tretinoin and Eye-Injuries

Excessive wound contraction can lead to scar formation in the conjunctiva. The effects of all-trans-retinoic acid (ATRA) on the contractility of human Tenon fibroblasts (HTFs) cultured in three-dimensional (3D) collagen gels were investigated.. Human Tenon fibroblasts were cultured in 3D gels of type I collagen and in the absence or presence of TGF-β, ATRA, or various inhibitors. Collagen gel contraction was evaluated by measurement of gel diameter. Phosphorylation of various signaling molecules was examined by immunoblot analysis. The formation of actin stress fibers and focal adhesions was detected by laser confocal microscopy.. All-trans-retinoic acid inhibited TGF-β-induced collagen gel contraction mediated by HTFs in a concentration- and time-dependent manner. The TGF-β-induced phosphorylation of focal adhesion kinase (FAK) and formation of stress fibers and focal adhesions in HTFs were attenuated by ATRA. All-trans-retinoic acid also inhibited the TGF-β-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK) as well as that of c-Jun and Smad2/3. Furthermore, TGF-β-induced collagen gel contraction was blocked by inhibitors of ERK, p38, or JNK signaling.. All-trans-retinoic acid inhibited TGF-β-induced collagen gel contraction mediated by HTFs, most likely by attenuating the formation of actin stress fibers and focal adhesions as well as signaling by MAPKs, c-Jun, and Smads. All-trans-retinoic acid may therefore prove effective for inhibition of conjunctival scarring through attenuation of the contractility of Tenon fibroblasts.

Topics: Cells, Cultured; Cicatrix; Collagen; Conjunctiva; Eye Injuries; Fibroblasts; Humans; Imaging, Three-Dimensional; Immunoblotting; Microscopy, Fluorescence; Tenon Capsule; Transforming Growth Factor beta; Tretinoin; Wound Healing

The aim of the study was to investigate the possible healing effect of the vitamin A analogue all-trans retinoic acid 0.05% (RA) in vaseline on epithelial corneal abrasions in 13 ocularly healthy Copenhagen white rabbits.. A corneal abrasion with a diameter of 6 mm was created centrally in both eyes with a trephine and subsequent rubbing off of the corneal epithelium with an n-heptanol soaked swab The corneal abrasions were treated twice daily with topical applications (50 microl); RA was placed in the right inferior fornix and its vaseline vehicle in the left inferior fornix. Photographic documentation of fluorescein stained, non-healed areas, was performed at time points 0, 12, 24, 36, 48 and 72 h. The rabbits were sacrificed by an overdose of pentobarbital and enucleated. Planimetry was performed from corneal photographs.. Healed epithelial mean area at time point 36 h was significantly higher after RA compared to vehicle (p=0.036, paired t-test). Median time to 75% and 85% healing was significantly shorter for RA compared to vehicle (p= 0.03 and 0.02, log rank-test). No morphological difference, evaluated by light microscopy (hematoxylin-eosin) or scanning electron microscopy, was noted between the two treatments.. It is concluded that RA 0.05% applied twice daily increases the healing rate compared to vaseline vehicle.

Topics: Administration, Topical; Animals; Cornea; Corneal Injuries; Eye Injuries; Female; Fluorophotometry; Keratolytic Agents; Microscopy, Electron, Scanning; Ophthalmic Solutions; Rabbits; Tretinoin; Wound Healing; Wounds, Nonpenetrating