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W Rostène

Publications and source records attributed to W Rostène.

At least 19 recordsLinked to original sources
PubMed2002

Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain.

Recent studies demonstrated that the chemokine monocyte chemoattractant protein-1 (MCP-1)/CCL2 and its receptor, CCR2, play important roles in various brain diseases. In this study, using quantitative autoradiography, we studied the pharmacological properties of [125l]MCP-1/CCL2 binding in rat brain and we clearly showed the distribution of CCR2 receptors in cerebral cortex, nucleus accumbens, striatum, amygdala, thalamus, hypothalamus, hippocampus, substantia nigra, mammillary bodies and raphe nuclei. Moreover, using double fluorescent immunohistochemistry, we showed that CCR2 receptors were constitutively expressed on neurons and astrocytes. Using RT-PCR methods, we demonstrated that CCR2 mRNA is present in various brain areas described above. Four hours after an acute intraperitoneal lipopolysaccharide injection, we showed that MCP-1/CCL2 binding was up-regulated in several brain structures; this effect took place on both CCR2B labelled neurons and astrocytes and to a lesser extent on activated microglia. To explore neurobiological function of CCR2, actimetric study was carried out. After intracerebroventricular injections of MCP-1/CCL2, we showed that motor activity was markedly decreased. Our results provide the first evidence for constitutive CCR2 receptor expression with precise neuroanatomical and cellular localizations in the brain, and its regulation during an inflammatory process, suggesting that MCP-1/CCL2 and CCR2 play important physiological and pathophysiological role(s) in the CNS.

Animals↗
PubMed2001

Baicalein protects cortical neurons from beta-amyloid (25-35) induced toxicity.

Accumulation of amyloid beta peptide (Abeta) has been suggested to contribute to neurodegeneration in Alzheimer's disease (AD). Since chronic inflammation occurs in AD pathogenesis and lipoxygenases are important mediators of inflammatory processes, we evaluated the effect of lipoxygenase inhibitors on apoptosis induced by Abeta on rat cortical cells. The 12-lipoxygenase inhibitor baicalein attenuated both neuronal apoptosis and c-jun protein over-expression induced by Abeta(25- 35), whereas no protection was found with the broad spectrum lipoxygenase inhibitor nordihydroguaiaretic acid or the 5-lipoxygenase inhibitor caffeic acid. These results suggest that 12-lipoxygenase participates in a c-jun-dependent apoptosis pathway triggered by Abeta(25-35), and that specific 12-lipoxygenase inhibitors might be of interest in AD.

Amyloid beta-Peptides↗
PubMed2001

Neurotensin gene expression and behavioral responses following administration of psychostimulants and antipsychotic drugs in dopamine D(3) receptor deficient mice.

Exposure to psychostimulants and antipsychotics increases neurotensin (NT) gene expression in the striatum and nucleus accumbens. To investigate the contribution of D(3) receptors to these effects we used mice with targeted disruption of the D(3) receptor gene. Basal NT mRNA expression was similar in D(3) receptor mutant mice and wild-type animals. Acute administration of haloperidol increased NT gene expression in the striatum in D(3)+/+, D(3)+/- and D(3)-/- mice. Similarly, acute cocaine and amphetamine induced NT mRNA expression in the nucleus accumbens shell and olfactory tubercle to a comparable extent in D(3) mutants and wild-type mice. Daily injection of cocaine for seven days increased NT mRNA in a restricted population of neurons in the dorsomedial caudal striatum of D(3)+/+ mice, but not in D(3)-/- and D(3)+/- animals. No differences were observed between D(3) receptor mutant mice and wild-type littermates in the locomotor activity and stereotyped behaviors induced by repeated cocaine administration. These findings demonstrate that dopamine D(3) receptors are not necessary for the acute NT mRNA response to drugs of abuse and antipsychotics but appear to play a role in the regulation of NT gene induction in striatal neurons after repeated cocaine. In addition, our results indicate that the acute locomotor response to cocaine and development of psychostimulant-induced behavioral sensitization do not require functional D(3) receptors.

Amphetamine↗
PubMed2001

Transcriptional regulation of the tyrosine hydroxylase gene by neurotensin in human neuroblastoma CHP212 cells.

