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Biomedical subjects

Catherine Creuzot-Garcher

Publications and source records attributed to Catherine Creuzot-Garcher.

10 recordsLinked to original sources

Anterior chamber paracentesis in patients with acute elevation of intraocular pressure.

PURPOSE: The purpose was to evaluate the efficacy and the safety of anterior chamber paracentesis (ACP) in acute elevation of intraocular pressure (IOP). METHODS: We prospectively enrolled 20 patients who presented with acute unilateral elevation of IOP above 50 mmHg. IOP was measured before, 10 min, and 1, 7 and 30 days after ACP. The outcome at 1 year was available in 19 patients. RESULTS: The patients included 14 cases of primary acute angle-closure attacks and six cases of secondary glaucoma. IOP decreased from 53.4 +/- 4.2 mmHg to 24.1 +/- 12.5 mmHg at 10 min, to 18.2 +/- 11.1 mmHg at 24 h, and to 16.4 +/- 10.7 mmHg 7 days after ACP. ACP combined with antiglaucomatous medications provided immediate relief of symptoms in all cases and improvement of corneal oedema in 17 cases. We noted three failures in secondary glaucoma. We performed a laser peripheral iridotomy (LPI) in 14 patients and a surgical procedure in 17 eyes. No complications related to ACP were observed. CONCLUSION: ACP is a safe and effective procedure for acute elevation of IOP in acute primary primary angle-closure but only remains an add-on therapy to usual treatments. However, this technique must be evaluated in larger series.

Acute Disease↗

The retina is more susceptible than the brain and the liver to the incorporation of trans isomers of DHA in rats consuming trans isomers of alpha-linolenic acid.

Trans polyunsaturated fatty acids are formed during heat treatments of vegetable oils from polyunsaturated fatty acids containing cis double bonds. After dietary intake, they are distributed in the body and are incorporated into nervous tissues including the retina. Since nervous tissues are known to be rich in n-3 fatty acids such as docosahexaenoic acid (DHA), we studied the ability of the retina and the brain to incorporate trans isomers of DHA formed in vivo from the dietary precursor trans alpha-linolenic acid. Wistar rats were fed with trans isomers of alpha-linolenic acid for 21 months. A linear incorporation of trans DHA and a decrease in cis DHA was observed in the retina, whereas no major changes were observed in the brain. In parallel to the modifications in retinal cis and trans DHA levels, the retinal functionality evaluated by the electroretinogram showed defects in animals that consumed trans alpha-linolenic acid. These results suggest that the mechanisms leading to the incorporation of cis and trans fatty acids are quite different in the retina when compared to the brain and the liver, the retina being more susceptible to changes in the dietary lipid contribution.

Animals↗

Static postural control in children with developmental dyslexia.

The present investigation tries to better understand potential association and causal relationship between phonological and postural impairment due to developmental dyslexia. The study included 50 boys with developmental dyslexia and selected on the basis of their overall reading difficulties, and 42 control boys. Body sway during a quite standing posture eye open and eye closed on a force platform were tested in the two groups of subjects that were between 10 and 13 years of age. Analysis of classical parameters quantifying the centre of pressure (CP) displacements along antero-posterior and lateral axes showed a significant difference between the two groups. Dyslexic children showed on average greater instability, with greater length, variability and mean power frequency of CP displacements with or without vision. Our results demonstrate that postural parameters may discriminate between children with dyslexia and age-equivalent controls.

Adolescent↗

Differential mechanisms of conjunctival cell death induction by ultraviolet irradiation and benzalkonium chloride.

