Publications by authors named "Selcen Celik"

17 Publications

  • Page 1 of 1

Effect of lateral rectus muscle resection on abduction in Duane retraction syndrome type 1.

Int Ophthalmol 2021 Mar 13;41(3):797-803. Epub 2020 Nov 13.

University of Health Sciences Beyoğlu Eye Research and Training Hospital, Istanbul, Turkey.

Purpose: To assess the effect of lateral rectus muscle resection on abduction in Duane retraction syndrome (DRS) type 1.

Methods: The medical records of patients with DRS type 1 were reviewed retrospectively. Fifteen patients who underwent lateral rectus resection were included. Prism and cover test and the Krimsky test were used to detect deviations. Ocular ductions, abnormal head position (AHP), and globe retraction were recorded.

Results: Nine (60.0%) patients were female. The mean age was 13.1 ± 2.3 (range, 2-34) years. Left eyes were included in ten (66.7%) patients. Mean follow-up time was 37.6 ± 16.6 (range, 6-70) months. All patients had AHP, 13 patients had mild globe retraction, and 2 patients had no globe retraction preoperatively. Mean lateral rectus resection was 3.1 ± 0.7 (range, 2.0-4.5) mm, and the mean medial rectus recession was 4.4 ± 0.6 (range, 3.0-5.0) mm. The mean preoperative deviation decreased from 23.3 ± 6.9 (range, 14-35) prism diopters (pd) to 2.2 ± 4.1 (range, 0-10) pd at near, and from 23.6 ± 7.1 (range, 14-35) pd to 1.8 ± 3.5 (range, 0-10) pd at distance, at 6 months postoperatively (p = 0.01). The mean limitation in abduction decreased from - 3.2 ± 0.9 to - 1.3 ± 1.1 postoperatively (p < 0.001). AHP resolved in all patients. There was not a limitation in adduction or a worsening of globe retraction in any patient.

Conclusion: Lateral rectus resection can be used to improve abduction in patients with DRS type 1 who have mild globe retraction. We assume that this procedure has no worsening effect on globe retraction in appropriate cases.
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http://dx.doi.org/10.1007/s10792-020-01632-wDOI Listing
March 2021

Muscle belly union surgery with or without medial rectus recession for the treatment of high myopic strabismus fixus.

J AAPOS 2020 10 9;24(5):278.e1-278.e5. Epub 2020 Oct 9.

University of Health Sciences Beyoğlu Eye Research and Training Hospital, İstanbul, Turkey.

Purpose: To evaluate the results of surgery involving the union of the superior rectus muscle and the lateral rectus muscle with or without medial rectus recession (MRc) for the treatment of high myopic strabismus fixus over a 20-year period.

Methods: The medical records of patients who underwent muscle belly union for the treatment of high myopic strabismus fixus were reviewed retrospectively. Patients were classified according to the timing of MRc. In group 1, MRc was performed before muscle union surgery; in group 2, MRc was performed concurrent with muscle union surgery; in group 3, MRc was not performed; in group 4, MRc was performed after muscle union surgery.

Results: A total of 50 eyes of 40 patients were included. Mean esotropia decreased from 57.27 ± 25.45 (range, 8-100) before surgery to 11.67 ± 13.85 (range, -18 to 45) after (P < 0.001); mean hypotropia, from 6.05 ± 9.13 (range, 0-13) before to 1.20 ± 3.03 (range, 0-10) after (P < 0.001). Mean abduction improved from -2.82 ± 1.17 (range, -4 to 0) before to -0.75 ± 0.92 (range, -3 to 0) after (P < 0.001); mean elevation, from -1.62 ± 1.62 (range, -4 to 0) before to -0.57 ± 0.90 (range, -3 to 0) after (P < 0.001). Preoperative esotropia and postoperative limitation in abduction were significantly lower in group 3 (P = 0.03; P = 0.01).

