transforming-growth-factor-beta and Retinal-Detachment

Proliferative vitreoretinopathy (PVR) is the major cause of failure in patients undergoing surgery for rhegmatogenous retinal detachment (RRD). Characterized by the formation of an abnormal contractile membrane within the eye, PVR can cause tractional retinal redetachment. Epithelial-to-mesenchymal transition (EMT), in which epithelial cells morphologically and phenotypically transdifferentiate into mesenchymal cells, is the major pathological process implicated in PVR. Among the various cell types involved in the process, retinal pigment epithelium cells are primary contributors although, after decades of research, the mechanisms underlying EMT have remained elusive. Recently, signaling pathways, some involving growth factors, have been demonstrated to contribute to EMT. In this article, we review research to date about the roles of such signaling, including including transforming growth factor-beta-, hepatocyte growth factor-, platelet-derived growth factor-, and Notch-, Wnt/β-catenin-, and Hippo-signaling pathways, in the EMT of PVR.

Topics: beta Catenin; Calcium-Binding Proteins; Epithelial-Mesenchymal Transition; Hepatocyte Growth Factor; Hippo Signaling Pathway; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Platelet-Derived Growth Factor; Protein Serine-Threonine Kinases; Receptors, Notch; Retinal Detachment; Serrate-Jagged Proteins; Signal Transduction; Transforming Growth Factor beta; Vitreoretinopathy, Proliferative; Wnt Signaling Pathway

Full-thickness macular holes generally cause a significant reduction in visual acuity, due in part to a rim of surrounding neurosensory retinal detachment and retinal thickening. Recent studies have suggested that flattening of this narrow rim of neurosensory detachment can result in improved visual acuity. However, the ability to flatten the neurosensory detachment is limited using current surgical techniques.. Transforming growth factor-beta 2 (TGF-beta 2) is a recently discovered potent stimulator of wound healing. The authors, therefore, performed a prospective randomized study of 60 patients to determine if the local application of TGF-beta 2 to the edge of the macular hole can reproducibly induce flattening of the surrounding neurosensory detachment. The results of a study designed to determine the effect of a pars plana vitrectomy, fluid-gas exchange, and intravitreal instillation of TGF-beta 2 in eyes with a full-thickness macular hole and reduced visual acuity are reported.. After treatment, visual acuity improved 2 lines or more in 5 of 11 eyes treated with 70 ng, in 4 of 12 eyes treated with 330 ng, and in 10 of 11 eyes treated with 1330 ng of TGF-beta 2. In some eyes, hyaluronic acid was added. In these cases, visual acuity improved 2 lines or more in 0 of 9 eyes treated with 70 ng TGF-beta 2, in 2 of 8 eyes treated with 330 ng, and in 4 of 9 eyes treated with 1330 ng.. Logistic regression analysis demonstrated a statistically significant beneficial effect of TGF-beta 2 on visual improvement (P = 0.003).

Topics: Adolescent; Adult; Aged; Child; Female; Fluorescein Angiography; Fundus Oculi; Humans; Male; Middle Aged; Prospective Studies; Retinal Detachment; Retinal Perforations; Transforming Growth Factor beta; Visual Acuity; Vitrectomy; Wound Healing

Rhegmatogenous retinal detachment (RRD) is caused by one or more full-thickness retinal breaks. The current RRD treatments have several drawbacks. Chitosan is one of the most commonly used natural polymers for wound healing and has been demonstrated to be biodegradable, biocompatible, non-toxic, bioadhesive, and bioactive. This study aimed to determine the reliability and effectiveness of chitosan for sealing retinal breaks in rabbits.. Eighteen blue purple rabbits were randomly divided into three groups: chitosan (n = 6), RRD (n = 6), and control (n = 6). The RRD model was established using vitrectomy, making retinal holes, and subretinal fluid injection in the RRD and chitosan groups. One week after the establishment of the model, chitosan was applied within the range of the holes in the chitosan group, and the vitreous body was filled with perfusion fluid. Except the chitosan treatment, the RRD group underwent the same procedure. Intraocular pressure (IOP) measurement, fundus photography, B-mode ultrasound, optical coherence tomography (OCT), histology, and enzyme linked immunosorbent assay (ELISA) were performed.. Retinas of all eyes in the RRD group were detached, whereas those of all eyes in the chitosan group remained attached. The concentrations of epidermal growth factor (EGF), fibroblast growth factor (FGF)-2, transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and IL-8 in the vitreous fluid of the RRD group were significantly higher than those of the control group (. Chitosan may be a reliable method for sealing retinal breaks. Moreover, chitosan can maintain high levels of growth factors and reduce inflammatory factors in the vitreous, which may reduce and delay the death of retinal cells and help restore visual function after retinal repositioning.

