GROWTH FACTOR-LIKE PHOSPHOLIPIDS GENERATED AFTER CORNEAL INJURY

The present study provides evidence that growth factor-like glyceropho sphate mediators of the lysophosphatidic acid (LPA) family are present in the aqueous humor and the lacrimal gland fluid of the rabbit eye. By use of a combination of HPLC, two-dimensional TLC, mass spectrometr y, and the Xenopus oocyte bioassay, the LPA-like phospholipids LPA, cy clic PA, alkenyl-glycerophosphate (GP), lysophosphatidylserine, and ph osphatidic acid were detected as physiological constituents of the flu ids bathing the cornea. Corneal injury resulted in an increased produc tion of some of these mediators. Alkenyl-GP, a novel member of the LPA family, has been identified in postinjury aqueous humor, establishing that it is generated endogenously. LPA and its homologues were found to be mitogenic in freshly dissociated keratocytes from uninjured corn eas. There appears to be a link between the occurrence of LPA responsi veness in keratocytes activated by injury and the increase in LPA-like activity in aqueous humor. These data suggest that LPA and its homolo gues are involved in maintaining the integrity of the normal cornea an d in promoting cellular regeneration of the injured cornea.