The human neuroblastoma cell line CHP212 was found to express functional high affinity neurotensin (NTS-1) receptor subtype. Based on the functional interactions between neurotensin and dopamine transmission, we have used this cell line to investigate the short- and long-term modulation of tyrosine hydroxylase gene expression by the stable neurotensin agonist JMV 449. After exposure of the cells to 1 microM JMV 449 for 5 or 72 h, tyrosine hydroxylase protein and mRNA levels were significantly increased as detected by western blot analysis and quantitative RT-PCR, respectively. Transfection of CHP212 cells with a plasmid containing the luciferase reporter gene under the control of a limited proximal region of the cloned tyrosine hydroxylase promoter, revealed that the effect of JMV 449 results from an increase in the transcriptional activity of the TH gene. These results indicate that modulation of tyrosine hydroxylase gene expression may constitute one of the mechanisms involved in the control of dopamine transmission by neurotensin. Such neurotensin-mediated changes in tyrosine hydroxylase expression may also participate in multiple adaptation processes within the central nervous system to environmental conditions where neurotensin is released such as stress and food intake.

Blotting, Western↗
PubMed2001

Resistance to induced apoptosis in the human neuroblastoma cell line SK-N-SH in relation to neuronal differentiation. Role of Bcl-2 protein family.

Much evidence suggests that apoptosis plays a crucial role in cell population homeostasis that depends on the expression of various genes implicated in the control of cell life and death. The sensitivity of human neuroblastoma cells SK-N-SH to undergo apoptosis induced by thapsigargin was examined. SK-N-SH were previously differentiated into neuronal cells by treatments with retinoic acid (RA), 4 beta-phorbol 12-myristate 13-acetate (PMA) which increases protein kinase C (PKC) activity, and staurosporine which decreases PKC activity. Neuronal differentiation was evaluated by gamma-enolase, microtubule associated protein 2 (MAP2) and synaptophysin immunocytochemistry. The sensitivity of the cells to thapsigargin-induced apoptosis was evaluated by cell viability and nuclear fragmentation (Hoechst 33258) and compared with pro-(Bcl-2, Bcl-x(L)) and anti-apoptotic (Bax, Bak) protein expression of the Bcl-2 family. Cells treated with RA and PMA were more resistant to apoptosis than controls. Conversely, the cells treated with staurosporine were more susceptible to apoptosis. In parallel with morphological modifications, the expression of inhibitors and activators of apoptosis was directly dependent upon the differentiating agent used. Bcl-2 expression was strongly increased by PMA and drastically decreased by staurosporine as was Bcl-x(L) expression. Bax and Bak expression were not significantly modified. These results demonstrate that drugs that modulate PKC activity may induce a modification of Bcl-2 expression as well as resistance to the apoptotic process. Furthermore, the expression of Bcl-2 was reduced by toxin B from Clostridium difficile and, to a lesser extent, by wortmannin suggesting a role of small G-protein RhoA and PtdIns3 kinase in the control of Bcl-2 expression. Our data demonstrate a relationship between the continuous activation of PKC, the expression of Bcl-2 protein family and the resistance of differentiated SK-N-SH to apoptosis.

Androstadienes↗
PubMed2001

Increased plasma neurotensin concentrations in patients with Parkinson's disease.

Plasma neurotensin (NT) was measured by radioimmunoassay in propanol extracted and unextracted plasma from 16 parkinsonian patients (four before treatment) and 16 age and sex matched controls. Mean plasma NT concentrations were consistently higher in parkinsonian patients than in controls and higher in the four untreated patients than in levodopa treated patients suggesting that plasma NT measurement may represent an easy detectable additional index in diagnosing parkinsonism and provides a novel approach to research in this field.

Aged↗
PubMed2000

Characterization and visualization of [125I] stromal cell-derived factor-1alpha binding to CXCR4 receptors in rat brain and human neuroblastoma cells.