Topics: Animals; Chitosan; Epidermal Growth Factor; Interleukin-6; Interleukin-8; Rabbits; Reproducibility of Results; Retinal Detachment; Retinal Perforations; Retrospective Studies; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

The cytokine transforming growth factor-ß (TGF-ß) is a pivotal contributor to tissue fibrosis and a key cytokine in the pathogenesis of cellular transdifferentiation, epithelial-mesenchymal transition (EMT), and cell adhesion. This study evaluates the effect of decorin, a naturally occurring TGF-ß inhibitor, in an experimental rabbit model for proliferative vitreoretinopathy (PVR).. Traumatic PVR was induced in 50 rabbits divided into ten groups (n = 5). One group (GI) reveals a control with no treatment after trauma. Groups (GII-GIV) consisted of subgroups receiving phacovitrectomy at three different time points; (a) at the time of trauma, (b) 1 week following trauma, and (c) 2 weeks following trauma. GIII and GIV received 100 μg or 200 μg decorin, respectively. PVR severity was scored from 0 to 4. The amount of fibrosis was quantified using JMicroVision© software.. The control group GI developed severe PVR with tractional retinal detachment (TRD); (PVR score ≥2) in four rabbits out of five. Vitrectomy had a positive effect (p < 0.05) on PVR development when preformed immediately, however the developed fibrosis was high. The best results were obtained when surgery was used in conjunction with decorin that reduced both the PVR score and fibrosis development significantly (p < 0.05). Depending on dosage and time of vitrectomy, PVR could be completely avoided (PVR score = 0) in 16 rabbits out of 30. TRD was prevented in 13 rabbits out of 15 in GIII to 14 rabbits out of 15 in GIV. In decorin-treated eyes, vitrectomy outcome was best when preformed at 1 week after trauma. There were no drug-related toxic effects evident on clinical and histopathological examination.. In conclusion, in this rabbit model of PVR, adjuvant decorin application during vitrectomy effectively reduces fibrosis and TRD development. In conjunction with no obvious histopathological toxicity signs, decorin represents a promising substance to inhibit PVR reactions.

Topics: Animals; Decorin; Disease Models, Animal; Female; Fibrosis; Intravitreal Injections; Phacoemulsification; Rabbits; Retina; Retinal Detachment; Transforming Growth Factor beta; Vitrectomy; Vitreoretinopathy, Proliferative

We generated a mouse model (cKO) with a conditional deletion of TGF-beta signaling in the retinal neurons by crossing TGF-beta receptor I (TGF-beta RI) floxed mice with nestin-Cre mice. Almost all of the newborn cKO mice had retinal detachment at the retinal pigment epithelium (RPE)/photoreceptor layer junction of the neurosensory retina (NSR). The immunostaining for chondroitin-6-sulfate showed a very weak reaction in cKO mice in contrast to intense staining in the photoreceptor layer in wild-type mice. Macroscopic cataracts, in one or both eyes, were observed in 50% of the mice by 6 months of age, starting as early as the first month after birth. The cKO mouse model demonstrates that the TGF-beta signaling deficiency in retinal cells leads to decreased levels of chondroitin sulfate proteoglycan in the retinal interphotoreceptor matrix. This in turn causes retinal detachment due to the loss of adhesion of the NSR to RPE.

