transforming-growth-factor-beta and Retinal-Diseases

Topics: Endothelial Growth Factors; Growth Substances; Humans; Hypoxia; Immunohistochemistry; Laser Coagulation; Retinal Diseases; Retinal Neovascularization; Transforming Growth Factor beta

Retinal neovascularization (NV) is the major cause of severe visual impairment in patients with ischemic eye diseases. While it is known that retinal microglia contribute to both physiological and pathological angiogenesis, the molecular mechanisms by which these glia regulate pathological NV have not been fully elucidated. In this study, we utilized a retinal microglia-specific Transforming Growth Factor-β (Tgfβ) receptor knock out mouse model and human iPSC-derived microglia to examine the role of Tgfβ signaling in activated microglia during retinal NV. Using a tamoxifen-inducible, microglia-specific Tgfβ receptor type 2 (Tgfβr2) knockout mouse [Tgfβr2 KO (ΔMG)] we show that Tgfβ signaling in microglia actively represses leukostasis in retinal vessels. Furthermore, we show that Tgfβ signaling represses expression of the pro-angiogenic factor, Insulin-like growth factor 1 (Igf1), independent of Vegf regulation. Using the mouse model of oxygen-induced retinopathy (OIR) we show that Tgfβ signaling in activated microglia plays a role in hypoxia-induced NV where a loss in Tgfβ signaling microglia exacerbates and prolongs retinal NV in OIR. Using human iPSC-derived microglia cells in an in vitro assay, we validate the role of Transforming Growth Factor-β1 (Tgfβ1) in regulating Igf1 expression in hypoxic conditions. Finally, we show that Tgfβ signaling in microglia is essential for microglial homeostasis and that the disruption of Tgfβ signaling in microglia exacerbates retinal NV in OIR by promoting leukostasis and Igf1 expression.

Topics: Animals; Disease Models, Animal; Hypoxia; Insulin-Like Growth Factor I; Leukostasis; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Neovascularization, Pathologic; Oxygen; Retinal Diseases; Retinal Neovascularization; Transforming Growth Factor beta

Pathological angiogenesis is driven by uncontrolled growth of endothelial cells (ECs), which could lead to retinopathy, tumor and rheumatoid arthritis, etc. ECs must experience multiple cell division process to grow, and cytokinesis is the final step. The present study shows that PEGylated GNRs (PEG-GNRs) specifically target ECs cytokinesis process which results in high ratio of binucleated cells, and these binucleated ECs lose the ability to proliferate. Further data show that PEG-GNRs do not induce toxicity in vitro and in vivo. PEG-GNRs could inhibit ECs proliferation, migration, tube formation and inhibit angiogenesis in ex vivo model. Oxygen induced retinopathy and tumor angiogenesis model further show that PEG-GNRs can inhibit angiogenesis in vivo. Gene expression profiles reveal that PEG-GNRs mainly affect ECs cell division process, and PEG-GNRs treated ECs are arrested in G2/M phase. The mechanism is that PEG-GNRs could disrupt TGFβ pathway, and subsequently suppress the assembly of actin filaments in contractile ring site. These findings indicate that PEG-GNR is a novel cytokinesis inhibitor which can be used to interfere with retinal angiogenesis and tumor.

Topics: Angiogenesis Inhibitors; Animals; Biocompatible Materials; Cell Proliferation; Cytokinesis; Endothelial Cells; Gene Expression Regulation; Gold; Humans; Male; Mice, Inbred BALB C; Mice, Nude; Nanotubes; Neovascularization, Pathologic; Oxygen; Polyethylene Glycols; Retinal Diseases; Signal Transduction; Transforming Growth Factor beta

Retinal pigment epithelium (RPE) plays an essential role in maintaining retinal function, and its defect is thought to be critically implicated in various ocular disorders. This study demonstrated that the matricellular protein CCN5 was down-regulated in ARPE-19 cells treated with the pro-fibrotic agent transforming growth factor (TGF)-β. A recombinant adenovirus expressing CCN5 (AdCCN5) was used to restore the level of CCN5 in these cells. AdCCN5 prevented TGF-β-induced fibrotic changes, including disruption of tight junctions, up-regulation of mesenchymal marker proteins, and down-regulation of epithelial marker proteins. In addition, AdCCN5 prevented TGF-β-induced functional defects, including increased migratory activity and reduced phagocytic activity. Notably, AdCCN5 reversed morphological and functional defects pre-established by TGF-β prior to viral infection. The CCN5 level was down-regulated in RPE of 18-month-old Ccl2-/- mice, which exhibited retinal defects. Restoration of the CCN5 level via intravitreal injection of a recombinant adeno-associated virus expressing CCN5 (AAV9-CCN5) normalized the altered expression of mesenchymal, epithelial, and functional marker proteins, as assessed by western blotting and immunohistochemistry. Taken together, these data suggest that down-regulation of CCN5 is associated with fibrotic deformation of RPE under pathological conditions and that restoration of the CCN5 level effectively promotes recovery of deformed RPE.