Stromal cell-Derived Factor-1 (SDF-1alpha), binds to the seven-transmembrane G protein-coupled CXCR4 receptor and modulates cell migration, differentiation, and proliferation. CXCR4 has been reported to be expressed in various tissues including brain. Moreover, CXCR4 has recently been shown to be one of the coreceptors for HIV-1 infection which could be implicated in HIV encephalitis. In the present study, the binding properties and autoradiographic distribution of [125I]SDF-1alpha binding to CXCR4 were characterized in the adult rat brain. SDF-1alpha binding and CXCR4 coupling system were also studied in human neuroblastoma cell line SK-N-SH. The binding of [125I]SDF-1alpha on rat brain sections was specific, time-dependent and reversible. The highest densities of CXCR4 were detected in the choroid plexus of the lateral and the dorsal third ventricle. Lower densities of [125I]SDF-1alpha binding sites were observed in various brain regions including cerebral cortex, anterior olfactory nuclei, hippocampal formation, thalamic nuclei, blood vessels and pituitary gland. In the choroid plexus, the IC(50) and K(d) of [125I]SDF-1alpha binding were respectively 0.6 nM and 0. 36 nM. Similar IC(50) values were obtained in other brain structures. A CXCR4 antagonist, bicyclam, competed with SDF-1alpha binding (30% inhibition at 10(-6) M). In SK-N-SH cells, [125I]SDF-1alpha bound to CXCR4 with a K(d) of 5.0 nM and a maximal binding capacity of 460 fmol/mg of protein. SDF-1alpha induced a rapid and transient intracellular calcium increase in SK-N-SH cells. These findings suggest that CXCR4 is highly expressed in some brain structures and have a regulatory role in the nervous system. The significance of this expression in the brain parenchyma and more specifically in the choroid plexus remains to be clarified in the normal as well as in the infected brain.

Animals↗
PubMed2000

Immunologic differentiation of two high-affinity neurotensin receptor isoforms in the developing rat brain.

Earlier studies have demonstrated overexpression of NT1 neurotensin receptors in rat brain during the first 2 weeks of life. To gain insight into this phenomenon, we investigated the identity and distribution of NT1 receptor proteins in the brain of 10-day-old rats by using two different NT1 antibodies: one (Abi3) directed against the third intracellular loop and the other (Abi4) against the C-terminus of the receptor. Immunoblot experiments that used Abi3 revealed the presence of two differentially glycosylated forms of the NT1 receptor in developing rat brain: one migrating at 54 and the other at 52 kDa. Whereas the 54-kDa form was expressed from birth to adulthood, the 52-kDa form was detected only at 10 and 15 days postnatal. Only the 52-kDa isoform was recognized by Abi4. By immunohistochemistry, both forms of the receptor were found to be predominantly expressed in cerebral cortex and dorsal hippocampus, in keeping with earlier radioligand binding and in situ hybridization data. However, whereas Abi4 immunoreactivity was mainly concentrated within nerve cell bodies and extensively colocalized with the Golgi marker alpha-mannosidase II, Abi3 immunoreactivity was predominantly located along neuronal processes. These results suggest that the transitorily expressed 52-kDa protein corresponds to an immature, incompletely glycosylated and largely intracellular form of the NT1 receptor and that the 54-kDa protein corresponds to a mature, fully glycosylated, and largely membrane-associated form. They also indicate that antibodies directed against different sequences of G-protein-coupled receptors may yield isoform-specific immunohistochemical labeling patterns in mammalian brain. Finally, the selective expression of the short form of the NT1 receptor early in development suggests that it may play a specific role in the establishment of neuronal circuitry.

Animals↗
PubMed2000

Regulation of the neurotensin NT(1) receptor in the developing rat brain following chronic treatment with the antagonist SR 48692.

The aim of the present study was to investigate the role of neurotensin in the regulation of NT(1) receptors during postnatal development in the rat brain. Characterization of the ontogeny of neurotensin concentration and [(125)I]neurotensin binding to NT(1) receptors in the brain at different embryonic and postnatal stages showed that neurotensin was highly expressed at birth, reaching peak levels at postnatal day 5 (P5) and decreasing thereafter. The transient rise in neurotensin levels preceded the maximal expression of NT(1) receptors, observed at P10, suggesting that neurotensin may influence the developmental profile of NT(1) receptors. Using primary cultures of cerebral cortex neurons from fetal rats, we showed that exposure to the neurotensin agonist JMV 449 (1 nM) decreased (-43%) the amount of NT(1) receptor mRNA measured by reverse transcription-PCR, an effect that was abolished by the nonpeptide NT(1) receptor antagonist SR 48692 (1 microM). However, daily injection of SR 48692 to rat pups from birth for 5, 9, or 15 days did not modify [(125)I]neurotensin binding in brain membrane homogenates. Moreover, postnatal blockade of neurotensin transmission did not alter the density and distribution of NT(1) receptors assessed by quantitative autoradiography nor NT(1) receptor mRNA expression measured by in situ hybridization in the cerebral cortex, caudate-putamen, and midbrain. These results suggest that although NT(1) receptor expression can be regulated in vitro by the agonist at an early developmental stage, neurotensin is not a major factor in the establishment of the ontogenetic pattern of NT receptors in the rat brain.

