The anti-inflammatory and proresolution properties of lipid mediators in epithelial tissue in general are now well-established.
26 This study has characterized the profile of PCs, the most common of the phospholipids of cell membrane and the most prevalent in the mammalian cornea.
8 PCs serve a variety of functions including membrane structural support as well as cell signaling.
27 PCs and their hydrolysis products potentially play a role in corneal wound healing.
28 For example, lysophosphatidic acid and its homologues have been identified as mediators of cellular regeneration following corneal injury.
29 Thus, although the hydrolyzed lipids may be regarded as products of the damage process, their role as promoters of wound healing and repair process cannot be ruled out. Indeed, we found that some lipids (likely to be phospholipids) generated within 30 seconds of 11 M NaOH exposure (rapidly lost when the alkali exposure continues for more than 5 minutes) dramatically promote wound healing (see Supplementary Material and
Supplementary Fig. 1). Previously PCs have been shown to play a role in the inhibition of alkali-burn induced lipoxygenation. Platelet activating factor (PAF; 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a PC membrane lipid plays a role in inflammation following corneal alkali exposure.
30 A PAF antagonist (BN 52021) has been shown to inhibit lipoxygenase reactions, and the accumulation of PAF has been linked to corneal damage after alkali exposure.
30,31 Our data (see Supplementary Material and
Supplementary Tables S1,
S2) are consistent with up-regulation of PAF in corneal alkali exposures. Furthermore, as the time period of alkali exposure increased, there was an observable up-regulation of PAF in the treated porcine eyes (see Supplementary Material and
Supplementary Tables S1,
S2), comparable to the trend found in rabbit eyes in prior studies.
31 The average amount of PAF present in control porcine corneal tissue (7.56 pmol/μg of protein) increased in treated groups; that is, from 30 seconds to 30 minutes (from 10.56–69.57 pmol/μg; see Supplementary Material and
Supplementary Table S1). However, at 60 minutes of alkali exposure, the quantity of PAF present decreased. We conjecture that this was due to the hydrolysis of PAF. In the alkali-exposed human corneal tissue, the PAF species PC(O-18:2(9Z,12Z)/2:0) followed the same trend, ultimately decreasing at 60 minutes (see Supplementary Material and
Supplementary Table S2). The detailed knowledge of changes in PC species and subsequent elucidation of their role in biological processes will help guide their use in clinical settings. For example, wound-healing PCs could be used in severely damaged cornea for rapid promotion of repair processes.