Conclusions: Muscle union surgery successfully corrected the restrictive esotropia and hypotropia. MRc in addition to muscle union surgery was not necessary for some patients, for whom preoperative esotropia was lower.
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http://dx.doi.org/10.1016/j.jaapos.2020.06.012DOI Listing
October 2020

Assessment of Refractive Error Changes and Factors for Decompensation in Patients With Fully Accommodative Esotropia.

J Pediatr Ophthalmol Strabismus 2020 07;57(4):217-223

Purpose: To determine the factors affecting the risk of deterioration and evaluate the refractive error change in patients with fully accommodative esotropia.

Methods: Patients diagnosed as having fully accommodative esotropia (esotropic deviation that started before 7 years of age and less than 8 to 10 prism diopters [PD] of esotropia with full hyperopic correction and/or bifocals) were included in this retrospective population-based cohort study. Refractive error changes were recorded. For comparisons, patients were divided into two groups: nondecompensated fully accommodative esotropia group and decompen-sated fully accommodative esotropia group.

Results: Two hundred and twenty-three patients met the inclusion criteria. The mean follow-up time was 5.94 ± 0.31 years (range: 5 to 8 years). The changes in spherical equivalent in the younger than 7 years, 7 to 12 years, and 12 to 17 years groups were statistically significant (P < .001). The decrease of hypermetropia was 0.13 diopters/year between 7 and 12 years and 0.06 diopters/year between 12 and 17 years. Forty-one of 223 patients (18.4%) discontinued spectacle therapy during the follow-up period. Hyperopic error and presence of amblyopia were lower, whereas visual acuity level and presence of near-distance disparity were higher in the spectacle discontinuation group (P < .001, .007, .01, and 0.01, respectively). Deterioration of fully accommodative esotropia occurred in 30 of 223 patients (13.5%). Boys were more likely to require strabismus surgery (P = .32). The mean age at presentation, esotropia angle with and without refractive correction at both near and distance fixation, near distance disparity, and inferior oblique overaction were significantly higher in patients with decompensated fully accommodative esotropia.

Conclusions: Hyperopic error increased from the initial level until 7 years of age, followed by a myopic shift thereafter. Few children had resolution of fully accommodative esotropia and could discontinue spectacle therapy. Children with male gender, higher esotropia angle, older age at presentation, near-distance disparity, and inferior oblique overaction experienced a greater deterioration of the fully accommodative esotropia. [J Pediatr Ophthalmol Strabismus. 2020;57(4):217-223.].
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http://dx.doi.org/10.3928/01913913-20200504-02DOI Listing
July 2020

Comparison of different tendon transposition techniques for the treatment of monocular elevation deficiency type 2.

J AAPOS 2020 02 31;24(1):8.e1-8.e4. Epub 2019 Dec 31.

University of Health Sciences, Beyoğlu Eye Research and Training Hospital, İstanbul, Turkey.

Purpose: To compare results of three different tendon transposition techniques (Knapp procedure and two modified techniques) for the treatment of type 2 monocular elevation deficiency (MED) patients.

Methods: The medical records of patients with MED type 2 operated on at a single institution from 2000 to 2016 were reviewed retrospectively. Patients were divided into three vertical transposition groups: (1) full tendon width, (2) augmented surgery; and (3) partial tendon width. Surgical success was defined as no severe limitation of upgaze, hypotropia of <6, and no hypertropia in primary position. Pre- and postoperative vertical deviations in the primary position and limitations in elevation levels were compared.

Results: A total of 39 patients were included. The pre- and postoperative deviations in the full-tendon group were 22.50 ± 4.17 and 3.50 ± 1.27, respectively; in the augmented surgery group, 23.75 ± 4.78 and 1.75 ± 1.14; and in the partial-tendon group, 20.50 ± 3.98 and 4.12 ± 2.78. Corrected vertical deviations were 19, 23, and 16, respectively. The pre- and postoperative limitation of elevations were -2.80 and -0.80 in the full-tendon group, -3.20 and -0.90 in the augmented surgery group, and -2.37 and -1.12 in the partial-tendon group. The pre- and postoperative vertical deviation improvements and limitations of elevation were statistically significant (P < 0.05) in all groups. Success was achieved in 29 patients (74%).

