RETINOIC ACID INHIBITS FORMATION OF MESENCHYME FROM LENS EPITHELIUM IN COLLAGEN GELS

Purpose. To examine the possibility that retinoic acid (RA), a stabili zer of the epithelial phenotype, would inhibit formation of mesenchyma l cells from avian lens epithelium in three-dimensional collagen. Meth ods. Lens epithelia from 11-day-old chick embryos were cultured for 6 days in collagen gels in the presence of RA. The number of mesenchymal cells emigrating into the gels was quantitatively compared with contr ol cultures to which RA was not added. Results. It was found that few fibroblast-like cells form at the highest dose used (10(-5) M RA) and outgrowth approaches control levels at lower doses of RA. The mesenchy mal cells that form after RA treatment are not ultrastructurally diffe rent from those of controls. Many have well-developed rough endoplasmi c reticulum and undoubtedly produce the collagen fibrils that accumula te around the cells. Others, although spindle-shaped, still exhibit le nslike cytoplasm. New basement membrane is deposited on the former fre e surface of RA-treated lens epithelium, but is not present at the for mer free surface of control epithelium. Conclusions. It is possible th at RA inhibition of lens transformation to fibroblast-like cells is at least partly due to the ability of RA to stimulate production of base ment membrane components by epithelia. More studies of RA action on ep ithelial-mesenchymal transformation in collagen gels may reveal additi onal mechanisms. It is also suggested that mesenchymal genes similar t o those activated in lens epithelium by suspension in collagen may tur n on in pathologic transformations (ie, in anterior capsular cataract, fibroblast-like cells arise from lens epithelium).