TEAR FILM & OCULAR SURFACE TEARS TODAY: UNDERSTANDING DRY EYE IN 2004. Anthony J. Bron. Nuffield Laboratory of Ophthalmology, University of Oxford. Purpose. To provide a critical account of dry eye disease. Methods. Literature review. Results. Tears are the point of confluence of a system coordinated to maintain eye health. In dry eye disease this system breaks down, leading to surface inflammation and discomfort, from either aqueous or lipid tear deficiency (ATD or LTD) or both. Diagnosis is based on symptoms and the demonstration of tear instability, surface damage and tear hyperosmolality. Causal attribution requires additional tests. ATD is due to lacrimal dysfunction, with a fall in lacrimal proteins, tear flow or volume. Dysfunction may be age-related, or less commonly, a feature of Sjögren’s Syndrome. In either case an autoimmune lymphocytic infiltration of the lacrimal gland and conjunctiva lead to tissue destruction. LTD is most commonly due to meibomian gland dysfunction (MGD), either primary, or secondary to acne rosacea, or atopic or seborrhoeic dermatitis. A diagnosis of MGD depends on evidence of obstruction and reduced oil expressability, a depleted reservoir and thinning of the precorneal oil film with altered spreading. Attribution of dry eye to MGD alone is based on the clinical features of MGD in the presence of normal lacrimal function. When ATD coexists with MGD, diagnosis is difficult and increased tear evaporation is likely to be the only reliable criterion of evaporative dry eye. Over the past decade new concepts have been advanced concerning the integration of lacrimal, meibomian, and conjunctival secretion and the regulatory roles of hormonal and neural factors. The technology to explore this in health and disease has kept pace with these ideas. Sophisticated methods are available to measure lacrimal secretion, evaporation, tear osmolality and the thickness of the tear film and its lipid layer. Micro-techniques offer the possibility to measure almost any component of the tears in a minimally invasive manner, whether proteins, lipids, mucins, growth factors, defence molecules or inflammatory mediators. Conclusions. With new therapies in view, such as secretagogues, hormones and immune modulators, we need to be able to stage dry eye realistically and distinguish reversible from irreversible disease. For this we need to establish key markers of dry eye and prospective studies of its natural history. The tools are now available to unlock its secrets. Commercial Relationship(s):Alcon; Allergan; CAT; Daiichi; Kowa; Ocusense; Santen; Senju; Takeda. Grants: Nil
PECAM-1 (CD31) IS REQUIRED FOR OPTIMAL NEUTROPHIL MIGRATION IN A MOUSE MODEL OF CORNEAL WOUND HEALING. Alan R. Burns,1 Evelyn S. Brown,1 Debjani Gagen,2 C. Wayne Smith,2 Zhijie Li.2 Department of Medicine, Baylor College of Medicine, Houston, TX USA;1 Department of Pediatrics, Baylor College of Medicine, Houston, TX.2 Purpose. PECAM-1 is expressed on endothelial cells and leukocytes. In some settings, PECAM-1 regulates leukocyte migration across inflamed endothelium. As well, PECAM-1 ligation can activate leukocyte integrins, thereby facilitating adhesive interactions with the extracellular matrix (ECM). Using a defined injury to corneal epithelium, we chose to investigate the role of PECAM-1 on neutrophil (PMN) migration in the cornea. Methods. C57BL/6 wild type mice and mice deficient in PECAM-1 were anesthetized with Nembutal. Corneal epithelial wounds were made through the whole epithelium with a trephine and the epithelium within the lesion was removed, leaving the basement membrane intact. Injured corneas were excised at 6h intervals, fixed and fluorescently labeled with a nuclear stain (DAPI) and an anti-PMN antibody (Gr-1-FITC). PMN influx was assessed by counting Gr-1 positive cells displaying nuclear lobulation. PMN transendothelial migration efficiency in vitro was assessed by videotape analysis of mouse PMN migration across interleukin-1 (IL-1)-activated mouse venous endothelial monolayers. The amount of PMN surface contact with corneal ECM elements and resident cells (keratocytes) was assessed by transmission electron microscopy. Results. Following corneal injury, peak PMN influx is delayed in PECAM-1-deficient mice (18h versus 12h in the wild type) and the magnitude of the response is diminished by 30%. The rate of PMN migration across IL-1-activated endothelium is not affected by the absence of PECAM-1. Electron microscopy reveals that PMN migration within the corneal stroma involves adhesive contacts not only with ECM elements, but also resident cells (keratocytes). Conclusions. PECAM-1 is required for efficient PMN migration in the corneal stroma, but not for migration across the endothelium. Efficient migration within the stroma involves PMN interactions with both ECM elements and keratocytes. Our data support the concept that PECAM-1 plays a signaling role and that PECAM-1 is necessary for optimal integrin activation and efficient PMN surface interactions with ECM and keratocytes.
THE OCULAR SURFACE / JANUARY, 2005, VOL. 3, NO. 1 / SUPPLEMENT