Animals↗
PubMed2000

Role of dopamine D3 receptors in thermoregulation: a reappraisal.

Dopamine agonist-induced hypothermia has been proposed to be mediated by the D3 receptor (D3R), as it is elicited by (+)7-OH-DPAT and antagonized by S 14297, two putative D3R-preferential ligands. Here we show, however, that S 14297 is a full and partial agonist at D3R and D2R, respectively. Hypothermia was induced in rats by agonists with potencies correlated with their D3R and D2R functional potencies, and was reversed by antagonists, with a rank order of potency typical of the D2R. Moreover, BP 897, a highly potent and selective but partial D3R agonist was inactive in producing hypothermia or reversing (+)7-OH-DPAT-induced hypothermia. (+)7-OH-DPAT was as potent and efficient in inducing hypothermia in wild-type as in D3R-deficient mice. Hence, our results suggest that hypothermia does not result from a selective stimulation of the D3R.

2-Naphthylamine↗
PubMed2000

Automated keratoconus detection using the EyeSys videokeratoscope.

PURPOSE: To evaluate the effectiveness of indices derived from the EyeSys System 2000 in detecting keratoconic corneas. SETTING: Department of Ophthalmology, Hôpital Saint Antoine, Paris VI University, Paris, France. METHODS: Topographies of 208 corneas were evaluated. The corneas were from 8 groups of patients classified by the following diagnoses: normal, regular astigmatism, cataract, radial keratotomy, photorefractive keratectomy, myopic keratomileusis, penetrating keratoplasty (PKP), and keratoconus. Nine statistical indices derived from EyeSys data, 2 Holladay Diagnosis Summary indices (coefficient of uniformity and coefficient of asphericity [Asph]), and our refractive power symmetry index were studied. A training set of 104 corneas was used to determine the most efficient threshold value of each index based on sensitivity and specificity curves. Decision trees combining 2 indices were generated. Sensitivity and specificity were calculated in a validation set composed of the remaining 104 corneas. RESULTS: Based on the results of the training set, the optimum indices were SDSD (standard deviation of the standard deviations of the radii of curvature of each ring) and Asph. In the validation set, the decision tree using these indices featured 88.5% sensitivity and 94.9% specificity; the 4 false-positive cases were in corneas in the PKP group of patients. CONCLUSIONS: Clinically apparent keratoconus can be detected among normal corneas and irregular corneal shape patterns using the EyeSys System 2000 data and a decision tree combining 2 indices.

Astigmatism↗
PubMed2000

Tibolone actions on normal and breast cancer cells.

Tibolone and its main derivatives were studied in an original model of cultures of normal human epithelial breast (HBE) cells on proliferation, differentiation and apoptosis, the three mechanisms responsible for breast homeostasis. Tibolone and its Delta4 isomer were antiproliferative, both in the absence and presence of oestradiol (E2). The oestrogenic 3alpha and 3beta hydroxy derivatives did not display any mitogenic activities in HBE cells. Moreover, at 1 microM, they were antiproliferative. Tibolone and its Delta isomer increased the 17beta hydroxysteroid dehydrogenase activity similarly to that observed with progestins [1]. Apoptosis was increased in HBE cells to a similar range as with the pure pregnane progestin, Org2058. We also studied the extent of apoptosis in hormone-dependent breast cancer cell lines. Tibolone and its Delta4 isomer also increased apoptosis, especially in ZR75-1 cells containing progesterone and androgen receptors [2]. We could demonstrate that these pro-apoptotic actions of tibolone and its Delta4 isomer were mediated at least partially through the bcl-2-family of proteins. Moreover, the antiproliferative and pro-apoptotic activities of tibolone, as well as Org2058, were mediated by increasing catalase activities in breast cancer cells. Thus, in breast cells, tibolone slows down the proliferation rate, increases differentiation and apoptosis. These actions seem to be optimal on breast tissue.