Topics: Animals; Cell Line; Dependovirus; Down-Regulation; Fibrosis; Intracellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Retinal Diseases; Retinal Pigment Epithelium; Transduction, Genetic; Transforming Growth Factor beta

Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels.. We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998.. After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR] = 1.36 per doubling of TGF-β, 95% confidence interval [CI] = 1.04, 1.78) and retinal venular diameter (1.63 μm per doubling of TGF-β, CI = 0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102 mm per doubling of PIIINP, CI = 0.029, 0.174) and impaired brachial artery reactivity (-0.20% change per doubling of PIIINP, CI = -0.39, -0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy.. Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults.

Topics: Aged; Ankle Brachial Index; Biomarkers; Brachial Artery; Carotid Artery Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Female; Fibrosis; Humans; Incidence; Male; Peptide Fragments; Peripheral Arterial Disease; Predictive Value of Tests; Procollagen; Prognosis; Prospective Studies; Retinal Diseases; Risk Factors; Transforming Growth Factor beta; United States; Vasodilation

Recent studies have shown that the retinal blood vessels are damaged in experimental models of retinal degeneration, but the mechanisms underlying their damage are not fully understood. In this study, we examined the possible role of transforming growth factor (TGF)-β in retinal neuron loss and capillary degeneration induced in rats by an intravitreal injection of N-methyl-d-aspartate (NMDA). The number of cells in the ganglion cell layer was significantly decreased 2 days after NMDA treatment, and a further decrease was observed at 7 days. Enhanced capillary degeneration was detected 7 days after NMDA treatment. Simultaneous injection of NMDA and the TGF-β inhibitor (SB431542 or LY364947) slightly but significantly attenuated the reduction in number of cells in the ganglion cell layer and almost completely prevented the enhancement of capillary degeneration. These results suggest that activation of the TGF-β signaling pathway induces neuronal and vascular cell damage in rat retina.

Topics: Animals; Benzamides; Capillaries; Dioxoles; Disease Models, Animal; Intravitreal Injections; Male; N-Methylaspartate; Pyrazoles; Pyrroles; Rats; Rats, Sprague-Dawley; Receptors, Transforming Growth Factor beta; Retinal Diseases; Retinal Ganglion Cells; Retinal Vessels; Transforming Growth Factor beta

Topics: Antiviral Agents; California; Drug Delivery Systems; Drug Design; Humans; Lactic Acid; Liposomes; Microspheres; Oligonucleotides; Peptides; Polyethylene Glycols; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Retinal Diseases; RNA, Small Interfering; Toll-Like Receptor 9; Transforming Growth Factor beta; Transforming Growth Factor beta2

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

In response to acute damage, Müller glia in the chicken retina have been shown to be a source of proliferating progenitor-like cells. The secreted factors and signaling pathways that regulate this process remain unknown. The purpose of this study was to test whether secreted factors, which are known to promote glial differentiation during development, regulate the ability of Müller glia to proliferate and become retinal progenitors in response to acute damage in mature retina. We made intraocular injections of BMP4, BMP7, EGF, NGF, BDNF, or CNTF before or after a single, toxic dose of N-methyl-d-aspartate (NMDA) and assayed for proliferating progenitor-like cells within the retina. We found that injections of BMP4, BMP7, or CNTF, but not EGF, NGF, or BDNF, before NMDA treatment reduced the number of Müller glia that proliferated and gave rise to progenitor-like cells. CNTF and BMP4, but not NGF or BDNF, greatly reduced the number of cells destroyed by toxin treatment indicating that these factors protect retinal neurons from a severe excitotoxic insult. Injections of CNTF 5 days before NMDA treatment prevented neurotoxin-induced cell death and Müller glial proliferation, while injections of BMP4 had no protective effect. In addition, CNTF injected after NMDA treatment suppressed glial proliferation, while BMP4 did not. We conclude that BMP4 and CNTF, when applied before a toxic insult, act as neuroprotective agents and likely suppress the proliferative response of Müller glia to retinal damage by attenuating the retinal damage; protecting bipolar and amacrine neurons from NMDA-induced cell death. When applied after a toxic insult, CNTF suppressed glial proliferation independent of levels of retinal damage.

