Dry eye in postmenopausal women: a hormonal disorder.

OBJECTIVE: This review examines the etiology and pathophysiology of dry eye disease in postmenopausal women, and describes the steroid reproductive hormone influences that may contribute to its development. METHODS: We have reviewed the relevant studies on dry eye disease related to hormonal status and hormone therapy (HT) in both animal models and humans. RESULTS: Although both low and high estrogen levels have been associated with symptoms of dry eye disease, low androgen levels are a more consistent factor in its etiology. Postmenopausal HT with estrogen or estrogen plus progestogen has shown a limited benefit for dry eye symptoms and may even result in progression of meibomian gland dysfunction, decreased tear film break up time, and tear flow reduction. However, systemic or local androgen treatment has shown promising results in improving dry eye symptoms. CONCLUSIONS: Because of the high incidence of dry eye among postmenopausal women that may be related to the hormonal treatment, we propose that a multidisciplinary approach should be considered between gynecologists and ophthalmologists in management of this disorder.

Potentially pathogenic immune cells and networks in apparently healthy lacrimal glands.

Lacrimal glands of people over 40 years old frequently contain lymphocytic infiltrates. Relationships between histopathological presentation and physiological dysfunction are not straightforward. Data from rabbit studies have suggested that at least two immune cell networks form in healthy lacrimal glands, one responding to environmental dryness, the other to high temperatures. New findings indicate that mRNAs for several chemokines and cytokines are expressed primarily in epithelial cells; certain others are expressed in both epithelial cells and immune cells. Transcript abundances vary substantially across glands from animals that have experienced the same conditions, allowing for correlation analyses, which detect clusters that map to various cell types and to networks of coordinately functioning cells. A core network--expressing mRNAs including IL-1α, IL-6, IL-17A, and IL-10--expands adaptively with exposure to dryness, suppressing IFN-γ, but potentially causing physiological dysfunction. High temperature elicits concurrent increases of mRNAs for prolactin (PRL), CCL21, and IL-18. PRL is associated with crosstalk to IFN-γ, BAFF, and IL-4. The core network reacts to the resulting PRL-BAFF-IL-4 network, creating a profile reminiscent of Sjögren's disease. In a warmer, moderately dry setting, PRL-associated increases of IFN-γ are associated with suppression of IL-10 and augmentations of IL-1α and IL-17, creating a profile reminiscent of severe chronic inflammation.

A lacrimal gland is a lacrimal gland, but rodent's and rabbit's are not human.

Research into the physiological processes governing both normal and abnormal functions of the lacrimal gland has used animal models to provide insights that might be applied to improving our understanding of human disease and designing of beneficial therapeutic interventions. Animal models most frequently used are mice, rats, and rabbits. As participants in research into normal and abnormal lacrimal gland function, the authors have observed significant differences between the various animal models, and these differences must be considered in investigational studies. This review summarizes a wide range of topics, including structural organization of the lacrimal gland and the immunological, secretomotor and hormonal processes regulating lacrimal gland function in all three animal models. In addition, comparisons with relevant aspects of the human lacrimal gland are included where permitted by available data.

Establishing a regional medical campus in southeast Florida: successes and challenges.

In August 2007, the first class of University of Miami Miller School of Medicine (UM) medical students will begin the four-year undergraduate medical education program at the regional medical campus at Florida Atlantic University (FAU) The authors describe how UM and FAU were able to make a successful case to state policymakers for a regional medical campus as a cost-effective approach to expanding undergraduate and graduate medical education opportunities in southeast Florida The authors discuss what motivated UM and FAU to partner to create a regional medical campus, and they describe the challenges that have been encountered since 2004, particularly those relating to delivering a comparable two-year program on two campuses using distance-learning technologies. The opportunities that have resulted from expansion of the regional campus from two to four years are also described, including the development of a new and innovative four-year curriculum emphasizing comprehensive chronic disease management and case-based and patient-centered education using collaborative, small-group student learning communities. UM medical students thus have a choice between two educational tracks. The authors conclude that no significant impediments have resulted from the Florida collaboration between a public and a private university and that the regional medical campus model can serve as a viable option for other states and institutions attempting to expand medical school enrollment and meet physician workforce needs in an efficient and cost-effective manner.

Heterotrimeric GTP-binding proteins in the lacrimal acinar cell endomembrane system.

Secretagogues accelerate traffic in the lysosomal and basal-lateral pathways, as well as in the regulated apical secretory pathway, of lacrimal acinar cells. It has been proposed that alterations of protein segregation in compartments where these traffic pathways intersect may influence autoimmune responses. Heterotrimeric GTP-binding proteins couple secretagogue receptor ligand binding to activation of intracellular signaling cascades, but they are also suggested to participate in endomembrane traffic phenomena. Distributions of G(o), G(i3), G(q), G(11), and two G(s)isoforms were mapped in reconstituted lacrimal acini by confocal immunofluorescence microscopy and in lysates of the reconstituted acini by analytical subcellular fractionation. All G proteins examined were detected at low levels in isolated compartments (blm(i,j)) believed to represent the basal-lateral plasma membrane. G(i3), G(11), and the G(s)isoforms were concentrated in a series of isolated compartments believed to be related to domains of a basal-lateral endosome with sorting and recycling functions (ble-s/r(i,j,k)), a distinct endosomal compartment with basal-lateral membrane-like composition (e-blml), and domains of the trans-Golgi network believed to be involved in traffic to and from the basal-lateral membrane (tgn-blmr). G(o)and G(q)were concentrated in compartments believed to represent a mixture of immature and mature secretory vesicle membranes (isvm and svm) and domains of the trans-Golgi network compartment believed to mediate traffic to secretory vesicles (tgn-svr) and to pre-lysosomes (tgn-lr). Confocal fluorescence microscopy confirmed the presence of both basal-lateral membrane and intracellular pools of the G proteins. Stimulation with 10 microM carbachol for 20min caused a component of the G(o)to redistribute away from the isvm+svm; components of the G(i3), G(q), and G(s)to redistribute away from the tgn-svr+tgn-lr; and a component of the G(i3)to redistribute away from the ble-blml+tgn-blmr. Thus, these proteins may participate in endomembrane traffic steps activated by cholinergic stimulation in addition to playing their classical roles in plasma membrane signal transduction.