Biomedical subjects

O Goureau

Publications and source records attributed to O Goureau.

At least 19 recordsLinked to original sources

PubMed1998

Reduction of corneal edema in endotoxin-induced uveitis after application of L-NAME as nitric oxide synthase inhibitor in rats by iontophoresis.

PURPOSE: To investigate the involvement of the cornea during endotoxin-induced uveitis (EIU) in the rat and the effect of Ngamma-nitro-L-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor, administered by iontophoresis. METHODS: EIU was induced in Lewis rats that were killed at 8 and 16 hours after lipopolysaccharide (LPS) injection. The severity of uveitis was evaluated clinically at 16 hours, and nitrite levels were evaluated in the aqueous humor at 8 hours. Corneal thickness was measured, 16 hours after LPS injection, on histologic sections using an image analyzer. Transmission electron microscopy (TEM) was used for fine analysis of the cornea. Transcorneoscleral iontophoresis of L-NAME (100 mM) was performed either at LPS injection or at 1 and 2 hours after LPS injection. RESULTS: At 16 hours after LPS injection, mean corneal thickness was 153.7+/-5.58 microm in the group of rats injected with LPS (n=8) compared with 126.89+/-11.11 microm in the saline-injected rats (n=8) (P < 0.01). TEM showed stromal edema and signs of damage in the endothelial and epithelial layers. In the group of rats treated by three successive iontophoreses of L-NAME (n=8), corneal thickness was 125.24+/-10.36 microm compared with 146.76+/-7.52 microm in the group of rats treated with iontophoresis of saline (n=8), (P=0.015). TEM observation showed a reduction of stromal edema and a normal endothelium. Nitrite levels in the aqueous humor were significantly reduced at 8 hours by L-NAME treatment (P=0.03). No effect on corneal edema was observed after a single iontophoresis of L-NAME at LPS injection (P=0.19). Iontophoresis of saline by itself induced no change in corneal thickness nor in TEM structure analysis compared with normal rats. CONCLUSIONS: Corneal edema is observed during EIU. This edema is significantly reduced by three successive iontophoreses of L-NAME, which partially inhibited the inflammation. A role of nitric oxide in the corneal endothelium functions may explain the antiedematous effect of L-NAME.

Animals↗

PubMed1997

Inhibition of inducible nitric oxide synthase expression by interferons alpha and beta in bovine retinal pigmented epithelial cells.

Bovine retinal pigmented epithelial (RPE) cells express an inducible nitric oxide synthase (NOS-2) after activation with interferon (IFN)-gamma and lipopolysaccharide (LPS). Experiments were performed to investigate the effects of IFN-alpha and IFN-beta on NOS-2 activity. These types of interferons did not aid LPS in the production of nitrite, but markedly inhibited in a concentration-dependent manner the nitrite release due to LPS/IFN-gamma. Analysis by Western and Northern blots showed that RPE cells co-stimulated with IFN-alpha or IFN-beta with LPS/IFN-gamma accumulated lower levels of NOS-2 protein and mRNA than in the presence of LPS/IFN-gamma alone. The presence of IFN-alpha or IFN-beta did not accelerate mRNA degradation, implying that these interferons did not affect NOS-2 mRNA stability, but more probably NOS-2 gene expression. Furthermore, IFN-gamma binding studies demonstrated that the inhibitory effect of IFN-alpha and IFN-beta is not caused by a blocking of IFN-gamma receptors. Analysis of NF-kappaB activation by electrophoretic mobility shift assay demonstrated that LPS/IFN-gamma-induced NF-kappaB binding was not changed by the presence of IFN-alpha. However, similar experiments revealed that the activation of interferon regulatory factor-1 (IRF-1) by LPS/IFN-gamma was decreased by IFN-alpha. This phenomenon could be due to the decline of IRF-1 mRNA and the up-regulation of IRF-2 mRNA, an IRF-1 repressor, by IFN-alpha. These results suggest that the inhibitory effect of IFN-alpha and -beta on NOS-2 induction could be partially explained by their effect on the induction of the IRFs, which were involved in NOS-2 gene transcription.

Animals↗

PubMed1997

Control of nitric oxide production by endogenous TNF-alpha in mouse retinal pigmented epithelial and Muller glial cells.

