Latent TGFâ binding protein-1 and fibrillin-1 in human capsular opacification and in cultured lens epithelial cells

Background/aim—It was previously reported that collagenous extracellular matrix (ECM) in human capsular opacification contained isoforms of transforming growth factor â (TGFâ). In the present study, the authors performed immunohistochemistry to examine whether ECM in human capsular opacification and in cultures of bovine lens epithelial cells (LECs) contained latent TGFâ binding protein-1 (LTBP-1), TGFâ1 latency associated peptide (â1-LAP), and fibrillin-1, a suspected ligand of LTBP-1 as well as a component of the extracellular microfibrillar apparatus. The aim of the study was to further clarify the mechanism of TGFâ1 deposition in ECM of capsular opacification. Methods—Human capsular opacification specimens and uninjured lens capsules, as well as cultured bovine LECs, were processed for immunohistochemistry using antibodies against LTBP-1, â1-LAP, fibrillin-1, and collagen type I. Results—LTBP-1, â1-LAP, and fibrillin-1 all were localised to the ECM in human capsular opacification. Uninjured lens epithelium stained for â1-LAP, but not for LTBP-1 and fibrillin-1. ECM deposited in confluent LEC cultures stained for LTBP-1, â1-LAP, and fibrillin-1, while cultures with only sparse cellularity were unstained for LTBP-1 or fibrillin-1. Conclusions—LECs upregulate LTBP-1 and fibrillin-1 during postoperative healing. LTBP-1, â1-LAP, and fibrillin-1 colocalised to the ECM in capsular opacification and in confluent LEC cultures. TGFâ1 is considered to deposit in ECM in the large latent form. ECM secreted by LEC may function as a scavenger or repository of TGFâ. (Br J Ophthalmol 2001;85:1362–1366) Capsular opacification is the most common complication of implantation of an intraocular lens (IOL). Lens epithelial cells (LECs) are responsible for this occurrence, depositing extracellular matrix (ECM) on the capsule. LECs may transform to a mesenchymal-like phenotype and produce ECM components including collagens, the major components of capsular opacification, in some conditions. 5 LEC proliferation in association with ECM production is considered part of the wound healing process in the crystalline lens. Transforming growth factor â (TGFâ) is pivotal in regulating cell behaviour during wound repair. Three isoforms (â1, â2, and â3) are known in mammals. 7 Each isoform of TGFâ shows similar biological activities in vivo—that is, positive or negative regulation of cell growth, diVerentiation, and/or ECM production. Aqueous humour contains abundant TGFâ2. Moreover, healing LEC and ECM accumulation in capsular opacification reportedly contain TGFâ isoforms. 11 Macrophages adhering to IOL are also immunoreactive for TGFâ isoforms. These isoforms are secreted as inactive complexes including small and large latent forms. Small latent TGFâ is composed of active TGFâ plus TGFâ latency associated peptide (â1-LAP); the large latent form consists of the small latent form of TGFâ plus latent TGFâ binding protein (LTBP). The ECM reportedly acts as a scavenger or repository for TGFâ in various tissues. Fibrillin-1, a component of the extracellular microfibrillar apparatus, reportedly can bind to LTBP-1. 17 These two proteins share a number of features including multiple EGFlike repeats, the RGD sequence, and an eight cysteine repeat motif unique to this family of proteins. 17 Immunolocalisation of LTBP-1 and fibrillin-1, in capsular opacification has not Table 1 Summary of the cases and the results Case No Age* Sex Indication for Duration† IOL removal