Conclusions: In this study cohort, all three procedures were reasonably effective in improving vertical deviations and limitation of elevation.
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http://dx.doi.org/10.1016/j.jaapos.2019.09.015DOI Listing
February 2020

Cyclic strabismus: what measured angle of strabismus should guide surgery?

Strabismus 2019 12 20;27(4):205-210. Epub 2019 Nov 20.

Strabismus Department, University of Health Sciences Beyoğlu Eye Research and Training Hospital, Istanbul.

: Here we aimed to describe seven pediatric patients with cyclic strabismus and report the outcome of their surgical treatment.: Seven children with acquired esotropia manifesting in a 48-h cycle were included in the study. Four of them were boys, and three of them were girls. All cases had a large angle of deviation and associated suppression on the esotropic day and small angle of deviation with fusion on the other day. A complete ocular motility examination was performed for seven consecutive days. For all cases, we planned strabismus surgery according to the amount of deviation on the strabismic day. Postoperatively, the deviation angles were recorded at the first week, first month, and third month. Later, the patients were examined at 3-month intervals.: The mean age at presentation was 4.42 ± 3.69 years (1-12 years). The mean angle of esotropia at near fixation preoperatively was 36.4 ± 14.9 pd (prism dioptre) (20-60 pd) on the esotropic day. The mean angle of esotropia on the esotropic day at distance fixation was 32.1 ± 6.9 pd (20-40 pd). The mean follow-up period was 18.4 ± 5.5 months (12-25 months). The mean duration of esotropia before surgery was 11.1 ± 9.4 months (3-29 months). Following surgery, orthophoria within 10 pd was achieved and maintained in all cases.: When treating children with cyclic strabismus, the best surgical results can be achieved when surgery is planned according to the amount of deviation on the strabismic day.
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http://dx.doi.org/10.1080/09273972.2019.1692041DOI Listing
December 2019

Vertical rectus muscle union combined with lateral rectus plication for complete abducens nerve palsy.

Int Ophthalmol 2020 Feb 23;40(2):423-429. Epub 2019 Oct 23.

Strabismus Department, Beyoglu Eye Research and Training Hospital, University of Health Sciences, Bereketzade Mahallesi, Bereketzade Cami Sk. 2/4, 34437, Beyoğlu, İstanbul, Turkey.

Purpose: The aim of this study was to report our postoperative results concerning the vertical rectus (VR) muscle union combined with lateral rectus (LR) plication for the treatment of large-angle esotropia (ET) in complete abducens nerve palsy.

Methods: Medical records from 36 patients who had undergone the VR union procedure for ET treatment due to sixth-nerve palsy between July 2014 and July 2018 at Beyoglu Eye Research and Training Hospital were reviewed. One week before surgery, all patients underwent a 4-IU botulinum toxin A (btx) injection into the ipsilateral medial rectus (MR). All patients then underwent a VR muscle union procedure. A non-absorbable suture was inserted through the lateral muscular margin of each VR muscle at approximately 1/5 the width from the edge at 10 mm distance from the VR insertion. Both sutures were then tied to each other above the LR. Plication of the LR muscle using a non-absorbable suture was performed in all cases.

Results: The study population consisted of 14 (38.9%) females and 22 (61.1%) males. The mean age was 36.31 ± 19.16 years. The mean preoperative deviation angle in primary gaze into distance was 47.77 ± 18.48 prism diopter (PD). The mean deviation angle 1 year after surgery was - 1.0 ± 6.62 PD. Abduction improved from - 4.27 ± 0.46 to - 1.88 ± 0.96.

Conclusion: The VR muscle union in combination with LR plication appears to be an effective treatment procedure for complete abducens nerve palsy patients.
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http://dx.doi.org/10.1007/s10792-019-01200-xDOI Listing
February 2020

Optical Coherence Tomography Angiography: Are There Any Changes in Measurements After Strabismus Surgery?