Since the induction of nitric oxide synthase (NOS) by lipopolysaccharide (LPS) has been suggested to be partially dependent of the synthesis of tumor necrosis factor alpha (TNF alpha), we have investigated in vitro the production of NO in retinal cells from mice deficient in Lymphotoxin alpha (LT alpha)/TNF alpha. Treatment of retinal Müller glial (RMG) and retinal pigmented epithelial (RPE) cells from both wild-type and knockout mice with LPS and interferon gamma (IFN gamma) induced NO synthesis as determined by nitrite release into the media and was correlated to an increase in NOS-2 mRNA levels, evaluated by RT-PCR. However, the level of nitrite and the accumulation of mRNA was always less in cells from LT alpha/TNF alpha knockout mice than in wild type mice. Simultaneous addition of TNF alpha restored the level of NO synthesis by RMG and RPE cells from LT alpha/TNF alpha knockout mice stimulated with LPS and IFN gamma to wild type levels. Transforming growth factor beta (TGF beta) blocked LPS/IFN gamma-induced NO production is RMG and RPE cells from wild-type and LT alpha/TNF alpha knockout mice. Our results demonstrate that induction of NO synthesis in RMG and RPE cells by LPS and IFN gamma is dependent in part on endogenous TNF alpha while inhibition of NO production by TGF beta does not require a modulation of TNF alpha synthesis.

Animals↗

PubMed1997

Developmental expression of nitric oxide synthase isoform I and III in chick retina.

During our studies on the multiple possible functions of nitric oxide (NO) in chick retinal development and physiology, we have demonstrated the presence and the activity of NO synthase (NOS-I and III) in certain neuronal populations (photoreceptors, amacrine cells in the inner nuclear and ganglion cells) and also in synaptic-rich regions in the developing chick retina. Both enzymes, detected by nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, immunohistochemistry and Western blotting, appeared between embryonic days 6 and 12, and followed a spatial and temporal pattern of expression which correlated with the differentiation of the neuronal layers. Evaluation of the conversion of [3H]-labeled arginine to [3H]-citrulline, confirmed the presence of a calcium-dependent NOS activity in the cytosolic and particulate retinal extracts during the development. This pattern of NOS expression suggests that the regulated release of NO during key phases of development might be one mechanism involved in the regulation of retinal differentiation.

Animals↗

PubMed1997

Iontophoresis of dexamethasone in the treatment of endotoxin-induced-uveitis in rats.

The purpose of this study was to evaluate the efficacy of a Coulomb Controlled Iontophoresis system (CCI) in the local delivery of corticosteroids for the treatment of uveitis. The therapeutic efficacy of Dexamethasone (Dex) administered by CCI was compared to systemic injection and to topical application with the iontophoresis apparatus in the absence of electrical current. The evaluation was done in the treatment of the endotoxin-induced uveitis (EIU) model, and in the effect on TNF gene expression in the iris/ciliary body as well as in the retina and on TNF levels in aqueous humor and vitreous. Dex was administered either at the time of LPS injection or 5 hours later. For iontophoresis, we used a 1 ml reservoir-electrode covering the cornea, the limbus, and the first millimeter of the sclera. The applied electrical current was of 400 microA during four minutes with a total surface charge of 0.4 C cm-2. EIU was evaluated by clinical examination, by counts of intraocular inflammatory cells on histological sections, and by measuring the protein levels in the aqueous humor and in the vitreous. The TNF-alpha gene expression in the iris and ciliary body, and in the retina was evaluated by RT-PCR. The systemic effect of Dex delivered by CCI was evaluated on the level of serum TNF-alpha in EIU. Our results demonstrated that local administration of Dex by CCI inhibited anterior and posterior signs of intraocular inflammation as effectively as systemic administration, with no effect on systemic level of TNF. In the anterior and posterior segments of the eye, the protein exudation. TNF levels and the cellular infiltration were inhibited. The TNF-alpha gene expression was inhibited in the anterior as well as the posterior segment of the eye. No clinical nor histological damage were caused by the CCI apparatus. In conclusion, CCI administration of Dex allows for a therapeutic effect on the posterior as well as the anterior segment of the eye, and may present a viable alternative to systemic administration of glucocorticoids in severe ocular inflammations.

Animals↗

PubMed1997

Tumor necrosis factor and nitric oxide production by resident retinal glial cells from rats presenting hereditary retinal degeneration.

