Purpose. BRAF T1796A activating mutations have been found in a high proportion of cutaneous melanomas, cutaneous nevi, and papillary thyroid carcinoma and in a small fraction of other cancers. This study was designed to investigate the incidence of BRAF T1796A mutation in uveal melanoma. methods. Twenty-nine formalin-fixed, paraffin-embedded posterior uveal melanomas were included in the study. DNA was extracted from the paraffin sections followed by PCR amplification of exon 15 and detection of the common BRAF missense mutation (T→A transversion at nucleotide 1796) using restriction enzyme analysis. results. Although positive cutaneous melanoma control cell lines harbored the T1796A BRAF mutation, none of the 29 uveal melanomas harbored the mutation. conclusions. These data suggest that BRAF T1796A activating mutation is not common in primary uveal melanoma. These findings are in accord with known differences in tumorigenesis between uveal and cutaneous melanomas.
1 August 2005 in Investigative Ophthalmology & Visual Science
Purpose. The early response and survival of oligodendrocytes after axonal stroke and their potential contribution to neuronal survival in vivo have not been adequately addressed. The purpose of this study was to investigate the changes occurring in the retina and optic nerve (ON) in anterior ischemic optic neuropathy (AION), using a c-fos transgenic mouse model. methods. A new mouse model of AION (rodent AION) was developed to evaluate the in vivo stress response of oligodendrocytes and retinal ganglion cells (RGCs) in a transgenic mouse strain, using the immediate early stress-response gene c-fos, RT-QPCR technology, immunohistochemistry, and electron microscopy. Confocal microscopy was used with cell-specific antibodies to characterize the timing of cells responding to rAION. The TUNEL assay detected cells undergoing apoptosis. Ultrastructural changes were analyzed by electron microscopy. results. In rAION, oligodendrocytes rapidly respond in vivo to ischemic ON damage, with c-fos activation as an early detectable event. Early evidence of progressive oligodendrocyte stress, is followed by demyelination, wallerian degeneration of the ON, and oligodendrocyte and RGC death far from the primary lesion. conclusions. After rAION induction oligodendrocytes, as well as RGCs, undergo progressive stress, with dysfunction and apoptosis. The findings lead to a proposal that progressive retrograde oligodendrocyte stress, away from the primary lesion, is an important factor after ischemic optic neuropathy. Postinduction demyelination must be addressed for effective neuroprotection of ischemic and hypoxic white matter.
1 September 2005 in Investigative Ophthalmology & Visual Science
Purpose. To gain a better understanding of the molecular events leading to the development of conjunctival melanocytic lesions and conjunctival melanoma, this study was conducted to investigate the presence of T1799A BRAF oncogenic mutation in these lesions. methods. Forty-eight surgically excised conjunctival melanocytic lesions from 48 patients were examined for the presence of the BRAF T1799A mutation. Twenty-eight lesions were conjunctival nevi, of which 20 were excised from children younger than 18 years. Fifteen lesions were conjunctival primary acquired melanosis (PAM; 11 without atypia and 4 with atypia) and five were conjunctival melanomas. To detect the BRAF T1799A mutation, both a newly developed kit (Mutector; TrimGen, Sparks, MD) and direct DNA sequence analysis of exon 15 after PCR amplification were used. results. The T1799A BRAF mutation was identified in 14 of 28 (50%) conjunctival nevi analyzed, but in none of the 15 conjunctival PAMs, with and without atypia. The T1799A BRAF mutation was identified in two of the five (40%) conjunctival melanomas. There was no difference in the BRAF mutation detected in conjunctival nevi in children or adults, as the BRAF mutation was detected in 50%. conclusions. The results showed that conjunctival nevi, similar to skin nevi, have a high frequency of oncogenic BRAF mutations. Furthermore, the results suggest that the oncogenic event leading to BRAF mutations affect only conjunctival nevi and not conjunctival PAM. The clinical significance of these observations remains to be determined.
1 August 2006 in American Journal of Ophthalmology
To evaluate by ultrasound biomicroscopy (UBM) the exact position of a posterior chamber intraocular lens (PC IOL) implanted above a posterior capsule tear and to correlate the findings with the outcomes and complication rate. Department of Ophthalmology, Rabin Medical Center, Petah Tiqva, Israel. In a retrospective noncomparative case series, 36 patients (36 eyes) who had extracapsular cataract extraction (ECCE) complicated by capsular tear were evaluated. In all cases, a PC IOL was implanted above the remnant of the capsule without suturing. Ultrasound biomicroscopy was performed to study the exact position of the optic and haptic. The outcomes and complication rate were determined from patient examinations performed during a follow-up of 1 to 6 years. Optic tilt was found in 20 of 36 patients (56%). In 17 patients (47%), both haptics were located in the sulcus. In 15 patients (42%), 1 haptic was observed in the sulcus and 1 in the bag or elsewhere. No correlation was found between the position of the optic and the location of the haptics. Minimal postoperative complications were observed, and only 1 patient required another surgery for a dislocated IOL. By UBM, half the patients had optic tilt and more than half the IOLs were not implanted in the sulcus, the intended location.