A mild
trauma in the form of a thermal
burn was applied to corneas of
vitamin A--deficient rats and their pair-fed controls. The control corneas routinely showed rapid re-epithelialization without stromal changes. The corneas of deficient rats recovered more slowly, frequently exhibiting stromal
edema,
leukoma, and sometimes ulceration. Because
collagenase is thought to initiate
collagen destruction in corneal ulceration, the relationships among
vitamin A status, severity of
trauma, and
collagenase levels were determine. Mild thermal
burns were found to cause corneas from less severely deficient rats to ulcerate rarely but no release increased levels of
collagenase, mainly on the first day of culture, as in the case of nonburned, severely deficient rats. Comparable
burns of corneas of pair-fed control rats resulted in no ulceration and in very little
collagenase release. Severe
burns of either pair-fed control or normal rat corneas caused ulceration and
collagenase release, but
collagenase activity was maximal on the second and third days of culture. Differences in
vitamin A status at time of burning gave rise to different patterns of
collagenase. By following the development of the
vitamin deficiency, it was determined that little active
collagenase is released after mild
burns of corneas in animals in the pre--weight plateau stage but that much more active
enzyme is released when animals are in weight plateau or 5%
weight loss stages. Studies of the effect of recovery from
vitamin A deficiency on the response to mild thermal
burn indicated that the longer the interval between feeding
vitamin A and the
burn, the lower the postburn level of
collagenase in the day 1 medium. Thus it would appear that restitution of
vitamin A status decreased the level of active
collagenase after the mild thermal
burn. The system developed here can be used to study the biochemical basis for ulceration in
vitamin A deficiency, and the possibility exists that the ulceration characteristic of
keratomalacia in people can be initiated by an environmental
trauma.