The inherited retinal dystrophy observed in Royal College of Surgeons (RCS) rats is a widely used model for the study of the photoreceptor degeneration that occurs in retinitis pigmentosa and macular degeneration. The visual cell degeneration is accompanied by an abnormal accumulation of microglial cells in the retina of RCS rats presenting the dystrophy. In the present study, we show that combined stimulation of RCS dystrophic retinal Müller glial (RMG) cells with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) induced the release in culture supernatants of significantly higher amounts of tumor necrosis factor (TNF) and nitric oxide (NO) compared to nondystrophic congenic controls. In contrast, the levels of TNF and NO found in the supernatants from microglial cells were not significantly different in both strains. Interestingly, as shown by thymidine incorporation, microglial cells from RCS dystrophic rats have a prominent capacity of proliferation in culture medium compared to microglia isolated from RCS non dystrophic controls. Incubation of RMG cells and microglia with the stereoselective inhibitor of NOS, NG-monomethyl-L-arginine (L-NMMA), inhibited nitrite release in LPS + IFN-gamma-stimulated RMG cells and microglia. The addition of TGF-beta with LPS + IFN-gamma clearly inhibited TNF release in supernatants from both dystrophic and control rat RMG cells and microglia. While TGF-beta significantly inhibited nitrite synthesis in RMG cells, the effect on nitrite synthesis by microglia was very low. The retinal dystrophy observed in RCS dystrophic rats could result from an abnormal reactivity of RMG and microglial cells to release TNF and NO in response to stimulants. The immunomodulatory cytokine TGF-beta and inhibitors of NOS could be negative regulators in the cytokine network and nitrite synthesis thus interfering with the development of photoreceptor cell death.

Animals↗

PubMed1997

Differential tumor necrosis factor and nitric oxide production in retinal Müller glial cells from C3H/HeN and C3H/HeJ mice.

Tumor necrosis factor (TNF) and nitric oxide (NO) have been shown to play a role in the pathogenesis of endotoxin-induced uveitis (EIU) in rats. Susceptibility to develop EIU in vivo is correlated with the extent of TNF production by retinal Müller glial cells (RMG). Moreover, RMG cells from the susceptible Lewis rat strain synthesize high amounts of nitrite under in vitro stimulation. Variations in susceptibility to endotoxin are observed among mice strains: C3H/HeN mice are known to be susceptible to develop EIU while C3H/HeJ are refractory. We show here that treatment of RMG cells from both strains with LPS + IFN-gamma does not induce TNF-synthesis in culture supernatants but produces high amounts of NO only in the supernatants from activated C3H/HeN RMG cells. The addition of TNF in the culture medium containing LPS/IFN-gamma further increases nitrite production in C3H/HeN RMG cells and allows the synthesis of low levels of nitrite in C3H/HeJ RMG cells. Addition of a specific NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), blocks NO release. We have previously shown that intraperitoneal injections of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) which inhibited nitrite and TNF release in the ocular media reduced EIU in rat. We conclude here that the in vivo susceptibility to develop EIU in mice is correlated with the extent of in vitro nitrite production by RMG cells confirming the implication of NO in the induction of ocular inflammation. The low level of retinal inflammation observed during EIU in C3H/HeN mice compared to rats could be related to the absence of TNF production by RMG cells.

Animals↗

PubMed1997

Tumor necrosis factor and nitric oxide production by retinal Müller glial cells from rats exhibiting inherited retinal dystrophy.

The primary cause of the inherited retinal dystrophy observed in Royal College of Surgeons (RCS) rats is located in the retinal pigmented epithelium, which is unable to phagocytize photoreceptor outer segments. We have demonstrated here that retinal Müller glial (RMG) cells obtained from RCS dystrophic rats and stimulated in vitro with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) accumulated higher levels of tumor necrosis factor (TNF) and inducible nitric oxide synthase (NOS II) mRNA and released in culture supernatants significantly higher amounts of TNF and nitrite compared to cells derived from nondystrophic controls. The TNF and NOS II mRNA expression and TNF and nitrite synthesis induced in RMG cells from both strains by LPS + IFN-gamma was significantly prevented by including transforming growth factor-beta (TGF-beta) in the culture medium. Coincubation of the stimulants with an inhibitor of NOS II, NG-monomethyl-L-arginine (L-NMMA), while inhibiting nitrite synthesis, induced an increase of TNF production in supernatants from RMG cells without increasing TNF mRNA levels. The retinal dystrophy observed in RCS dystrophic rats could result from an abnormal susceptibility of RMG cells form RCS dystrophic rats to produce TNF and NO in response to stimulants. Administration of the immunomodulatory cytokine TGF-beta or inhibitors of NOS II would provide additional research avenues for photoreceptor rescue.