Topics: Animals; Cataract; Mice; Mice, Knockout; Mice, Transgenic; Retinal Detachment; Signal Transduction; Transforming Growth Factor beta

To study the involvement of apoptosis using different apoptosis markers in PVR pathogenesis.. The presence of mRNA coding for Fas, Fas ligand (FasL), and TNF-related apoptosis inducing ligand (TRAIL) was investigated in vitreous samples from 46 consecutive patients-25 with PVR, 11 with retinal detachment (RD) not complicated by PVR, and 10 with macular hole (MH)-using RT-PCR. From previously examined vitreous samples, 21 PVR, 9 RD, and 10 MH were examined for their levels of TGF-beta2 protein with sandwich ELISA kits. Five epiretinal membranes excised from five patients with PVR were also examined for apoptotic cell death using the terminal deoxytransferase (TdT) mediated dUTP-biotin nick end labeling (TUNEL) technique.. FAS mRNA was detected in 72% of patients with PVR, 55% of patients with RD and 20% of patients with MH. TRAIL mRNA was detected in 67% of patients with PVR, 89% of patients with RD, and 20% of patients with MH. FasL mRNA was detected in 20% of patients with PVR, 9% of patients with RD, and 10% of patients with MH. The median levels of Fas and TRAIL mRNA were significantly higher (P < 0.05) in patients with PVR than in those with MH hole but between patients with PVR and those with RD the difference was not significant (P > 0.05). A significant difference was detected between RD and MH for TRAIL mRNA levels (P = 0.008). For FasL, no significant difference between groups was found. TGF-beta2 was detected in all investigated vitreous samples. A significant difference was found between the PVR and MH groups (P = 0.001) and between the RD and MH groups (P = 0.004), but not between the PVR and RD groups (P < 0.05). The level of TGF-beta2 was significantly correlated to the level of TRAIL mRNA (r = 0.86), but no correlation was found between TGF-beta2 and Fas mRNA levels (r = 0.21). Four of five examined PVR epiretinal membranes showed positive staining for apoptotic cells using the TUNEL technique.. Apoptosis is one of the mechanisms that is involved in PVR pathogenesis. Different apoptosis markers suggest different pathways occur in PVR, including Fas/FasL, TRAIL, and TGF-beta2 mediated processes.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Apoptosis Regulatory Proteins; Biomarkers; Enzyme-Linked Immunosorbent Assay; Epiretinal Membrane; Fas Ligand Protein; fas Receptor; Female; Humans; In Situ Nick-End Labeling; Male; Membrane Glycoproteins; Middle Aged; Retinal Detachment; Retinal Perforations; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; TNF-Related Apoptosis-Inducing Ligand; Transforming Growth Factor beta; Transforming Growth Factor beta2; Tumor Necrosis Factor-alpha; Up-Regulation; Vitreoretinopathy, Proliferative; Vitreous Body

Retinal pigment epithelial (RPE) cells dedifferentiate and undergo epithelial-mesenchymal transition (EMT) following retinal detachment, playing a central role in formation of fibrous tissue on the detached retina and vitreous retraction (proliferative vitreoretinopathy (PVR)). We have developed a mouse model of subretinal fibrosis with implications for PVR in which retinal detachment is induced without direct damage to the RPE cells. Transforming growth factor-beta (TGF-beta) has long been implicated both in EMT of RPEs and the development of PVR. Using mice null for Smad3, a key signaling intermediate downstream of TGF-beta and activin receptors, we show that Smad3 is essential for EMT of RPE cells induced by retinal detachment. De novo accumulation of fibrous tissue derived from multilayered RPE cells was seen following experimental retinal detachment in eyes of wild type, but not Smad3-null mice. Expression of alpha-smooth muscle actin, a hallmark of EMT in this cell type, and extracellular matrix components, lumican and collagen VI, were also not observed in eyes of Smad3-null mice. Our data show that induction of PDGF-BB by Smad3-dependent TGF-beta signaling is likely an important secondary proliferative component of the disease process. The results suggest that blocking the Smad3 pathway might be beneficial in prevention/treatment of PVR.

