Genetic Separation of the Human Lacritin Gene (“LACRT”) and Triple A (Allgrove) Syndrome on 12Q13
Molecular mechanisms underlying the pathogenic decline of secretory output by the main lacrimal gland, and subsequently dry eye, are potentially multiple. Inflammatory expansion of B and T lymphocytes can lead to loss of lacrimal acini.1 Curiously, however, acinar volume loss often appears insufficient relative to the theoretical overcapacity of the main lacrimal gland. Estimates suggest a potential secretory output up to 10-fold greater than required to maintain a normal aqueous tear film layer.2,3 Other mechanisms, therefore, warrant attention, such as aberrant secretion of one or several common cytokines that may directly or indirectly alter lacrimal acinar cell function and/or lead to a decline in neural innervation.4 Novel autocrine/paracrine factor(s) released by lacrimal acinar cells into the tear film may be required for the health of the lacrimal secretory machinery, ductal system and corneal epithelium.5 The periacinar basement membrane is also required for normal secretory function,6 in part via BM180 whose apparent synergy with laminin-1 promotes stimulated tear secretion.7,8 Alteration of each factor, together or independent of hormonal changes, could contribute to decreased secretory capacity.
KeywordsContact Lens Contact Lens Wear Lens Surface Microbial Keratitis Silicone Hydrogel
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- 4.D.A. Sullivan, L.A. Wickham, E.M. Rocha, K.L. Krenzer, B.D. Sullivan, R. Steagall, J.M. Cermak, M.R. Dana, M.D. Ullman, E.H. Sato, J. Gao, F.J. Rocha, M. Ono, L.A. Silveira, R.W. Lambert, R.S. Kelleher, D.B. Tolls, and I. Toda, Androgens and dry eye in Sj0gren’s syndrome. Ann NY Acad Sci. 876:312 (1999).CrossRefPubMedGoogle Scholar
- 6.L. Chen, J.D. Glass, S.C. Walton, and G.W. Laurie, Role of laminin-1, collagen IV, and an autocrine factor(s) in regulated secretion by lacrimal acinar cells, Am J Physiol. 275:C278 (1998).Google Scholar
- 8.G.W. Laurie, J.D. Glass, R.A. Ogle, C.M. Stone, J.R. Sluss, and L. Chen, “BM180”: a novel basement membrane protein with a role in stimulus-secretion coupling by lacrimal acinar cells, Am J Physiol. 270:C1743 (1996).Google Scholar
- 16.H. Lee, E. Choi, Y. Seomun, K. Montgomery, A. Huebner, E. Lee, S. Lau, C.-K. Joo, R. Kucherlapati, and K.S.-J. Yoon, High-resolution transcript map of the region spanning D12S1629 and D12S312 at chromosome 12q13: triple A syndrome-linked region, Genome Res. 10:1561 (2000).CrossRefPubMedPubMedCentralGoogle Scholar
- 17.A. Tullio-Pelet, R. Salomon, S. Hadj-Rabia, C. Mugnier, M.H. de Laet, B. Chaouachi, F. Bakiri, P. Brottier, L. Cattolico, C. Penet, M. Begeot, D. Naville, M. Nicolino, J.L. Chaussain, J. Weissenbach, A. Munnich, and S. Lyonnet, Mutant WD-repeat protein in triple-A syndrome, Nat Genet. 26:332 (2000).CrossRefPubMedGoogle Scholar