Animals↗

PubMed1997

Expression of inducible nitric oxide synthase in bovine corneal endothelial cells and keratocytes in vitro after lipopolysaccharide and cytokines stimulation.

PURPOSE: To determine whether bovine corneal endothelial (BCE) cells and keratocytes express the inducible form of nitric oxide synthase (NOS) after exposure to cytokines and lipopolysaccharide (LPS), and to study the regulation of NOS by growth factors. METHODS: Cultures of bovine corneal endothelial cells and keratocytes were exposed to increasing concentrations of LPS, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). At selected intervals after exposure, nitrite levels in the supernatants were evaluated by the Griess reaction. Total RNA was extracted from the cell cultures, and messenger RNA levels for inducible NOS (NOS-2) were measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Exposure of BCE cells and keratocytes to LPS and IFN-gamma resulted in an increase of nitrite levels that was potentiate by the addition of TNF-alpha. Analysis by RT-PCR demonstrated that nitrite release was correlated to the expression of NOS-2 messenger RNA in BCE cells and keratocytes. Stereoselective inhibitors of NOS and cycloheximide inhibited LPS-IFN-gamma-induced nitrite release in both cells, whereas transforming growth factor-beta (TGF-beta) slightly potentiated it. Fibroblast growth factor-2 (FGF-2) inhibited LPS-IFN-gamma-induced nitrite release and NOS-2 messenger RNA accumulation in keratocytes but not in BCE cells. CONCLUSIONS: The results demonstrate that in vitro activation of keratocytes and BCE cells by LPS and cytokines induces NOS-2 expression and release of large amounts of NO. The high amounts of NO could be involved in inflammatory corneal diseases in vivo.

Animals↗

PubMed1996

Peroxynitrite cytotoxicity on bovine retinal pigmented epithelial cells in culture.

Peroxynitrite induced in vitro a dose dependent toxicity on retinal pigmented epithelial (RPE) cells. Cell death was partially mediated by apoptosis as demonstrated by nuclear fragmentation and TdT-mediated dUTP nick-end labeling assay. Peroxynitrite-induced tyrosine nitration was revealed by immunocytochemistry, both in the cytoplasm and in the nucleus of the cells. Nitration was not observed in RPE cells, producing nitric oxide (NO) after stimulation by lipopolysacharide and interferon-g (IFN-gamma), suggesting that peroxynitrite was not formed in vitro in such conditions. Peroxynitrite could be responsible for the retinal damages observed in pathological conditions in which NO has been demonstrated to be involved. In this context, EGb761, identified as a free radical scavenger, was showed herein to protect RPE cells against peroxynitrite injury.

Animals↗

PubMed1996

Recombinant IL-4 aggravates experimental autoimmune uveoretinitis in rats.

IL-4 is the critical regulatory cytokine that preferentially promotes a Th2 type of immune response. In certain models of organ-specific autoimmune diseases in which Th1 cells are implicated in the disease process, treatment with IL-4 has been shown to confer protection by deviating the immune response toward a Th2 type. In this study, we addressed the role of IL-4 in experimental autoimmune uveoretinitis, a prototypic Th1-dependent disease induced in susceptible animals following immunization with soluble retinal Ag. Interestingly, treatment of Lewis rats with IL-4 exacerbated experimental autoimmune uveoretinitis, and simultaneous treatment with neutralizing anti-IL-4 Abs attenuated this increase in the severity of the disease. Ex vivo analysis of cytokines produced in response to the immunizing Ag showed an enhancement in the levels of IFN-gamma, TNF-alpha, and nitric oxide following IL-4 treatment. In vitro, IL-4 augmented the production of IFN-gamma by Con A-stimulated splenocytes in a dose-dependent manner. At low concentrations of IL-4, IFN-gamma production was enhanced, while at higher concentrations this production was inhibited. The specificity of the induction of IFN-gamma by IL-4 was confirmed by neutralizing the activity of IL-4 with anti-IL-4. Taken together, the results herein reported demonstrate that IL-4 can induce the production of IFN-gamma and of inflammatory cytokines under certain conditions, and indicate that IL-4 can exert a dose-dependent differential effect on the induction of immune responses and on autoimmunity.

Adjuvants, Immunologic↗

PubMed1996

Accumulation of NO synthase (type-I) at the neuromuscular junctions in adult mice.