Antineoplastic Agents, Hormonal↗
PubMed2000

Successful surgical removal of occult metastases of medullary thyroid carcinoma recurrences with the help of immunoscintigraphy and radioimmunoguided surgery.

Patients with recurrent or metastatic medullary thyroid carcinoma (MTC) were referred for pretargeted immunoscintigraphy (Affinity Enhancement System; AES) and radioimmunoguided surgery (RIGS). Data collected from 13 patients establish that whole-body AES immunoscintigraphy revealed metastases < 360 mg and RIGS detected micrometastases (5-15 mg). All tissue samples removed by the surgeon were diagnosed by histology and immunohistochemistry of calcitonin to check the accuracy of IS and RIGS results. AES immunoscintigraphy is very sensitive. Of 34 metastases or recurrences detected, 22 had escaped physical examination or conventional imaging. The accuracy of RIGS was 86%, its sensitivity 75%, and its specificity was 90% (n = 208). IS and RIGS detected occult tumors that would have escaped surgery, clearly demonstrating clinical benefit. Serum calcitonin (normal, 10 pg/ml) and carcinoembryonic antigen (normal, 5 ng/ml) of two patients were restored to normal. In patients whose tumors were discovered, progression of their disease was slowed, as evidenced by the large decrease in serum calcitonin and carcinoembryonic antigen, an important prognostic factor. Surgery was canceled in one case where IS detected distant metastases out of surgical reach. Thus, AES immunoscintigraphy and RIGS might be of valuable help for the surgical management of medullary thyroid carcinoma.

Adult↗
PubMed2000

Regulation of human corneal epithelial cell proliferation and apoptosis by dexamethasone.

PURPOSE: To investigate whether human corneal epithelial cells express the glucocorticoid receptor (GR) and to assess the influence of dexamethasone (DEX) on these cells. METHODS: Human corneal epithelial cells were cultured in medium supplemented with various concentrations of DEX (ranging from 10(-10) to 10(-4) M). Cell proliferation was analyzed by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfop henyl) -2H-tetrazolium inner salt (MTS) assay at 2, 4, and 6 days of culture. Apoptosis was studied by nucleus labeling using a fluorescent dye and immunostaining by APO 2.7 at 6 days of culture. GR mRNA was detected in corneal epithelium and cultured corneal epithelial cells by means of reverse transcription-polymerase chain reaction (RT-PCR). Immunocytochemical staining of the epithelial cells was performed with a monoclonal anti-human GR. RESULTS: RT-PCR and immunocytochemistry showed the expression of GR (mRNA and protein) in corneal epithelial cells. DEX significantly increased corneal epithelial cell proliferation with concentrations ranging from 10(-10) to 10(-6) M, with a maximum effect at 10(-7) M (P < 0.005). However, DEX also induced apoptosis of cultured corneal epithelial cells at any concentration used. CONCLUSIONS: These results indicate that human corneal epithelial cells express the GR and proliferate in response to DEX stimulation which also induces corneal epithelial cell apoptosis.

Apoptosis↗
PubMed1999

Neurotensin receptors and dopamine transporters: effects of MPTP lesioning and chronic dopaminergic treatments in monkeys.