Topics: Animals; Bone Morphogenetic Protein 4; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Cell Death; Cell Proliferation; Chick Embryo; Cicatrix; Ciliary Neurotrophic Factor; Gliosis; N-Methylaspartate; Nerve Degeneration; Nerve Growth Factors; Neuroglia; Neuroprotective Agents; Neurotoxins; Retina; Retinal Diseases; Transforming Growth Factor beta

Vascular endothelial growth factor (VEGF) is a major agent in choroidal and retinal neovascularization, events associated with age-related macular degeneration (AMD) and diabetic retinopathy. Retinal pigment epithelium (RPE), strategically located between retina and choroid, plays a critical role in retinal disorders. We have examined the effects of various growth factors on the expression and secretion of VEGF by human retinal pigment epithelial cell cultures (HRPE). RT-PCR analyses revealed the presence of three isoforms of mRNA corresponding to VEGF 121, 165, and 189 that were up regulated by TGF-beta1. TGF-beta1, beta2, and beta3 were the potent inducers of VEGF secretion by HRPE cells whereas bFGF, PDGF, TGF-alpha, and GM-CSF had no effects. TGF-beta receptor type II antibody significantly reversed induction of VEGF secretion by TGF-beta. In contrast activin, inhibin and BMP, members of TGF-beta super family, had no effects on VEGF expression in HRPE. VEGF mRNA levels and protein secretion induced by TGF-beta were significantly inhibited by SB203580 and U0126, inhibitors of MAP kinases, but not by staurosporine and PDTC, protein kinase C and NF-kappaB pathway inhibitors, respectively. TGF-beta also induced VEGF expression by fibroblasts derived from human choroid of eye. TGF-beta induction of VEGF secretion by RPE and choroid cells may play a significant role in choroidal neovascularization (CNV) in AMD. Since the secretion of VEGF by HRPE is regulated by MAP kinase pathways, MAP kinase inhibitors may have potential use as therapeutic agents for CNV in AMD.

Topics: Antibodies; Cells, Cultured; Choroid; Dactinomycin; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fibroblasts; Humans; MAP Kinase Signaling System; Matrix Metalloproteinases; Neovascularization, Pathologic; Pigment Epithelium of Eye; Protein Isoforms; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Retinal Diseases; RNA, Messenger; Signal Transduction; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

Experimental herpesvirus retinopathy presents a unique model of a transient inflammatory response in the virus-injected eye and subsequent acute retinal necrosis and chronic inflammation in the contralateral eye. For 6 days after infection, VEGF, TGFbeta1, and TGFbeta2 were associated only with inflammatory cells in the injected eye. By 6 days (after viral antigens were no longer detected), VEGF and TGFbeta2 were upregulated in retinas of injected eyes until 8-10 days. In contralateral eyes, VEGF was first demonstrated in the retina at 6-7 days (prior to the appearance of viral antigens) and TGFbeta2 at 7-8 days. Staining for these factors was also evident around areas of necrosis. The VEGF receptor, flt-1, was associated with ganglion cells and the inner nuclear layer of normal and experimental mice and it was also demonstrated around areas of necrosis. Another VEGF receptor, flk-1, was localized to Muller cell processes and the outer plexiform layer in normal and experimental mice. Coincident with VEGF upregulation in the retinas of herpesvirus-1 injected mice, there was increased flk-1 in ganglion cells and the inner and outer nuclear layers. IL-6 was associated with Muller cell endfeet in normal mice. Following unilateral intraocular inoculation, IL-6 spread along the MUller cell processes and some astrocytes demonstrated IL-6 in both eyes at 6-8 days. The present study demonstrates that intraocular inoculation of herpesvirus is sufficient to induce VEGF, flk-1, TGFbeta2, and IL-6 in the retinas of injected and contralateral eyes. Further investigation of common signaling pathways for these factors during responses to viral infection and the development of acute retinal necrosis could provide information useful for therapeutic intervention in human herpesvirus retinopathy.