J Pediatr Ophthalmol Strabismus 2019 Mar;56(2):95-100

Purpose: To evaluate the possible hemodynamic changes following strabismus surgery via optical coherence tomography angiography.

Methods: Thirty-two eyes of 16 patients who underwent strabismus surgery in one eye were included in the study. Fellow eyes were used as a control group. The vessel densities of the superficial and deep capillary plexus and superficial and deep foveal avascular zones were measured preoperatively and 3 months postoperatively.

Results: The mean superficial and deep foveal avascular zones measurements were 0.84 ± 0.09 and 0.76 ± 1.13 mm, respectively. The mean vessel density of the superficial capillary plexus was 1.23 ± 0.12 and 11.13 ± 1.04 mm preoperatively in the 1- and 3-mm zones, respectively, whereas the mean vessel density of the deep capillary plexus was 1.13 ± 0.16 and 10.11 ± 1.28 mm preoperatively. Postoperatively, the mean superficial and deep foveal avascular zones changed to 0.20 ± 0.13 and 0.23 ± 0.12 mm, respectively. Postoperatively, the mean vessel density of the superficial capillary plexus changed to 1.47 ± 0.11 and 12.75 ± 1.10 mm, and the mean vessel density of the deep capillary plexus changed to 1.56 ± 0.12 and 13.91 ± 1.35 mm in 1- and 3-mm zones, respectively. There was a statistically significant increase in vessel density measurements of the superficial and deep capillary plexus, and a statistically significant decrease in measurements of the superficial and deep foveal avascular zone postoperatively (P < .05). In the fellow eyes, there was no statistically significant change in any of the measurements (P > .05).

Conclusions: Following strabismus surgery, vessel density of the fovea may increase and the foveal avascular zone may decrease according to optical coherence tomography angiography measurements. [J Pediatr Ophthalmol Strabismus. 2019;56(2):95-100.].
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http://dx.doi.org/10.3928/01913913-20190128-01DOI Listing
March 2019

Surgical Management in Type 1 Monocular Elevation Deficiency.

J Pediatr Ophthalmol Strabismus 2018 Nov 27;55(6):369-374. Epub 2018 Jul 27.

Purpose: To evaluate the outcome of surgical treatment in patients with type 1 monocular elevation deficiency.

Methods: Patients who were diagnosed as having type 1 monocular elevation deficiency by forced duction test and exaggerated traction test between 2000 and 2016 were retrospectively reviewed. Epidemiologic and clinical features of the patients were noted. The efficacy of ipsilateral inferior rectus recession to vertical misalignments and limitation of elevation were evaluated. The clinical features of the patients who did not achieve surgical success after inferior rectus recession were determined. The surgical and functional results of contralateral superior rectus recession were evaluated for patients who had residual hypotropia under inferior rectus recession.

Results: Thirty-nine patients were included in the study. Preoperatively, vertical deviations were 20.53 ± 4.50 prism diopters (PD) for near and 22.21 ± 5.12 PD for distance. After inferior rectus recession, the amount of vertical deviation corrected was 15 ± 1.14 PD for near and 17.01 ± 2.00 PD for distance. Ten (25.64%) patients did not achieve surgical success (> 6 PD residual hypotropia). Nine patients (preoperative inferior rectus recession measurements = 28.77 ± 7.25 PD for near and 27 ± 7.44 PD for distance) underwent contralateral superior rectus recession as a second surgery. After contralateral superior rectus recession, 7 of 9 (77.78%) patients achieved surgical success. The limitation of elevation significantly improved after both surgeries (Wilcoxon test, P < .05). No diplopia or other complications after surgeries were reported.

Conclusions: Inferior rectus recession is the first surgical option for patients with type 1 monocular elevation deficiency. Contralateral superior rectus recession is an effective alternative surgical treatment for residual hypotropia after ipsilateral inferior rectus recession. [J Pediatr Ophthalmol Strabismus. 2018;55(6):369-374.].
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http://dx.doi.org/10.3928/01913913-20180620-04DOI Listing
November 2018

Measurement of extraocular horizontal muscle insertion distance via anterior segment optical coherence tomography of healthy children and comparison with healthy adults.

