Retinoids and butyrate modulate fibroblast growth and contraction of collagen matrices

Wound healing in the eye may lead to undesirable sequelae such as proliferative vitreoretinopathy and scarring of glaucoma filtering fistulas. We therefore sought to manipulate in vitro two key wound healing processes--cell proliferation and contraction of extracellular matrices--using vitamin A (VA), retinoic acid (RA), and n-butyrate (BUT). These substances modulate growth and differentiation of normal and neoplastic cells. We examined the effects of these agents on cultured rabbit fibroblast proliferation and contraction of collagen matrices. Dermal fibroblast proliferation was unaffected by VA, stimulated by RA, and inhibited by BUT. Scleral fibroblast proliferation, in contrast, was stimulated by both VA and RA. All three agents mildly inhibited fibroblast contraction of collagen matrices. We conclude that 1) VA, RA, and BUT have differential effects on rabbit fibroblast proliferation; 2) retinoid effects on fibroblast growth vary with the tissue of origin; and 3) VA, RA, and BUT modestly inhibit fibroblast contraction of extracellular matrices. This study suggests that fibroblast-mediated processes in ocular wound healing and cicatricial disease may be differentially modulated by retinoids and BUT.