Topics: Animals; Endothelial Growth Factors; Extracellular Matrix Proteins; Herpesviridae Infections; Immunohistochemistry; Inflammation; Interleukin-6; Lymphokines; Mice; Mice, Inbred BALB C; Myosin Heavy Chains; Nonmuscle Myosin Type IIB; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; Retina; Retinal Diseases; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors

An increased expression and secretion of angiogenic growth factors was proposed to occur in proliferative diabetic retinopathy and other neovascularizing retinal diseases. However, a loss of anti-angiogenic factors also might promote retinal neovascularization. Therefore we investigated the active and latent vitreous levels of the subtypes of the endothelial anti-mitogen transforming growth factor-beta in vitreous of 58 patients. Four groups of patients were compared: Controls without retinal hypoxia, patients with quiescent and active proliferative diabetic retinopathy (PDR), and patients with severe retinal hypoxia resulting in rubeosis iridis. Whereas the amount of total TGF-beta in the four groups did not differ significantly, latent TGF-beta isoform expression showed complex alterations in ocular vitreous. Levels of active TGF-beta of patients with active PDR (79.5 +/- 28 pg/ml; n = 8) were decreased to 20% of the control levels (378 +/- 55 pg/ml; n = 12; p = 0.0005) and 25% of the mean concentration in quiescent PDR (346 +/- 64 pg/ml; n = 9; p = 0.0021). Levels in rubeosis (52 +/- 10 pg/ml; n = 10) did not differ significantly from those found in active PDR but were decreased to 15% of those in patients with quiescent PDR (p = 0.0004). Furthermore a highly significant inverse correlation between active TGF-beta and alpha2-antiplasmin, a liver produced inhibitor of the activation of TGF-beta by plasmin was noted (r = -0.59; n = 28; p = 0.001). We conclude that deficient activation of TGF-beta occurs in active proliferative diabetic retinopathy and in hypoxic angiogenesis most likely as a consequence of a blood retina barrier breakdown and influx of alpha2-antiplasmin from serum. The disinhibition of endothelial cell proliferation may be a central component in the process of neovascularization.

Topics: Aged; alpha-Macroglobulins; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Eye; Female; Fibrinolysin; Humans; Male; Middle Aged; Neovascularization, Pathologic; Retinal Diseases; Transforming Growth Factor beta; Vitreous Body

The targeted induction of apoptosis is a novel therapeutic approach to control the unlimited growth of proliferating cells. Since massive proliferation of cells at the vitreoretinal interface is a key feature of proliferative vitreoretinal disorders, we sought to identify apoptosis in epiretinal membranes from patients with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR) and macular pucker. Further, we evaluated the possible induction of apoptosis of retinal pigment epithelial (RPE) cells by transforming growth factor-beta(TGF-beta). Apoptotic cells were identified by in situ DNA end labeling and acridine orange staining on paraffin-embedded tissue sections from epiretinal membranes of patients with all vitreoretinal disorders examined. Labeled nuclei or condensed chromatin were scattered throughout the membranes or occurred in clusters. Most apoptotic cells were RPE-derived, as assessed by cytokeratin immunochemistry. No apoptotic glial cells were detected. In PVR, proliferative activity, as confirmed by Ki-67 immunochemistry, was associated with short history and rapid disease progression. Apoptotic nuclei were observed more frequently in long-standing PVR or slow progression towards traction retinal detachment. TGF-beta was detected in all control vitreous samples by bioassay at concentrations below 20 ng ml-1. TGF-beta levels increased up to 20-fold in pathological vitreous. Marked heterogeneity was observed in all patient groups. The degree of TGF-beta activation was significantly higher in PVR than in PDR. Proapoptotic effects of TGF-beta were demonstrated in cultured human RPE cells by electron microscopy, in situ DNA end labeling, comet assay and a photometric enzyme immunoassay for histone-associated DNA fragments. Apoptosis appears to be a key regulatory mechanism of growth control of specific cell populations in proliferative vitreoretinal disorders. Administration of proapoptotic growth factors such as TGF-beta may provide a novel approach to inhibit cellular proliferation at the vitreoretinal interface.