PURPOSE: To determine the molecular mechanisms of conjunctival cell death on exposure to the quaternary ammonium preservative benzalkonium chloride (BAC) and ultraviolet (UV) irradiation. METHODS: Chang conjunctival cells, either wild-type or stably transfected with various constructs encoding antiapoptotic molecules or transiently transfected with siRNA targeting the beclin-1 gene, were exposed to BAC or UV radiation Cell death was analyzed morphologically with fluorescence and electron microscopy, and molecular mechanisms of death were studied by using immunofluorescence, cell fractionation, caspase substrates, and immunoblot analysis, with or without immunoprecipitation. The main results were controlled in IOBA-NHC cells. RESULTS: Both agents induced cytochrome c release from the mitochondria, caspase activation, and nuclear chromatin condensation, suggesting caspase-dependent apoptosis. These events are prevented by stable expression of Bcl-2 protein. Both agents also induced a redistribution of Fas in plasma membrane rafts and the Fas-ligand-independent formation of a death-inducing complex leading to caspase-8 activation. Stable expression of either a dominant negative construct of Fas-associated death domain (FADD) or the long or short isoform of FADD-like interleukin-1-beta-converting enzyme inhibitory protein (FLIP) inhibited caspase-8 activation in response to both UV radiation and BAC. However, these proteins, as well as permeant peptides and baculovirus p35 caspase-inhibitors, delayed more efficiently the UV irradiation-induced than the BAC-induced nuclear chromatin condensation. BAC specifically activated a caspase-independent pathway by inducing the mitochondrial release of apoptosis-inducing factor. BAC-treated cells contain autophagosomes/autolysosomes, a characteristic feature of autophagy, and siRNA-mediated downregulation of the beclin-1 gene, whose product is crucial for autophagy, increases BAC toxicity. CONCLUSIONS: UV irradiation induces typical, caspase-dependent cell death, whereas death induced by BAC associates features of caspase-dependent and -independent apoptosis counteracted by an autophagic process.

Apoptosis↗

CCR 4 and CCR 5 expression in conjunctival specimens as differential markers of T(H)1/ T(H)2 in ocular surface disorders.

BACKGROUND: Accurate inflammatory mechanisms in chronic ocular surface diseases (OSDs) cannot routinely be assessed. New techniques for investigating ocular surface inflammatory pathways are of major importance. OBJECTIVE: To investigate the expressions of CCR 4 and CCR 5, known to be related to the T(H)2 and T(H)1 systems, respectively, and HLA-DR in conjunctival impression cytology specimens from patients with chronic OSDs. METHODS: In this case-controlled study, impression cytology specimens were taken in a series of patients with vernal keratoconjunctivitis (n=21), giant papillary conjunctivitis (n=6), or keratoconjunctivitis sicca (KCS; n=17), or receiving topical antiglaucoma treatments (n=31), and from 20 normal subjects. Conjunctival cells were incubated with mAbs to CCR 4, CCR 5, CD45, and HLA-DR to quantify conjunctival inflammation in a masked manner using flow cytometry. RESULTS: HLA-DR was higher in the glaucoma and KCS groups than in allergic and normal eyes. CCR 4 was overexpressed in allergy and glaucoma, whereas CCR 5 was higher in the KCS and glaucomatous groups. CD45 was expressed by only few cells in all groups, with almost no significant differences. CCR 4 expression was negatively correlated with CCR 5 and HLA-DR, whereas CCR 5 was positively correlated with HLA-DR. CONCLUSION: This study confirms the overexpression of chemokine receptors by the conjunctival epithelium in OSDs. CCR 4 and CCR 5 expression may vary according to the immune pathway involved. Accurate mechanisms in ocular surface inflammatory reactions-that is, those related to the T(H)1 or T(H)2 systems-could be differentiated by CCR 4/CCR 5 profiles. Our results also suggest that long-term use of topical treatments may stimulate both systems.

Adolescent↗

Trefoil factor family mRNA and protein expression in pterygium.