Int Ophthalmol 2019 May 26;39(5):1037-1042. Epub 2018 Mar 26.

Beyoglu Eye Education and Research Hospital, University of Health Sciences, Bereketzade Mah, Meşrutiyet Cad No:73, 34421, Istanbul, Turkey.

Purpose: The aim of the study was to determine the corneal limbus-extraocular muscle insertion distance (LID), via anterior segment optical coherence tomography, in healthy children and healthy adults and to compare the results of the measurements of the two groups.

Methods: Muscle limbus distances were measured using AS-OCT in 60 healthy cases in two groups. Children aged 8-13 years were evaluated as group 1, and healthy adults aged 25-30 years were evaluated as group 2. Measurements of 120 horizontal muscles were taken by one doctor (OBO). The values were compared according to age and gender groups, and correlation between LID measurements and spherical equivalent. Statistical evaluation was performed using SPSS 16 for Windows with the Student's t test and Pearson correlation coefficient test.

Results: LID measurements for MR and for lateral rectus (LR) were 5.74 ± 0.75 and 6.74 ± 1.11 mm, in the pediatric age-group, and 5.73 ± 0.75 and 6.84 ± 1.15 mm, in the adult age-group, respectively. There was no statistically significant difference between the two groups in terms of MR distances. There was a slight increase in the adult values, for the LR distance. There was no significant difference in terms of gender. Correlation was found 0.62 for MR and 0.46 for LR between LID measurements and spherical equivalent in the pediatric age-group.

Conclusions: In healthy individuals, different imaging modalities can be used to measure LID, but AS-OCT can be used in pediatric age-groups as a preferred imaging method because it is easy and noninvasive.
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http://dx.doi.org/10.1007/s10792-018-0903-5DOI Listing
May 2019

Simplified approach of Gokyigit's technique for complete cranial nerve third palsy.

Int Ophthalmol 2019 Jan 23;39(1):111-116. Epub 2017 Dec 23.

Beyoglu Eye Training and Research Hospital, University of Health Sciences, Bereketzade Cami Sokak No: 2 Beyoglu, Istanbul, Turkey.

Purpose: To evaluate a simpler approach of the medial transposition of split lateral rectus technique in patients with complete third nerve palsy.

Methods: All eyes with complet third nerve palsy were followed in our Strabismus Department between 2014 and 2016. All patients had complete oculamotor nerve palsy. All patients assed routine ophthalmologic examination. Also the ocular deviation, horizontal and vertical ocular alignments were measured at 6 m and at 1/3 m using the Krimsky corneal reflection test and alternate prism cover test with best optical correction. Same surgeon (BG) performed all procedures in general anesthesia. In this procedure, same Gokyigit's technique except upper and lower part of lateral rectus muscle was passed under the superior oblique tendon and inferior oblique tendon. Final deviation from 0 to 14 PD was considered a successful result.

Results: Eight patients were included in the study. The average ages were 39.4 years and male to female ratio 5:3. Patients had a preoperative horizontal deviation - 42.5 ± 2.7 PD and postoperative horizontal deviation - 1.7 ± 2.6 PD. All patients follow-up time were at least 6 months.

Conclusions: Achieved to acceptable alignment in primary position, manage to diplopia and cosmetical appearance are the main aims of patients with third nerve palsy.
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http://dx.doi.org/10.1007/s10792-017-0794-xDOI Listing
January 2019

Medial Rectus Bridge Faden Operations in Accommodative and Partially Accommodative Esotropia With Convergence Excess.

J Pediatr Ophthalmol Strabismus 2017 Nov 9;54(6):369-374. Epub 2017 Oct 9.

Purpose: To evaluate the results of the bilateral bridge Faden operation on the medial rectus muscles with and without recession in the treatment of accommodative and partially accommodative esotropia with convergence excess.

