enzymes in normal and vitamin A deficient rabbit corneas.
Main Methods:
- Histological and ultrastructural examination of corneas from normal, pair-fed control, early xerophthalmia, and ulcerating xerophthalmia rabbits.
- Assay of proteolytic activity (cathepsin D-like and B-like) using hemoglobin as a substrate at pH 3.3.
Main Results:
- Corneal degradation and cellular autolysis were observed to be proportional to the levels of proteases studied.
- Early xerophthalmia showed autolysis of superficial epithelial and stromal cells.
- Ulcerating corneas exhibited significant stromal infiltration by inflammatory cells and extensive degradation in necrotic regions.
- Cathepsin D-like activity increased significantly (1:1:3:16 ratio for N:C:X:U corneas).
- Cathepsin B-like activity also showed a marked increase (1:2:2:10 ratio for N:C:X:U corneas).
Conclusions:
- Increased activity of cathepsin D and cathepsin B proteases contributes to corneal pathology in vitamin A deficiency.
- These enzymes play a significant role in the cellular autolysis and stromal degradation observed in xerophthalmia.