Topics: Actins; Animals; Becaplermin; Biomarkers; Cell Differentiation; Cell Line; Cell Movement; Chondroitin Sulfate Proteoglycans; Collagen Type VI; Disease Models, Animal; DNA-Binding Proteins; Fluorescent Antibody Technique, Indirect; Humans; Keratan Sulfate; Lumican; Mice; Mice, Inbred Strains; Mice, Knockout; Pigment Epithelium of Eye; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Retinal Detachment; Signal Transduction; Smad3 Protein; Swine; Trans-Activators; Transforming Growth Factor beta; Transforming Growth Factor beta2; Vitreoretinopathy, Proliferative

To determine whether silicone oil concentrates protein and growth factors in the retro-oil fluid.. A laboratory analysis of intraocular fluid and vitreous specimens obtained from patients undergoing removal of silicone oil, revision vitrectomy, or primary vitrectomy for macular hole, proliferative vitreoretinopathy (PVR), or retinal detachment. Patients were prospectively recruited from routine vitreoretinal operating lists. Vitreous cavity fluid and vitreous samples were analysed for the presence of transforming growth factor beta (TGF-beta2), basic fibroblast growth factor (bFGF), interleukin 6 (IL-6), and total protein using either commercially available enzyme linked immunosorbent assays (ELISA) or protein assay kits.. The median levels of bFGF, IL-6, and protein in the retro-oil fluid were raised (p<0.05) compared to all the other vitreous and vitreous cavity fluid samples. bFGF, IL-6, and protein levels were raised in PVR vitreous compared to non-PVR vitreous. TGF-beta2 levels were not significantly raised in retro-oil fluid or in PVR vitreous.. The concentration of fibrogenic (bFGF) and inflammatory (IL-6) growth factors and protein is raised in retro-silicone oil fluid. This may contribute to the process of retro-oil perisilicone proliferation and subsequent fibrocellular membrane formation.

Topics: Enzyme-Linked Immunosorbent Assay; Eye Proteins; Fibroblast Growth Factor 2; Growth Substances; Humans; Immunosuppressive Agents; Interleukin-6; Prospective Studies; Retinal Detachment; Retinal Diseases; Retinal Perforations; Silicone Oils; Transforming Growth Factor beta; Transforming Growth Factor beta2; Vitrectomy; Vitreoretinopathy, Proliferative; Vitreous Body

Transforming growth factor (TGF)-beta2 and hepatocyte growth factor (HGF) have been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR) after retinal detachment surgery. The exact role of these factors in the early events, immediately after primary retinal detachment, is not yet known, and determining their roles was therefore the purpose of this study.. Subretinal fluids were collected prospectively from 144 patients during surgery for scleral buckling. TGF-beta2 and HGF were measured with commercially available ELISA kits. Thirty patients in whom a redetachment caused by postoperative PVR developed, were compared with 114 patients with an uncomplicated retinal detachment. The controls included 18 vitreous samples from patients with macular hole or pucker. Multivariate regression analysis was used to compare the relative roles of growth factors and clinical factors in the development of PVR.. The median amount of subretinal TGF-beta2 was approximately two times lower in patients with postoperative PVR (1.9 ng/mL) than in the uncomplicated detachment group (3.3 ng/mL; P=0.002). TGF-beta2 levels in the PVR-positive group were similar to control vitreous levels (1.8 ng/mL). Subretinal HGF concentrations were not significantly different between the two groups of patients (PVR positive: 8.8 ng/mL; PVR negative: 8.9 ng/mL), but were higher than control vitreous levels (4.6 ng/mL; P=0.01). Stepwise multivariate logistic regression analysis revealed that of all factors under study, decreased TGF-beta2 content was the exclusive predictor of postoperative PVR (P=0.01).. High TGF-beta2 levels in subretinal fluid at the time of primary retinal detachment may protect a patient against subsequent development of PVR.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Fluids; Enzyme-Linked Immunosorbent Assay; Exudates and Transudates; Female; Hepatocyte Growth Factor; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Recurrence; Retinal Detachment; Scleral Buckling; Transforming Growth Factor beta; Transforming Growth Factor beta2; Vitreoretinopathy, Proliferative