Methods: A retrospective analysis was performed on the medical records of 103 patients who underwent the bridge Faden operation on both medial rectus muscles, with or without recession, for the treatment of accommodative and partially accommodative esotropia with convergence excess. Preoperative and postoperative near and distance deviations and near-distance disparities were evaluated.

Results: The study population consisted of 38 (37%) girls and 65 (63%) boys. The mean age was 9.32 ± 5.83 years (range: 1 to 18 years) and the mean follow-up period was 14.49 ± 2.78 months. Fifty-one patients underwent the bridge Faden operation on both medial rectus muscles with recession (recession group) and 52 patients underwent the bridge Faden operation on both medial rectus muscles without recession (no recession group). The mean preoperative amount of esotropia at near was 43.51 ± 7.00 and 24.24 ± 3.56 prism diopters (PD) for the recession and no recession groups, respectively. The mean preoperative amount of esotropia at distance was 26.63 ± 6.86 and 9.22 ± 2.09 PD for both groups, respectively. The mean preoperative near-distance disparity was 17.14 ± 3.00 and 14.05 ± 4.14 PD for both groups, respectively. In both groups, there was a statistically significant difference in the near and distance deviations and the near-distance disparity between preoperative and postoperative values (P < .05). Postoperatively, there was no significant difference between 1 month, 6 months, and 1 year and between 6 months and 1 year (P > .05).

Conclusions: The bridge Faden operation on both medial rectus muscles either with or without recession was a successful surgical procedure in patients with accommodative and partially accommodative esotropia. During the follow-up period, the success rates did not decrease. [J Pediatr Ophthalmol Strabismus. 2017;54(6):369-374.].
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http://dx.doi.org/10.3928/01913913-20170801-03DOI Listing
November 2017

The effect of DNA damage on the pattern of immune-detectable DNA methylation in mouse embryonic fibroblasts.

Exp Cell Res 2015 Nov 26;339(1):20-34. Epub 2015 Sep 26.

Human Reproduction Unit, Kolling Institute for Medical Research, Sydney Medical School, University of Sydney, Sydney 2065, Australia.

The methylation of cytosine at CpG dinucleotides (5 meC) is an important epigenetic mechanism that governs genome stability and gene expression. Important ontological and pathological transitions are associated with marked global changes in detectable levels of methylation. We have previously found two pools of immune-detectable 5 meC exist within cells, a pool that can be detected after acid treatment of fixed cells to denature chromatin and another large but variable pool that requires a further tryptic digestion step for complete epitope retrieval. The trypsin-sensitive pool has been shown to be largely associated with the heterochromatic fraction (by a heterochromatin marker, HP1-β) of the genome, and the size of this pool varies with the growth disposition of cells. Since DNA damage imposes large changes on chromatin structure the present study analyzed how such changes influences the faithful immunological detection of 5 meC within mouse embryonic fibroblasts. DNA damage was induced by either UV-irradiation or doxorubicin treatment, each of which resulted in increased levels of immune-detectable 5 meC at 24-48 h after treatment. There was a marked trypsin-sensitive pool of 5 meC in these cells which was significantly increased after DNA damage. The increased levels of 5 meC staining predominantly co-located with heterochromatic foci within nuclei, as assessed by HP1-β staining. The relative amount of masked 5 meC after DNA damage was positively associated with increased levels of HP1-β. The methyl binding protein, MBD1, was a less reliable measure of changes in 5 meC, with a significant fraction of 5 meC not being marked by MBD1. The cyto-epigenetic approaches used here reveal dynamism in the levels and localization of immune-detectable 5 meC within the nuclei of fibroblasts in response to DNA damage.
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http://dx.doi.org/10.1016/j.yexcr.2015.08.017DOI Listing
November 2015

Methylation analysis of the DAPK1 gene in imatinib-resistant chronic myeloid leukemia patients.

Oncol Lett 2015 Jan 6;9(1):399-404. Epub 2014 Nov 6.

Department of Medical Biology, Faculty of Medicine, Ankara University, Sihhiye, Ankara 06100, Turkey.

