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Secreted phospholipase A2 type IIA (sPLA2-IIA) is a well-established pro-inflammatory protein and has been a major target for drug discovery. However, the mechanism of its signaling action has not been fully understood. We previously found that sPLA2-IIA binds to integrins αvβ3 and α4β1 in human and that this interaction plays a role in sPLA2-IIA's signaling action. Our recent studies found that sPLA2-IIA activates integrins in an allosteric manner through direct binding to a newly identified binding site of integrins (site 2), which is distinct from the classical RGD-binding site (site 1). The sPLA2-IIA-induced integrin activation may be related to the signaling action of sPLA2-IIA. Since sPLA2-IIA is present in normal human tears in addition to rheumatoid synovial fluid at high concentrations the sPLA2-IIA-mediated integrin activation on leukocytes may be involved in immune responses in normal and pathological conditions.

It was my great pleasure to have had the opportunity to give the conference address in addition to being honored by the Professor Dohlman Award. I am proud of the progress in the understanding of dry eye that has been made over the past couple of decades. However, the clinical application of the knowledge that has accumulated lies in the future. Thus far no effective medication has ever been developed for the treatment of severe dry eye. Cyclosoporine may become the first eyedrops to be used, and a series of new drugs containing androgens, immunomodulators, secretagogues, P2Y2 receptor agonists, and others may follow. I believe that medication for the treatment of dry eye will be developed in the not to distant future, and I hope that at the 4th conference in a few years time, we will be able to share these new treatments for the management of dry eye patients.

The Langmuir trough approach to the study of the physical properties of an in vitro system representing the natural tear lipid-aqueous interface gives useful information on the effect produced by changes of composition of both phases. We found that variations of the composition of the lipid mixture affect more strongly the characteristics of the film rather than changes in the aqueous phase composition. Therefore, future investigations should consider the possibility of searching for and optimising additions of lipid mixtures to the natural tear film. These novel mixtures should stabilise the lipid layer, and thus treat the evaporative Dry Eye Syndrome. More critical and worthy of further investigation is the effect of surface-active water-soluble components that can reduce and ultimately destroy the lipid film integrity and effectiveness. The beneficial effect of water-soluble components, either naturally occurring or artificially added, may be more precisely compared with possible side effects on the stability of the lipid tear layer. In any case, these side effects may be largely compensated by the presence of stability enhanced lipid composition. The present work may be considered as an introductory investigation that takes the physical-chemical approach into the realm of debated data about the tear film structure and properties. Refining the model we have adopted in the present work is certainly necessary. For instance, introducing into the model tear composition other components such as ceramides and cerebrosides will provide insight to their contribution to the packing structure. We may also couple different techniques such as measuring elastic and rheological properties of the films that may be relevant to its physiological behaviour.

In summary, tear EGF levels correlate most strongly with tear production in normals, and it is likely that some form of homeostatic mechanism exists to provide a constant supply to the ocular surface. Commercial ELISA kits appear to measure EGF in tears with good consistency and may be useful in the future to improve comparability of data from different studies. In addition, in ocular rosacea, which mimics keratoconjunctivitis sicca in a number of respects, there is a differential increase in the level of the inflammatory cytokine IL-1 alpha in the tear fluid. Much of this elevation appears to be the result of reduced tear turnover, which may form an important positive feedback mechanism encouraging tear stagnation and the perpetuation of ocular surface inflammation.

Meibomian gland disease--and, in particular, obstructive meibomian gland disease--makes an important contribution to ocular surface disease, in the form of meibomian keratoconjunctivitis. With improved methods for the study of meibomian oil composition and function, we are moving closer to the possibility of distinguishing the contribution of meibomian deficiency, as opposed to inflammatory events, to this disorder. More importantly, where aqueous tear deficiency and meibomian gland disease coincide in patients with dry eye, we are closer to the possibility of distinguishing their relative contributions to the dry eye state. This has implications for future therapies.

After reviewing the results of available methods for defining the dry eye with an exact assessment of severity, we found that micropachometry was the most sensitive. The following is a ranking of the other tests according to usefulness: Tear resistance, Schirmer, and BUT. Rose bengal stained eyes were usually decompensated; the meniscus test's primary use was as an "all or nothing" indicator, but recording the widths of extant menisci were unproductive.

The ability of taurine to protect biomembranes attacked by HOCl was examined using canine erythrocytes which had been pre-treated with HOCl. Of the amino acids tested, taurine was the most effective in inhibiting attack by HOCl, followed by glycine, alpha-alanine and beta-alanine. During the incubation of HOCl-treated erythrocytes with taurine, an appreciable amount of monochlorotaurine (TauNHCl) was detected in the supernatant. This suggests that taurine may remove the oxidized chlorine from HOCl-treated erythrocytes, resulting in the production of TauNHCl. The effect of taurine on the removal of Cl+ moiety was examined using Sepharose gel with amino groups. Taurine removed Cl+ from HOCl-treated Sepharose gel. The yield of TauNHCl depended on the concentration of taurine. The effectiveness of taurine in preventing ocular surface damage caused by HOCl was investigated in albino rabbits. The activity of lactate dehydrogenase (LDH) released from ocular tissues into tears during eye irritation was used as an index of ocular surface damage. Taurine effectively protected ocular surface tissues from damage induced by HOCl, and arrested the progression of tissue damage that had already been initiated by HOCl. These finding suggest that taurine may be clinically useful in the treatment of ocular surface damage caused by oxidants such as HOCl.