We have previously shown that immunoneutralization of transforming growth factor-beta (TGF-beta) in the chick embryo significantly reduces programmed cell death (PCD) in peripheral neurons, spinal cord, and retina. In order to validate these results we have begun to analyze PCD in mice with targeted ablations of the TGF-beta2 and TGF-beta3 genes. Recent analyses of mice lacking TGF-beta3 had failed to reveal an overt eye phenotype, while retinae of TGF-beta2-deficient mice showed retinal hypercellularity. We report now that eyes of Tgfbeta2/Tgfbeta3 double-deficient mice display severe alterations in the morphology of the retina, lens, and cornea. The inner neural retina-the region where TGF-beta receptor (TbetaR) I and II immunoreactivities are most prominent-is significantly thickened, and numbers of TUNEL-positive cells are significantly reduced compared to wild-type littermates. In Tgfbeta2(-/-) Tgfbeta3(-/-) and Tgfbeta2(-/-) Tgfbeta3(+/-) littermates the retina was consistently detached from the underlying pigment epithelium. Cornea, corneal stroma, and lens epithelium were significantly thinner in these mutants. In contrast, retinal morphology in Tgfbeta2(+/-) Tgfbeta3(-/-)mutant littermates resembles the situation observed in wild-type retinae except for the retinal detachment. Thus, regression in the thickness of cornea and corneal stroma seems to be TGF-beta isoform and gene dose dependent. Our results substantiate the notion based on previous analyses of chick embryos with reduced levels of endogenous TGF-beta that TGF-beta, most notably TGF-beta2, is required to mediate PCD in developing retinal cells in vivo. Moreover, our data indicate that TGF-betas play essential roles in cornea and lens development.

Topics: Activin Receptors, Type I; Animals; Apoptosis; Cell Division; Cornea; Corneal Stroma; Crosses, Genetic; Eye; Female; Immunohistochemistry; In Situ Nick-End Labeling; Lens, Crystalline; Male; Mice; Mice, Knockout; Optic Nerve; Proliferating Cell Nuclear Antigen; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type I; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Retina; Retinal Detachment; Transforming Growth Factor beta; Transforming Growth Factor beta2; Transforming Growth Factor beta3

This study was undertaken to determine whether experimental retinal detachment produces changes in retinal localization of three isoforms of transforming growth factor beta (TGF-beta) and the type II receptor for this protein. Neural retinas of young adult cats were detached from the pigment epithelium. Survival times varied from 3 to 28 days to study the temporal course of TGF-beta localization during retinal degeneration. ELISA assay for TGF-beta1 and -beta2 was performed on samples of fluid from the vitreous chamber to determine whether active or inactive TGF-beta was present. Confocal microscopy was used to localize TGF-beta1, -beta2 and -beta3 and the type II TGF-beta receptor at the various detachment durations. Following experimental retinal detachment the levels of TGF-beta2 increased in the vitreous chamber but no changes in TGF-beta1 were detected. Levels were increased 3 days post-detachment and continued throughout the 28 day period studied. The most prominent changes in immunolocalization occurred in the TGF-beta1 and -beta2 isoforms. Increased immunolabeling was seen in Müller cells and ganglion cell bodies. Hypertrophied Müller cell processes formed periretinal membranes that were heavily labeled by the TGF-beta2 antibody. Some increased immunostaining for TGF-beta3 was observed in the ganglion cell bodies. Labeling for the TGF-beta type II receptor was seen in Müller cells, ganglion cells and the inner and outer plexiform layers in both normal and detached retinas. Changes in localization of the receptor after detachment paralleled the changes seen in TGF-beta protein localization. These results demonstrate that retinal detachment induces the synthesis and secretion of TGF-beta2. Growth factor and receptor immunolabeling were increased in Müller cells suggesting that this isoform is involved in the retinal gliotic response and may contribute to the development of proliferative vitreoretinopathy.