Death-associated protein kinase-1 () is a pro-apoptotic gene that induces cellular apoptosis in response to internal and external apoptotic stimulants. The silencing of can result in uncontrolled cell proliferation, indicating that it may have a role in tumor suppression. activity can be inhibited by the cytosine methylation that occurs in its promoter region. These methylation changes in the promoter region of have been reported in a range of solid and hematological malignancies. In the present study, methylation was investigated in chronic myeloid leukemia patients (n=43) using bisulfite conversion followed by methylation-specific polymerase chain reaction. The present study included a number of patients who were identified to be resistant to the common chemotherapeutic agent imatinib (STI571, Gleevec, Glivec), exhibiting at least one mutation in the breakpoint cluster region-Abelson murine leukemia () gene. Thus, the patients in the present study were divided into two groups according to their response to imatinib therapy: Non-resistant (n=26) and resistant (n=17) to imatinib. Resistant patients were characterized by the presence of single or multiple mutations of the gene: i) T315I, ii) M351T, iii) E255K, iv) T315I and M351T or v) T315I, M351T and E255K. The present study identified that: i) The incidence of methylation was significantly higher in the resistant patients compared with the non-resistant patients; ii) the extent of resistance varied between mutation types; and iii) there was no methylation in any of the healthy controls. These findings indicate that methylation may be associated with a signaling pathway for imatinib resistance in chronic myeloid leukemia.
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http://dx.doi.org/10.3892/ol.2014.2677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246661PMC
January 2015

Understanding the complexity of antigen retrieval of DNA methylation for immunofluorescence-based measurement and an approach to challenge.

Authors:
Selcen Çelik

J Immunol Methods 2015 Jan 28;416:1-16. Epub 2014 Nov 28.

Human Reproduction and Development Unit, Kolling Institute for Medical Research, Sydney Medical School, University of Sydney, Sydney 2065, Australia. Electronic address:

Cytosine methylation (5-methylcytosine, 5meC) in the CpG-rich regions of the mammalian genome is an important epigenetic mechanism playing roles in transcription regulation and genomic stability. The abnormalities in DNA methylation can occur in various types of cancer and some genetic diseases. The measurement of DNA methylation is therefore important and there is a range of methodologies used to detect DNA methylation. Many methods based on bisulfite treatment appeared with a lack of specificity after recent discoveries of various modifications of methylated cytosine, however there are new treatments developed to overcome this limitation. Immunofluorescence is currently known to be able to specifically detect DNA methylation as it uses different antibodies against 5meC and its derivatives, but it is a semi-quantitative method. Immunofluorescence protocols commonly include fixation of cells followed by permeabilisation, antigen retrieval, and treatments with antibodies. Establishing the strategy for antigen retrieval of immunofluorescence is important to unmask epitopes (i.e. 5meC) from other proteins, and therefore to access the antigen of interest. There are many approaches used for antigen retrieval induced by acid, enzyme and/or heat. The selection of antigen retrieval method can depend on a variety of such antigen-based or cell-based conditions, since the dynamic structure of DNA and chromatin accounts for the complexity of involved proteins to mask the epitope. This review aims to specifically focus on the complexity of in situ detection of DNA methylation by immunofluorescence-based methods using antigen retrieval with the current understanding of DNA methylation mechanism, and suggests conditions for antigenic retrieval of 5meC epitope.
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http://dx.doi.org/10.1016/j.jim.2014.11.011DOI Listing
January 2015

The exit of mouse embryonic fibroblasts from the cell-cycle changes the nature of solvent exposure of the 5'-methylcytosine epitope within chromatin.

PLoS One 2014 4;9(4):e92523. Epub 2014 Apr 4.

Human Reproduction and Development Unit, Kolling Institute for Medical Research, Sydney Medical School, University of Sydney, Sydney, Australia.

