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T Claudepierre, MK Manglapus, N Marengi, L Bruckner-Tuderman, DD Hunter, WJ Brunken; Characterization of Collagen XVII in the Retina: A Potential Laminin Receptor> . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2695.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: An autoimmune response to collagen XVII (Bp180) produces a subepidermal blistering disease, bullous pemphigoid (BP) in humans. In basal epithelial cells, transmembrane Bp180 links elements of the hemidesmosomal plaque (Bpag-1) with laminin 5 in the basement membrane. Interestingly, patients suffering from BP exhibit neurological disorders, suggesting a new function for Bp180 in CNS. We hypothesize that Bp180 is a potential transmembrane receptor for the new laminins 14 and 15 we recently identified in the retina (α4ß2γ3 and α5ß2γ3 respectively). Methods: RT-PCR, in-situ hybridization, Western blots, immunoprecipitation and immunohistochemistry were performed to characterize the temporal and spatial expression of Bp180 in retina. In addition, we compared its distribution with its cytoplasmic ligand Bpag-1 (dystonin). Affinity column were used to test the interaction of Bp180 with ß2 containing laminins. Results: Immunoprecipitations from retina confirmed the identity of Bp180 as a molecule of 195kDa. Bp180 immunoreactivity is present along Müller fibers, in the outer plexiform layer (OPL), and as part of the interphotoreceptor matrix. In whole retina Bp180 is cleaved, resulting in smaller (130kDa) shed fragment as it is in keratinocytes. This isoform is not seen in Müller cells cultures, therefore cleavage is likely to be performed by an ectoenzyme produced by cells other than Müller cells in the retina. Interestingly we found full length Bp180 in synaptosome preparation indicating a synaptic expression of this transmembrane receptor. During development, Bp180 expression pattern follows synapse and outer segment maturation. In adult and developing retinae, Bp180 is co-localized with Bpag-1 at the OPL and in photoreceptor outer segments. Finally we determine that Bp180 has the ability to interact with ß2 containing laminins in the CNS. Conclusion: The overlapping distributions of Bp180 , dystonin, and ß2 containing laminins suggests that Bp180 participates in the formation of a desmosome-like structure and, thereby, plays a role in synapse stabilization by linking matrix and cytoskeletal components in the OPL. Bp180 may also play an addition role in stabilizing the outer segment and in the adhesion of the retina between the RPE and retina. Electroretinogram studies of patients suffering from BP should be performed to establish the function of this collagen in retina.
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