Topics: Animals; Blotting, Western; Cats; Enzyme-Linked Immunosorbent Assay; Microscopy, Confocal; Protein Isoforms; Receptors, Transforming Growth Factor beta; Retinal Degeneration; Retinal Detachment; Transforming Growth Factor beta; Vitreous Body

To investigate the ultrastructural distribution of platelet-derived growth factor (PDGF), transforming growth factor beta(1) (TGF-beta(1)) and their receptors in epiretinal membranes (ERM) and discuss the clinical significance of the distribution.. 25 membrane specimens were surgically removed by vitrectomy from 9 patients with rhegmatogenous retinal detachment. Double-staining techniques of immunoelectromicroscopy for eight antibodies (PDGF, TGF-beta(1), PDGF receptor subunits alpha and beta, TGF-beta subunits I and II, type I and III collagen) were used in these specimens as previously designed.. PDGF and TGF-beta(1) staining appeared to be stronger on early (< 2 months) and late (> 6 months) stage membranes than that of middle (2 - 6 months) stage of membranes, and the immunostaining intensity inverted with the degree of proliferative vitreoretinopathy (PVR). We found that the gold particles of PDGF and TGF-beta(1) tended to get together with that of type I and III collagen. In addition, the stainings of four growth factor receptors were frequently positive in a type of epithelial-like cells with rich cytoplasm components, and also the gold particles of PDGF and TGF-beta(1) were found around these cells.. A concentration change of PDGF and TGF-beta(1) exists in development of ERM throughout. The epithelial-like cells are of a type of active cells, and autocrine and paracrine activity may be involved in ERM pathogenesis. PDGF and TGF-beta(1) influence the contractile activity of ERM.

Topics: Epiretinal Membrane; Humans; Microscopy, Immunoelectron; Platelet-Derived Growth Factor; Receptors, Platelet-Derived Growth Factor; Receptors, Transforming Growth Factor beta; Retinal Detachment; Transforming Growth Factor beta; Transforming Growth Factor beta1; Vitreoretinopathy, Proliferative

Proliferative vitreoretinopathy (PVR) is a major cause of failure of retinal detachment surgery. It is believed to be a wound-healing process in the retina. Many of the cellular functions are influenced by cytokines and growth factors such as interleukins (ILs). The present study was conducted to investigate the presence of transforming growth factor-beta 2 (TGF-beta2), basic fibroblast growth factor (bFGF), IL-1beta, IL-6, and protein in the vitreous of patients with retinal detachment and to determine the value of these mediators in predicting the future development of PVR.. A prospective study was conducted in 140 consecutive patients with rhegmatogenous retinal detachment in whom vitrectomy was considered necessary. Vitreous samples were analyzed for the presence of TGF-beta2, bFGF, IL-1beta, IL-6, and protein. Patients were then followed up for 3 months for the development of postoperative PVR.. The mean levels of TGF-beta2, bFGF, IL-1beta, and protein in the vitreous were significantly higher (P < 0.05) in patients with preoperative PVR compared with those without. The mean levels of TGF-beta2, bFGF, IL-6, and protein in the vitreous were significantly higher (P < 0.05) in patients who had postoperative PVR compared with those who did not. Multivariate logistic regression analysis showed IL-6 and protein to be significant (P < 0.05), independent, predictive risk factors for the development of PVR.. The various cytokines may play a role in the pathobiology of PVR. High vitreous levels of IL-6 and protein were identified as significant risk factors for PVR. A model was developed to predict the probability of development of postoperative PVR in these patients, and it may be used to indicate intravitreal pharmacologic treatment for those at risk.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Enzyme-Linked Immunosorbent Assay; Female; Fibroblast Growth Factor 2; Humans; Interleukin-1; Interleukin-6; Male; Middle Aged; Prospective Studies; Retinal Detachment; Transforming Growth Factor beta; Vitrectomy; Vitreoretinopathy, Proliferative; Vitreous Body

Epiretinal tissue proliferations occurring during the evolution of ischemic microangiopathies or preretinal diseases are tough to cause retinal detachment by traction mechanisms. Cellular migration/proliferations and finally contraction are tough to be the pathogenic element. Myofibroblasts are contractile cells having features intermediate between those of the fibroblasts and smooth muscle. We conducted a study to explore whether such cells are present in preretinal membranes.. 8 membranes, preelevated during vitrectomy for proliferative vitreoretinopathy or diabetic proliferative vitreoretinopathy, were analysed with immunostaining technique searching for alpha-actine smooth muscle, desmine, which are specific markers for myofibroblasts and TGF-beta1, that is considered as the mean factor promoting the transformation of fibroblasts into myofibroblasts.. All the histological preparation showed abundant staining with antibody against alpha-actine smooth muscle, desmine and TGF-beta1.. Myofibroblasts are one of the major cellular element of preretinal membranes. They are scattered throughout the membrane and seem to account for their contractile properties.