Recent data have shown that NOS-I is localized almost exclusively to the sarcolemma of fast-twitch fibers, where it probably interacts with the dystrophin-glycoprotein complex. The concentration of dystrophin-related protein at the neuromuscular junctions and the possible involvement of NO in synaptic suppression led us to investigate the presence of NOS-I at the adult motor endplates. Our data clearly show that NOS-I protein, detected by immunohistochemistry accumulates at the adult endplates. Furthermore, the absence of NOS-I protein at the denervated neuromuscular junctions suggest a neural origin of this enzyme. The putative roles of NO at the endplate are discussed.

Animals↗

PubMed1996

Expression of inducible nitric oxide synthase in the eye from endotoxin-induced uveitis rats.

PURPOSE: Inducible nitric oxide (NO) synthase (iNOS) has been implicated in the pathogenesis of endotoxin-induced uveitis (EIU). This study was undertaken to localize the cells, in the eye, which express iNOS during EIU in the rat. METHODS: EIU was induced in Lewis rats by a single foot pad injection of 150 micrograms lipopolysaccharide (LPS) from Salmonella typhimurium. At different time intervals after LPS injection, the authors evaluated ocular inflammation (slit lamp observation), iNOS localization by in situ hybridization, and comparison of OX-42- and ED1-positive cell appearance and of glial response by specific immunohistochemistry. RESULTS: iNOS mRNA was not detected in the iris-ciliary body nor in the retina of control rats. It was detected strongly in the epithelial cells of the iris-ciliary body at 6 hours and also in stromal cells of the ciliary processes at 16 hours after LPS injection. In the neuroretina, iNOS mRNA was observed in the inner layers 16 hours after LPS injection. iNOS-positive cells were also present on the vitreous at this time. At 6 and approximately 16 hours after LPS injection, immunohistochemistry experiments revealed a large number of OX-42- and ED1-positive cells (microglia, macrophages, or polymorphonuclear leukocytes) colocalized in part with some iNOS-positive cells in the ciliary body and in the retina. Furthermore, expression of iNOS in Müller cells cannot be excluded. CONCLUSIONS: These observations confirm that subcutaneous injection of endotoxin dramatically induces NOS mRNA expression in the eye, and they demonstrate that epithelial cells of the iris-ciliary body and cells infiltrating the anterior segment of the eye and the retina are the major source of NO. These results support the hypothesis that both inflammatory and resident ocular cells are involved in iNOS expression during EIU.

Animals↗

PubMed1996

Decreased intraocular pressure induced by nitric oxide donors is correlated to nitrite production in the rabbit eye.

PURPOSE: To evaluate the effect of intraocular administration of nitric oxide (NO) donors in the rabbit eye on intraocular pressure (IOP), inflammation, and toxicity. METHODS: Intravitreal and intracameral injections of two NO donors, SIN-1 and SNAP, and SIN-1C and BSS were performed. Clinical examination, IOP measurements, protein evaluation in aqueous humor, and histologic analysis of the ocular globes were realized. Nitric oxide release was demonstrated by nitrite production in the aqueous humor and in the vitreous using the Griess reaction. RESULTS: The drastic decrease of IOP, observed after a single NO donor injection, was correlated directly with nitrite production and, thus, to NO release. Injection of inactive metabolite of SIN-1, SIN-1C, which is not able to release NO, did not modulate IOP. When administered in the aqueous humor or in the vitreous, NO did not diffuse from one segment of the eye to another. No inflammation or histologic damage was observed as a result of a single NO donor administration. CONCLUSIONS: Nitric oxide is implicated directly in the regulation of IOP and its acute, and massive release into the rabbit eye did not induce inflammation or other growth toxic effects on the ocular tissues.

Acetonitriles↗

PubMed1996

[Dopamine slows phagocytosis of rods from bovine pigment epithelium in vitro trough D1 receptor].

Photoreceptor disc shedding and their phagocytosis by the retinal pigment epithelium undergo a daily rhythm entrained by an intrinsic oscillator involving melatonin and dopamine in non-mammals. Such a mechanism is not demonstrated in mammals, but the rhythm of photoreceptor renewal can be modulated by exogenous melatonin and dopamine. The present experiments were designed to show whether a direct action of DA occurs on pigment epithelial cells, and to identify the receptor mediating this action. Primary cultures of bovine retinal pigment epithelium were incubated with bovine rod outer segments in the presence of dopamine, D1 and D2 agonists, D1 antagonist and forskolin. Dopamine, D1 agonist and forskolin decreased phagocytosis, while D2 agonist was inactive. Thus dopamine slows pigment epithelium phagocytosis in vitro through a D1 receptor. Increased phagocytosis following blockade of the receptor by an antagonist suggests a more complex modulation of phagocytosis by dopamine.

