tretinoin and Wounds--Penetrating

Topical pretreatment with aIl-trans-retinoic acid (atRA) is known to improve healing of cutaneous wounds. We tested the effect of atRA on wound healing of genetically diabetic db/db mice. It is known that cutaneous wounds of db/db mice show delayed wound healing due to impaired wound contraction, delayed granulation tissue formation and underexpression of keratinocyte growth factor (KGF).. 0.1% atRA in 100 mg aqueous gel was applied to the back skin of db/db mice as well as to their normal heterozygous littermates, db/+ mice, for five consecutive days, and 2 days after completion of the atRA treatment, two round excisional wounds were created down the panniculus carnosus with a 6-mm punch biopsy on the back skin of each mouse.. After 5 days treatment with 0.1% atRA, significant hypertrophy of the epidermis and dermis, neovascularization, and inflammatory cell invasion were seen in the skin of the db/db mice, but these effects were seen only weakly in db/+ mice. Wounds in atRA-treated db/db mice closed more rapidly than those in vehicle-treated db/db mice. KGF mRNA expression, which is usually significantly lower in db/db mice than in normal mice, in wounds of atRA-treated db/db mice on day 1 of treatment was as strong as in db/+ mice.. Pretreatment with atRA reversed the impaired wound healing in db/db mice.

Topics: Administration, Topical; Animals; Diabetes Mellitus; Female; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Keratolytic Agents; Mice; Mice, Inbred C57BL; RNA, Messenger; Skin; Time Factors; Tretinoin; Wound Healing; Wounds, Penetrating

In previous studies of topical application of retinoic acid to the eye, retinoic acid in an oil vehicle has been used. An all-trans-retinoic acid (Tretinoin, USP) formulation in a petrolatum-based ophthalmic ointment vehicle has now been developed which is chemically stable for at least one year. The ointment is effective at retinoic acid concentrations of 0.01-0.1% in reversing corneal keratinization in vitamin A-deficient, xerophthalmic rabbits. At 0.1% it also stimulates the healing rate of corneal epithelial wounds in rabbits and monkeys. Retinoic acid ointment may prove to be valuable clinically in the treatment of xerophthalmia, corneal epithelial erosions, and related ocular surface abnormalities.

Topics: Animals; Corneal Injuries; Drug Stability; Epithelium; Macaca fascicularis; Ointments; Rabbits; Tretinoin; Wound Healing; Wounds, Penetrating; Xerophthalmia