Trefoil factor family (TFF) of proteins are involved in mucosal protection and healing and are induced in inflammatory diseases and neoplastic progression. The purpose of this investigation was to determine if expression of the trefoil factor family (TFF) proteins is altered in human pterygium compared to in normal conjunctiva. Fourteen pterygia (P) and 21 biopsies from normal human conjunctiva (NC) were studied. TFF1, TFF2 and TFF3 mRNA levels were measured by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR), and TFF1 mRNA levels in addition by real-time PCR. The cellular expression of TFF1 (pS2), TFF3 (intestinal trefoil factor) and M1/MUC5AC mucin in ten pterygia and ten normal human conjunctiva specimens was analyzed by immunohistochemistry using specific monoclonal antibodies. TFF1 mRNA levels were higher in P than in NC (p=0.02). Accordingly, intensity of TFF1 and mucin MUC5AC immunostaining was higher in P than in NC. Mucus-secreting goblet cells (GC) were more densely packed in P than in NC. In both cases, TFF1 protein was detected in GC only, but was not systematically expressed in all GC. In addition, TFF3 mRNA levels were similar (p=0.89) in NC and P, while TFF2 (spasmolytic polypeptide) mRNA were not detected. Both TFF3 and MUC5AC proteins were clearly detected in all GC identified in NC and P. Increased expression of TFF1 mRNA and protein is observed in pterygium GC, suggesting that this trefoil protein might exert protective and beneficial roles during the pathogenesis of this benign and inflammatory conjunctival tumor.

Adult↗

Conjunctival epithelial cell expression of interleukins and inflammatory markers in glaucoma patients treated over the long term.

PURPOSE: To compare the conjunctival epithelial cell expressions of inflammatory cytokines in normal subjects and in glaucoma patients treated over the long term. DESIGN: Case-control study. PARTICIPANTS: A total of 69 glaucoma patients treated over the long term and 15 normal subjects with no ocular abnormality or topical treatment. METHODS: Amongst the 69 glaucoma patients, 27 were treated with preserved beta-blockers, 24 with unpreserved 0.5% timolol, and the other 18 patients with an association of > or =2 preserved drugs. All patients were treated for more than 1 year with the same treatment, with no significant differences between groups for mean ages and durations of treatment at the time of the study. Impression cytology specimens were taken and processed for immunofluorescence techniques. Conjunctival cell expressions of HLA DR, as a standard for inflammatory level, and the interleukins IL-6, IL-8, and IL-10 were obtained and quantified using flow cytometry. MAIN OUTCOME MEASURES: Immune markers and proinflammatory cytokines in impression cytology specimens. RESULTS: We found a significantly increased expression of all immunoinflammatory markers and mediators in the conjunctival epithelium of glaucoma patients compared with normal eyes. Human leukocyte antigen DR was significantly higher in the 2 groups receiving preserved drugs than in the unpreserved timolol group. The 3 interleukins were similarly overexpressed in all glaucoma groups, with no significant between-groups differences except for the expression level of IL-8, which was significantly higher in the multitreatment group than in the preservative-free one. CONCLUSIONS: The present study confirms the increased expression of immunoinflammatory markers by the conjunctival epithelium of glaucoma patients treated over the long term. The development of nontoxic preservatives or preservative-free solutions is therefore of great interest.

Adult↗

Conjunctival proinflammatory and proapoptotic effects of latanoprost and preserved and unpreserved timolol: an ex vivo and in vitro study.

PURPOSE: To compare the toxicity of latanoprost and preserved and unpreserved timolol on conjunctival cells. Expression of inflammatory markers and MUC5AC-related mucin production were evaluated by impression cytology in a case-control ex vivo study. The proapoptotic effect of the same drugs was also evaluated in vitro in a conjunctival cell line and compared with that of benzalkonium chloride (BAC). METHODS: Impression cytology (IC) specimens were obtained from a series of normal subjects and from patients with glaucoma treated for at least 1 year with latanoprost eye drops or preserved or unpreserved timolol. All groups were comparable in age and duration of treatment. Expression of HLA-DR, intercellular adhesion molecule (ICAM)-1, and mucin was evaluated in a masked manner by flow cytometry. For the in vitro study, a human conjunctiva-derived cell line was treated with 0.02% BAC-containing latanoprost or timolol, unpreserved timolol, or 0.02% BAC alone for 15 minutes, followed or not by 4 or 24 hours of cell recovery in normal medium. Cell viability and chromatin condensation were evaluated using microplate cold light cytofluorometry with the neutral red and the Hoechst 33342 tests, respectively. The Hoechst-neutral red ratio was defined for the apoptosis assay, and cytoskeleton changes were assessed by confocal microscopy. RESULTS: No difference was found between normal eyes and those receiving unpreserved timolol. Preserved latanoprost and timolol significantly increased the inflammatory marker expression and decreased MUC5AC expression, but to a significantly higher extent in the preserved timolol group compared with latanoprost. In vitro, 0.02% BAC-containing timolol and latanoprost triggered conjunctival cell apoptosis-however, to a significantly lesser extent than did 0.02% BAC alone. Unpreserved timolol did not cause any cell toxicity. CONCLUSIONS: These ex vivo and in vitro studies demonstrate that BAC-containing latanoprost and timolol exhibit higher proinflammatory and proapoptotic effects on conjunctival cells than does unpreserved timolol. Latanoprost caused less toxicity, however, than preserved timolol, and both drugs were less toxic than BAC alone. These results suggest a potential protective effect of the prostaglandin analogue and to a lesser extent of timolol against the toxicity of BAC in conjunctival cells.