The effect of denervation with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of the dopamine (DA) nigrostriatal pathway on neurotensin (NT) receptor and DA transporter (DAT) in basal ganglia of monkeys (Macaca fascicularis) was investigated. The MPTP lesion induced a marked depletion of DA (90% or more vs. control) in the caudate nucleus and putamen. The densities of NT agonist binding sites labeled with [125I]NT and the NT antagonist binding sites labeled with [3H]SR142948A decreased by half in the caudate-putamen of MPTP-monkeys. In addition, the densities of [125I]NT and [3H]SR142948A binding sites markedly decreased (-77 and -63%, respectively) in the substantia nigra of MPTP-monkeys. Levocabastine did not compete with high affinity for [125I]NT binding in the monkey cingulate cortex, suggesting that only one class of NT receptors was labelled in the monkey brain. An extensive decrease of [3H]GBR12935 DAT binding sites (-92% vs. Control) was observed in the striatum of MPTP-monkeys and an important loss of DAT mRNA(-86% vs. Control) was observed in substantia nigra. Treatments for 1 month with either the D1 agonist SKF-82958 (3 mg/kg/day) or the D2 agonist cabergoline (0.25 mg/kg/day) had no effect on the lesion-induced decrease in NT and DAT binding sites or DAT mRNA levels. The decrease of striatal NT binding sites was less than expected from the decrease of DA content in this nucleus, suggesting only partial localization of NT receptors on nigrostriatal DAergic projections. These data also suggest that under severe DA denervation, treatment with D1 or D2 DA agonists does not modulate NT receptors and DAT density.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1999

Differential ontogenetic patterns of levocabastine-sensitive neurotensin NT2 receptors and of NT1 receptors in the rat brain revealed by in situ hybridization.

The postnatal ontogeny of the levocabastine-sensitive neurotensin receptor (NT2) mRNA was studied by in situ hybridization in the rat brain and compared with the distribution of the levocabastine-insensitive NT1 receptor. NT2 receptor mRNA was absent at birth from all brain structures except the ependymal cell layer lining the ventricles. The development of NT2 receptor mRNA followed three ontogenetic patterns. The first pattern, involving the majority of the cerebral gray matter, was characterized by a continuous increase from postnatal day 5 (P5) to P30. The second one, involving regions rich in myelinated fibers such as the corpus callosum and lacunosum moleculare layer of the hippocampus, exhibited a pronounced increase between P5 and P10, peaked at P15 and was followed by a plateau or a slight decrease. The third pattern was observed in the ependymal cell layer lining the olfactory and lateral ventricles, where the high labeling already present at birth continued to increase during development. These different developmental patterns could reflect the variety of cells expressing NT2 receptor mRNA, including neurons, protoplasmic astrocytes in gray matter, fibrous astrocytes present in myelinated fibers tracts, and ependymal cells. In contrast, NT1 receptor mRNA, which seems to be associated only with neurons, was highly and transiently expressed during the perinatal period in the cerebral cortex, hippocampus and striatal neuroepithelium. Other regions, notably the ventral tegmental area and substantia nigra compacta, exhibited a gradual increase in NT1 receptor signal, reaching adult levels by P21. Both the differential localization and ontogenetic profiles of NT1 and NT2 receptor mRNAs suggest different involvement of these two receptors in brain functions and development.

Amygdala↗
PubMed1999

In vitro effects of dexamethasone on human corneal keratocytes.

PURPOSE: To investigate whether cultured human keratocytes express the glucocorticoid receptor (GR) and to assess the influence of dexamethasone (DEX) on these cells. METHODS: Human keratocytes were cultured in medium supplemented with various concentrations of DEX (ranging from 10(-10) to 10(-4) M). Cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-s ulfophenyl)-2H-tetrazolium inner salt (MTS) assay at 2, 4, and 6 days of culture. Some experiments were performed in the presence of mifepristone (RU38486), an antiglucocorticoid molecule. The early phase of apoptosis was studied by means of keratocyte staining with a fluorescein conjugate of annexin V and propidium iodide, and cells were analyzed by flow cytometry. Glucocorticoid receptor mRNA was detected in keratocytes by means of reverse transcription-polymerase chain reaction (RT-PCR). Immunocytochemical staining of the cells was performed with a monoclonal anti-human GR. RESULTS: RT-PCR and immunocytochemistry showed the expression of GR (mRNA and protein) in cultured keratocytes. Dexamethasone significantly increased keratocyte proliferation with concentrations ranging from 10(-9) to 10(-5) M, with a maximum effect at 10(-7) M (P < 0.005). Dexamethasone's proproliferative effect was inhibited by RU38486. However, DEX also induced apoptosis of cultured keratocytes at any concentration used. CONCLUSIONS: These results indicate that cultured human keratocytes express the GR and proliferate in response to DEX stimulation (10(-9)-10(-5) M), which also induces keratocyte apoptosis.

Apoptosis↗