tretinoin and Corneal-Ulcer

Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Aged; Animals; Child; Cholera Toxin; Colchicine; Cornea; Corneal Ulcer; Cyanoacrylates; Epithelium; Eye Burns; Female; Fibronectins; Flurbiprofen; Guinea Pigs; Humans; Immunosuppressive Agents; Male; Middle Aged; Rabbits; Rats; Retinoids; Tears; Tissue Adhesives; Tretinoin

Alkali burns are the most common, severe chemical ocular injuries, their functional prognosis depending on corneal wound healing efficiency. The purpose of our study was to compare the benefits of amniotic membrane (AM) grafts and homogenates for wound healing in the presence or absence of previous all-trans retinoic acid (atRA) treatment.. Fifty male CD1 mice with reproducible corneal chemical burn were divided into five groups, as follows: group 1 was treated with saline solution; groups 2 and 3 received untreated AM grafts or grafts treated with atRA, respectively; and groups 4 and 5 received untreated AM homogenates or homogenates treated with atRA, respectively. After 7 days of treatment, ulcer area and depth were measured, and vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were quantified.. AM induction by atRA was confirmed via quantification of retinoic acid receptor β (RARβ), a well-established retinoic acid-induced gene. Significant improvements of corneal wound healing in terms of ulcer area and depth were obtained with both strategies. No major differences were found between the efficiency of AM homogenates and grafts. This positive action was increased when AM was pretreated with atRA. Furthermore, AM induced a decrease in VEGF and MMP-9 levels during the wound healing process. The atRA treatment led to an even greater decrease in the expression of both proteins.. Amnion homogenate is as effective as AM grafts in promoting corneal wound healing in a mouse model. A higher positive effect was obtained with atRA treatment.

Topics: Alkalies; Amnion; Animals; Burns, Chemical; Corneal Ulcer; Disease Models, Animal; Eye Burns; Fluorescent Antibody Technique, Indirect; Humans; Keratolytic Agents; Male; Matrix Metalloproteinase 9; Mice; Tissue Engineering; Transplants; Tretinoin; Vascular Endothelial Growth Factor A; Wound Healing

We examined the effect of all-trans retinoic acid on collagen degradation mediated by corneal fibroblasts.. Rabbit corneal fibroblasts were cultured with or without all-trans retinoic acid in a three-dimensional collagen gel, and the extent of collagen degradation was determined by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Matrix metalloproteinase expression was examined by immunoblot analysis and gelatin zymography. The abundance and phosphorylation state of the endogenous nuclear factor-kappaB inhibitor IκB-α were examined by immunoblot analysis. Corneal ulceration was induced by injection of lipopolysaccharide into the central corneal stroma of rabbits and was assessed by observation with a slitlamp microscope.. All-trans retinoic acid inhibited interleukin-1β-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. It also attenuated the release and activation of matrix metalloproteinases as well as the phosphorylation and degradation of IκB-α induced by interleukin-1β in these cells. Topical application of all-trans retinoic acid suppressed corneal ulceration induced by injection of lipopolysaccharide into the corneal stroma.. All-trans retinoic acid inhibited collagen degradation mediated by corneal fibroblasts exposed to interleukin-1β, with this effect being accompanied by suppression of nuclear factor-kappaB signalling as well as of matrix metalloproteinase release and activation in these cells. All-trans retinoic acid also attenuated lipopolysaccharide-induced corneal ulceration in vivo. Our results therefore suggest that all-trans retinoic acid might prove effective for the treatment of patients with corneal ulceration.

Topics: Animals; Cells, Cultured; Collagen; Corneal Keratocytes; Corneal Ulcer; Disease Models, Animal; Dose-Response Relationship, Drug; Hydroxyproline; I-kappa B Proteins; Immunoblotting; Immunoenzyme Techniques; Interleukin-1beta; Keratolytic Agents; Lipopolysaccharides; Male; Matrix Metalloproteinases; NF-kappa B; Phosphorylation; Rabbits; Tretinoin