The methylation of CpG dinucleotides is a pervasive epigenetic signature with critical roles governing genomic stability and lineage-specific patterns of gene expression. Reprogramming the patterns of CpG methylation accompanies key developmental transitions and the onset of some pathologies, such as cancer. In this study we show that levels of immuno-detectable 5meC decreased as mouse embryonic fibroblasts withdraw from the cell-cycle (became mitotically quiescent), but increased as they aged in culture. Two pools of 5meC epitope were found to exist, one solvent exposed after acid-induced denaturation of chromatin and another that required the additional step of tryptic digestion for detection. Proliferative cells displayed a relatively greater accumulation of detectable 5meC within the trypsin-sensitive pool than did quiescent cells. A substantial proportion of the 5meC was associated with a large number of heterochromatic foci scattered throughout nuclei, yet much of this was masked in a trypsin-sensitive manner, particularly in young proliferative cells. This study showed that the growth status of cells changed the level of solvent exposure of 5meC in fibroblasts and the long-accepted conventional methods of immunolocalization underestimate the level of 5meC in cells. This resulted in an artefactual assessment of the levels and patterns of nuclear localization of the antigen. The use of an additional tryptic digestion step improved antigen retrieval and revealed a more dynamic response of 5meC levels and distribution patterns to changes in the cell's growth state. This discovery will provide a basis for investigating the role of changes in chromatin structure that underlie this dynamism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092523PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976252PMC
June 2015

Repair of anterior staphyloma with dehydrated dura mater patch graft.

Ophthalmic Surg Lasers Imaging 2008 Jul-Aug;39(4):346-7

Department of Ophthalmology, Ankara University Faculty of Medicine, Ankara, Turkey.

A case of postoperative large anterior staphyloma of the sclera was treated with a dehydrated cadaveric dura mater patch graft. Structural integrity of the globe and a good cosmetic result were obtained after the surgery. During the follow-up of 2 years, no recurrence of staphyloma developed.
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http://dx.doi.org/10.3928/15428877-20080701-19DOI Listing
September 2008

Two-year results of intravitreal triamcinolone acetonide injection for the treatment of diabetic macular edema.

Int Ophthalmol 2007 Oct 24;27(5):299-306. Epub 2007 Apr 24.

Department of Ophthalmology, Faculty of Medicine, Ankara University, Mamak Street, Ankara 06100, Turkey.

Purpose: To investigate 2-year results of intravitreal triamcinolone acetonide injection for the treatment of diffuse diabetic macular edema unresponsive to previous laser photocoagulation.

Method: The study included 75 eyes of 75 diabetic patients with clinically significant diffuse macular edema that had failed to respond to previous laser photocoagulation. An intravitreal injection of triamcinolone acetonide at the dose of 4 mg/0.1 ml was administered. Best-corrected visual acuity was measured as the logarithm of the minimum angle of resolution (logMAR), and central macular thickness was obtained by optical coherence tomography at each visit. Intraocular pressure and lenticular status were also evaluated. Differences among measurements were evaluated by Friedman two-way analysis of variance by ranks. Mean follow-up period was 24.7 +/- 5.9 months.

Results: The mean central macular thickness, which was obtained 3 days, 1 month, 3 months, 6 months, 9 months, 12 months, 18 months and 24 months postoperatively, was significantly different from the baseline measurement (P < 0.001). Mean best-corrected logMAR visual acuity improved significantly from baseline at the 1- month and 3-month follow-up intervals (P < 0.05), but there was no significant change at the 6- month, 9-month, 12-month, 18-month or 24-month follow-up periods (P > 0.05). During the follow-up, 29 (38.7%) eyes received re-injection of intravitreal triamcinolone. Twenty-one (28%) eyes developed intraocular pressure values higher than 21 mmHg, and 18 (24%) eyes developed cataract. Thirteen (17.3%) eyes required cataract and/or glaucoma surgery.

Conclusions: In refractory diabetic macular edema, intravitreal triamcinolone effectively reduces foveal thickness and improves visual acuity in the short term, but with the extended follow-up, the number of recurrences and steroid-related complications were shown to increase. Nevertheless, it may be a therapeutic option in some patients that do not respond to previous laser photocoagulation.
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http://dx.doi.org/10.1007/s10792-007-9072-7DOI Listing
October 2007
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