Topics: Apoptosis; Cells, Cultured; Diabetic Retinopathy; Humans; Immunohistochemistry; Ki-67 Antigen; Pigment Epithelium of Eye; Retinal Diseases; Transforming Growth Factor beta; Vitreous Body

To establish and quantify the presence of contraction-stimulating activity in pathologic vitreous and correlate this activity with clinical presentation and outcome, especially with proliferative vitreoretinopathy.. Contraction-stimulating activity of vitreous collected during surgery was quantified with a tissue culture assay using fibroblasts as target cells. The activity of each sample was correlated with patient history, clinical presentation, risk factors, proliferative disease, and postoperative proliferation.. Pathologic vitreous contained measurable quantities of contraction-stimulating activity and stimulated contraction in vitro, with elevated activities in samples from patients with proliferative vitreoretinopathy, epimacular proliferation, retinal detachment, retinal defects, pigmented cells in the vitreous, hemorrhage, or uveitis. Patients with postoperative proliferation had significantly elevated mean activities.. Levels of contraction-stimulating activity in pathologic vitreous correlate with some risk factors for the development of proliferative vitreoretinopathy and may ultimately be useful in the assessment of disease severity and the prediction of postoperative proliferation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biological Factors; Cell Division; Cells, Cultured; Child; Collagen; Female; Fibroblasts; Humans; Male; Middle Aged; Retinal Diseases; Skin; Transforming Growth Factor beta; Vitrectomy; Vitreoretinopathy, Proliferative; Vitreous Body

The main cause of failure after retinal reattachment surgery is proliferative vitreoretinopathy (PVR), in which contractile fibrocellular membranes form on the retinal surface and vitreous base. Recently, elevated levels of transforming growth factor-beta 2 (TGF-beta 2) were measured in the vitreous of patients with PVR, suggesting a possible association with the disease. Because neutralizing TGF-beta may prove useful in controlling this blinding disease process, the authors examined the effect of anti-TGF-beta 1 and TGF-beta 2 antibodies in TGF-beta-mediated fibroblast-induced collagen gel contraction.. Rabbit dermal fibroblasts were combined with type I collagen in an in vitro model of collagen gel contraction. The authors evaluated the effect of TGF-beta 1, TGF-beta 2, and their antibodies on fibroblast-induced gel contraction.. TGF-beta 1 and TGF-beta 2 equally enhanced gel contraction to an average of 6% to 7% of the control area by day 4. In contrast, gels without TGF-beta contracted only to an average of 38% of the control gels. Several anti-TGF-beta antibodies neutralized this TGF-beta-enhanced contraction, whereas control IgGs had no effect. A dose-dependent response was detected with TGF-beta 1, TGF-beta 2, and anti-TGF-beta.. Because TGF-beta levels have been shown to correlate with the severity of PVR, the neutralizing action of anti-TGF-beta on TGF-beta-mediated contraction may offer further insights into the structure and function of PVR membranes and may provide clues to possible therapeutic solutions for controlling this disease process.

Topics: Animals; Antibodies; Cells, Cultured; Collagen; Eye Diseases; Fibroblasts; Gels; Models, Biological; Neutralization Tests; Rabbits; Retinal Diseases; Transforming Growth Factor beta; Vitreous Body

Proliferative vitreoretinopathy (PVR) involves the formation of intravitreal fibrocellular membranes which may lead to traction retinal detachment and blindness. The cellular component of epiretinal membranes originates from the proliferation and migration of cells within the eye. Several growth factors and other cytokines are plausible candidates for directing the processes leading to membrane formation. A reproducible animal model is needed for experimental studies of cytokine expression during PVR induction or treatment. We found that intravitreal injection of > 10(6) mixed mononuclear leukocytes or adherent monocytes along with a trans-scleral incision through the pars plana leads to the development of PVR-like disease in rabbit eyes. The severity of the disease was related to the number of monocytes injected. Typically, organized membranes extending from the incision toward the optic nerve formed within one week. Progression to extensive traction retinal detachment required 1 to 4 weeks. Injection of up to 5 x 10(6) lymphocytes or freeze-thaw killed monocytes was ineffective, and coinjecting 100 micrograms endotoxin with the monocytes did not result in enhanced disease. The histological appearance of the epiretinal membranes was similar to human PVR membranes. Macrophage, cytokeratin-positive (epithelial), and fibroblast-like cells were present. Northern blot analysis of RNA extracted from the rabbit membranes revealed the presence of mRNA for acidic fibroblast growth factor (aFGF). Acidic FGF mRNA was not expressed by the injected monocytes. A comparable level of aFGF mRNA and also mRNAs for basic FGF, platelet-derived growth factor-B, and transforming growth factor beta were found in epiretinal membranes induced by a scleral incision in association with cryopexy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Disease Models, Animal; Eye Diseases; Fibroblast Growth Factor 1; Fibroblast Growth Factor 2; Growth Substances; Monocytes; Platelet-Derived Growth Factor; Rabbits; Retinal Diseases; RNA; RNA, Messenger; Transforming Growth Factor beta; Vitreous Body