Adolescent↗

Efficacy of indomethacin 0.1% and fluorometholone 0.1% on conjunctival inflammation following chronic application of antiglaucomatous drugs.

BACKGROUND: Subclinical conjunctival inflammation has been shown to have a deleterious effect on the outcome of filtering surgery. The study was designed to assess the efficacy and safety of a non-steroidal anti-inflammatory ophthalmic solution (preservative-free indomethacin 0.1%) on conjunctival inflammation following chronic application of antiglaucomatous drugs, in comparison with a steroidal ophthalmic solution (preserved fluorometholone). METHODS: Eighty-nine glaucomatous patients were included in a randomised, multicentre study comparing two parallel groups of treatment given on the basis of 1 drop 4 times daily for 1 month before filtering surgery. Patients had been treated with one or more antiglaucomatous drugs for at least 3 years. The routine antiglaucomatous treatment was continued during the study. Evaluations were carried out at baseline and after 30 days of treatment. Conjunctival inflammation was assessed under masked conditions by means of conjunctival impression analysis which determined the percentage of cells expressing HLA-DR. The ocular surface was also examined using the fluorescein test and lissamine green staining. RESULTS: Paired conjunctival impression specimens available both on day 0 (D0) and day 30 (D30) involved 49 patients. Among them, 34 eyes had a positive expression of HLA-DR at inclusion. On D30, in patients positive to HLA-DR on D0, the percentage of cells expressing HLA-DR had significantly decreased in both treatment groups: the mean reduction was 29.7% from a baseline value of 51.4% in the indomethacin group ( P=0.019) and 32.5% from a baseline value of 48.7% in the fluorometholone group ( P<0.001). There was no significant difference between groups. Seven cases of drug-related superficial punctate keratitis were observed on D30 by means of a fluorescein test: one in the indomethacin group and six in the fluorometholone group. CONCLUSION: Both anti-inflammatory eyedrops were effective in reducing subclinical conjunctival inflammation before filtering surgery. Regarding superficial punctate keratitis, the corneal tolerance of preservative-free indomethacin 0.1% eyedrops seemed to be better than that of preserved fluorometholone eyedrops.

Aged↗

Assessment of induced corneal hypoxia in diabetic patients.

PURPOSE: To assess the control of corneal hydration in patients with diabetes during a contact lens-induced hypoxia. METHODS: Corneal stress was induced in 15 patients with diabetes and 23 healthy patients by having them wear contact lenses for 2 hours. Pachymetries were measured and corneal parameters (percentage recovery per hour [PRPH], time for deswelling [T99%] and induced swelling [IS]) were calculated. In the mean time, tears were collected to assess the activity of lactate dehydrogenase (LDH), and a specular microscopy (SM) was performed. RESULTS: In patients with diabetes, PRPH, T99%, and LDH activity were statistically significantly modified (p < 0.05), whereas IS and SM were not. CONCLUSION: This decreased ability to recover the initial corneal thickness after a transient edema caused by hypoxia confirms the enzymatic dysfunction of the endothelial pumps that are partly caused by a shift toward anaerobic metabolism.

Adult↗