Topics: Actins; Cell Division; Cell Movement; Desmin; Diabetic Retinopathy; Epiretinal Membrane; Fibroblasts; Humans; Myosins; Retinal Detachment; Transforming Growth Factor beta; Vitreoretinopathy, Proliferative

To evaluate the effect of vitrectomy and autoserum for treatment of retinal detachment caused by macular hole.. 19 eyes with retinal detachment caused by macular hole were treated with gas tamponade (C(3)F(8)). The follow-up periods ranged from 6 to 24 months. In the case whose macular hole failed to heal, removal of the remains of prefoveal membrane and/or scratching at the retinal pigment epithelium (RPE) and placing autoserum for 7 minutes in the macular hole were performed.. Closure of macular hole was obtained in 15 eyes (80%). The postoperative visual acuity was 0.05 - 0.4. Macular hole failed to heal in 4 eyes. In one eye the remains of prefoveal membrane were removed; in another 3 eyes, in the macular hole scratching at the retinal pigment epithelium (RPE) and placing autoserum were performed and C(3)F(8) tamponade was used. Anatomical cure was obtained in all the 4 eyes. The final visual acuity was 0.1 or better.. The findings show that removal of prefoveal membrane is imperative. Scratch at RPE with placement of autoserum in the macular hole is effective for the macular hole which has failed to respond to conventional vitrectomy with air tamponade.

Topics: Aged; Female; Humans; Male; Middle Aged; Postoperative Complications; Retinal Detachment; Retinal Perforations; Transforming Growth Factor beta; Transforming Growth Factor beta2; Visual Acuity; Vitrectomy

Proliferative vitreoretinopathy (PVR) is characterized by cell proliferation and membrane formation on the vitreoretinal cavity of the eye. The membranes are composed of extracellular matrix, mainly collagen type I. To explore the possible mechanisms involved in PVR membrane formation, the authors analyzed the role of vitreous humor on collagen turnover.. The authors studied vitreous samples from ten patients with PVR and from five donor eyes (keratoplasty) as the control group. Human lung fibroblasts were used to study the influence of vitreous on collagen synthesis and cell proliferation. Neutralizing antibodies against transforming growth factor-beta 2 (TGF-beta 2) were used to inhibit the fibroblast collagen synthesis induced by the vitreous samples. Collagenolytic activity was analyzed in vitreous fluid using 3H-labeled collagen.. The authors found that samples obtained from patients with PVR significantly increased collagen synthesis (2979 +/- 963.26 versus 800 +/- 232 dpm of 3H-proline incorporated per milligram of vitreous-incubated protein; P < 0.00043), without affecting fibroblast replication. The collagen synthesis induced by the vitreous samples was inhibited by anti-TGF-beta 2 antibodies in both groups (0 and 481 +/- 59 dpm of 3H-proline incorporated per milligram of vitreous-incubated protein for control and PVR samples, respectively). Collagenolytic activity was considerably lower in vitreous derived from PVR samples compared with the control group (19.9 +/- 20.3 versus 234.1 +/- 19.1 micrograms of degraded collagen per milligram of vitreous-incubated protein; P < 0.0032).. These results suggest that a combined mechanism, including an increase of collagen synthesis mediated at least in part by TGF-beta 2 and a decrease of collagen degradation, may contribute to the exaggerated deposition of collagen observed in PVR membranes, and that vitreous should be considered as a part of the microenvironment that is participating actively in the pathogenesis of this vitreoretinal disorder.

Topics: Cell Division; Collagen; Collagenases; Fibroblasts; Humans; Immunoglobulin G; Lung; Retinal Detachment; Transforming Growth Factor beta; Vitreoretinopathy, Proliferative; Vitreous Body