transforming-growth-factor-beta and Pseudophakia

Posterior Capsule Opacification (PCO) is the most common complication of cataract surgery. At present the only means of treating cataract is by surgical intervention, and this initially restores high visual quality. Unfortunately, PCO develops in a significant proportion of patients to such an extent that a secondary loss of vision occurs. A modern cataract operation generates a capsular bag, which comprises a proportion of the anterior and the entire posterior capsule. The bag remains in situ, partitions the aqueous and vitreous humours, and in the majority of cases, houses an intraocular lens. The production of a capsular bag following surgery permits a free passage of light along the visual axis through the transparent intraocular lens and thin acellular posterior capsule. However, on the remaining anterior capsule, lens epithelial cells stubbornly reside despite enduring the rigours of surgical trauma. This resilient group of cells then begin to re-colonise the denuded regions of the anterior capsule, encroach onto the intraocular lens surface, occupy regions of the outer anterior capsule and most importantly of all begin to colonise the previously cell-free posterior capsule. Cells continue to divide, begin to cover the posterior capsule and can ultimately encroach on the visual axis resulting in changes to the matrix and cell organization that can give rise to light scatter. This review will describe the biological mechanisms driving PCO progression and discuss the influence of IOL design, surgical techniques and putative drug therapies in regulating the rate and severity of PCO.

Topics: Animals; Cataract; Cataract Extraction; Cell Proliferation; Epithelial Cells; Humans; Lens Capsule, Crystalline; Lenses, Intraocular; Postoperative Complications; Pseudophakia; Signal Transduction; Transforming Growth Factor beta

Pseudophakic bullous keratopathy (PBK) is a major indication for corneal transplantation. Previous studies showed that PBK corneas had increased levels of insulin-like growth factor-I (IGF-I), bone morphogenetic protein-4 (BMP-4), transforming growth factor-beta (TGF-beta), interleukin-1alpha (IL-1alpha) and IL-8. The PBK corneas also had accumulations of tenascin-C (TN-C), fibrillin-1 (Fib-1), matrix metalloproteinase-2 (MMP-2), inflammatory cells but not myofibroblasts. Our goal is to determine if the growth factors/cytokines that are elevated in PBK corneas alter the expression of extracellular matrix (ECM) and/or degradative enzymes in vitro.. Stromal cell cultures from normal and PBK human corneas were established and treated for 6 days with IGF-I, BMP-4, IL-1alpha, IL-8 or TGF-beta1/beta2. Immunostaining, Western blot and dot blot analyses for TN-C, Fib-1, alpha-smooth muscle actin (alpha-SMA, a marker for myofibroblasts) or tissue inhibitor of metalloproteinase-1 (TIMP-1) were performed. RNAs were collected and analyzed with Northern blots for TN-C, Fib-1 and beta(2)-microglobulin. Culture media were analyzed using gelatin zymography with or without ethylenediaminetetraacetic acid (EDTA). Some samples were activated with p-aminophenylmercuric acetate (APMA) and reduction/alkylation, and the degradative activities were measured by the MMP-gelatinase activity assay kit.. The IGF-I and TGF-beta1/TGF-beta2 increased (a) TN-C protein deposition, and (b) Fib-1 protein and RNA levels, but (c) had no significant affect on TIMP-1, matrix metalloproteinase-2 (MMP-2) or gelatinase activities. TGF-beta1/TGF-beta2 induced alpha-SMA protein (myofibroblasts) while IGF-I did not. BMP-4, IL-1alpha and IL-8 had little affect on the cells.. Based upon our data, the fibrotic markers, TN-C and Fib-1, found in PBK corneas may be accounted for by IGF-I and TGF-beta. These growth factors promote fibrosis and ECM deposition without promoting proteolysis. While the other growth factors/cytokines are elevated in PBK corneas, their role(s) in PBK pathogenesis are not clear. In addition, exogenous IGF-I most closely elicited a response that was most similar to the characteristics of the PBK/ABK corneas, i.e. accumulation of TN-C and Fib-1 proteins in the absence of myofibroblasts.

Topics: Blotting, Northern; Blotting, Western; Cells, Cultured; Corneal Diseases; Extracellular Matrix; Fibrillin-1; Fibrillins; Humans; Insulin-Like Growth Factor I; Matrix Metalloproteinases; Microfilament Proteins; Pseudophakia; Stromal Cells; Tenascin; Transforming Growth Factor beta

This study was carried out to investigate the distribution of transforming growth factor-beta1 (TGF-beta1) and the extracellular matrix (ECM) glycoprotein tenascin in secondary cataract and anterior subcapsular cataract.. Twenty-four pseudophakic human eyes with secondary cataract, obtained at autopsy 1 d to 10 yr (mean 2.4 yr) after cataract surgery, were studied. Additionally, a specimen from an anterior subcapsular cataract was included. Immunohistochemistry was used to localize TGF-beta1 and tenascin in secondary cataract and in anterior subcapsular cataract.. Polyclonal antibody to TGF-beta1 immunolabelled spindle-shaped cells in the plaques of secondary cataract in all eyes. Instead, the cells present in Soemmering's ring cataract were not labelled. The ECM in the plaques of secondary cataract was immunoreactive for tenascin in all eyes. In anterior subcapsular cataract spindle-shaped cells and ECM showed similar immunoreactivity.. Spindle-shaped cells that are immunolabelled with TGF-beta1 and ECM showing tenascin-like-immunoreactivity are present in secondary cataract and in anterior subcapsular cataract, thus implicating a possible role in secondary cataract.

Topics: Aged; Aged, 80 and over; Biomarkers; Cadaver; Cataract; Cataract Extraction; Eye Proteins; Female; Humans; Immunoenzyme Techniques; Lens Capsule, Crystalline; Male; Middle Aged; Pseudophakia; Tenascin; Transforming Growth Factor beta; Transforming Growth Factor beta1