Animals↗

PubMed1995

Fibroblast growth factors decrease inducible nitric oxide synthase mRNA accumulation in bovine retinal pigmented epithelial cells.

Bovine retinal pigmented epithelial cells (RPE cells), after activation with interferon gamma (IFN gamma) and lipopolysaccharide (LPS), express an inducible nitric oxide (NO) synthase. This activity can be inhibited by the fibroblast growth factors (FGF), FGF-1 (acidic FGF) and FGF-2 (basic FGF). We have attempted to elucidate the molecular mechanisms involved in the FGF inhibition of NO synthase activity. Analysis by immunocytochemistry and Western blot using a polyclonal antibody against the inducible NO synthase of rat liver reveals that RPE cells co-stimulated with FGF-2 and LPS/IFN gamma accumulate lower levels of NO synthase than in the absence of FGF-2. Northern blot analysis by cross-species hybridization with a mouse macrophage NO synthase cDNA probe shows that a 4.4-kb mRNA accumulates when RPE cells are activated with LPS/IFN gamma. The level of inducible NO synthase mRNA in LPS/IFN gamma-activated RPE cells is markedly reduced by FGF-1 or FGF-2 treatment. Message stability studies revealed that the presence of FGF did not accelerate mRNA degradation, implying that FGF did not act on inducible NO synthase mRNA stability, but more probably on its expression. Furthermore an effect of FGF on IFN gamma receptors was excluded, since IFN gamma binding was not altered by FGF. Since NO acts as a cytostatic compound, FGF, by preventing NO synthase expression in RPE cells, may protect the retina from endotoxin and cytokine-mediated tissue damage.

Amino Acid Oxidoreductases↗

PubMed1995

Increased nitric oxide production in endotoxin-induced uveitis. Reduction of uveitis by an inhibitor of nitric oxide synthase.

Nitric oxide (NO) has been implicated in the pathogenesis of several inflammatory diseases. In the present study, we investigated the potential role of NO in an ocular model of inflammation, endotoxin-induced uveitis (EIU), in Lewis rats. Injection of LPS in one footpad induces severe uveitis after 16 h, which is accompanied by an increase of NO in the aqueous and vitreous humors, as evaluated by nitrite assay. Reverse transcriptase-PCR experiments reveal a large increase of inducible NO synthase (iNOS) mRNA in the iris/ciliary body, from 2 to 24 h after LPS treatment. In the retina, maximal increase of iNOS mRNA was detected 16 h after LPS treatment. Two i.p. injections of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), which inhibits nitrite release in the aqueous and vitreous humors, profoundly reduce clinical and histologic inflammation in EIU rats. These results implicate the NO pathway in the pathogenesis of EIU and demonstrate the possibility of modulating this inflammatory disease by injection of a NOS inhibitor.

Amino Acid Oxidoreductases↗

PubMed1995

Fibroblast growth factors alter light responses and dark voltage in retinal rods of the frog (Rana temporaria).

Fibroblast growth factors (FGF-1 and FGF-2) were applied intracellularly via whole-cell patch-clamp electrodes while the membrane voltage was recorded simultaneously. During recording the exchange of substances by diffusion between cytosol and pipette medium affects the cell's function. Under control conditions, the loss of nucleotides is reflected by a slow hyperpolarization of the dark voltage and prolongated light responses. Addition of FGF-1 and FGF-2 to the pipette medium accelerated the time course of the hyperpolarization and intensified the prolongation of the light responses. The depolarization of photoreceptor cells after intracellular application of the nitric oxide (NO)-synthase cofactor nicotinamide adenine dinucleotide phosphate (NADPH) and the stabilization of light response recovery by L-arginine is abolished by FGF-2. FGF-2 was ineffective when it was applied together with the calcium chelator ethylene glycol-bis(2-aminoethylether)tetraacetate (EGTA). The results indicate a possible role of FGF in the regulation of NO and calcium in photoreceptor cells and may explain protective effects of FGF in degenerative processes of photoreceptor cells.

Amino Acid Oxidoreductases↗