The present study revealed that the human EOMs have a very complex fiber type and MyHC composition and differ significantly from the EOMs of other species. The features of the LP were distinct from those of the four recti, the obliquus superior, and the limb muscles.
The extraocular muscles (EOMs) are a unique group of specialized muscles that are anatomically and physiologically distinct from other skeletal muscles. Perhaps the most striking characteristic of the EOMs is their differential sensitivity to disease. EOMs are spared in Duchenne's muscular dystrophy (DMD) despite widespread involvement of other skeletal muscles. Conversely, they are early and prominent targets in myasthenia gravis and mitochondrial myopathies. It is unclear how EOMs achieve such specialization or a differential response to diseases; however, this has been attributed to a unique, group-specific pattern of gene expression or "allotype." To begin to address these issues as well as define the human EOM allotype, we analyzed the human EOM transcriptome using oligonucleotide-based expression profiling. Three hundred thirty-eight genes were found to be differentially expressed in EOM compared with quadriceps femoris limb muscle, using a twofold cutoff. Functional characterization revealed expression patterns corresponding to known metabolic and structural properties of EOMs such as expression of EOM-specific myosin heavy chain (MYH13) and high neural, vascular, and mitochondrial content, suggesting that the profiling was sensitive and specific. Genes related to myogenesis, stem cells, and apoptosis were detected at high levels in normal human EOMs, suggesting that efficient and continuous regeneration and/or myogenesis may be a mechanism by which the EOMs remain clinically and pathologically spared in diseases such as DMD. Taken together, this study provides insight into how human EOMs achieve their unique structural, metabolic, and pathophysiological properties.
The long term effects of two dose regimens of latanoprost (PhXA41) administered to eyes concomitantly treated with timolol which had not adequately been controlied by timolol alone were compared. A total of 50 patients, 17 with primary open angle glaucoma and 33 with capsular glaucoma, were recruited from five clinics. All had glaucomatous visual field defects and an intraocular pressure (IOP) of at least 22 mm Hg despite treatment with 0*5% timolol twice daily. Patients were randomised to two treatment groups. In one group 0.006% latanoprost was given twice daily, in the other group placebo was given at 8 am and latanoprost at 8 pm for 3 months, with concomitant timolol treatment in both groups. Average daytime IOP (mean (SD)) at baseline (on timolol alone) and after 4 and 12 weeks' treatment was 24*8 (3.6), 16-8 (4.3), and 15*7 (2.4) mm Hg respectively with once daily application of latanoprost and 24-9 (2.9), 18*1 (3.0), and 18-0 (3.6) mm Hg respectively with latanoprost twice daily. No clinically significant side effects were observed during treatment. Latanoprost causes a marked and sustained IOP reduction in eyes which are also being treated with timolol. Latanoprost given once daily is at least as effective and probably superior to a twice daily dose regimen (BrJ Ophthalmol 1995; 79: 12-16) Several previous studies have demonstrated that the phenyl substituted prostaglandin F2a analogue, 13,14-dihydro-17-phenyl-18, 19, 20-trinor-prostaglandin F2a-isopropylester (latanoprost, PhXA41) and its epimeric mixture PhXA34 reduce significantly the intraocular pressure (IOP) in normal, ocular hypertensive, or glaucomatous eyes."18 The present study was undertaken to obtain more information on dose regimen, long term effect, and additivity to a 13 adrenergic antagonist, timolol.Latanoprost has a long duration of effect on IOP, but whether it should be administered once of twice daily is unclear. In two dose finding studies with the epimeric mixture PhXA34 a duration ofat least 24 hours was observed but the effect 24 hours after the dose was less pronounced than that seen at 12 hours after the dose.' 2 Such an attenuation of the effect was not observed in a study on hospitalised patients treated with latanoprost,7 and in one dose regimen study administration of 0-006% latanoprost once daily was at least as effective as twice daily.4In a first dose finding study with twice daily administrations of latanoprost, ocular hypertensive eyes were treated for 4 weeks.5 There was no significant difference between the three concentrations of latanoprost eye drops used; 0 0035%, 0 006%, and 0-0115%, and all were significantly better than placebo. The initial response, on the second day of treatment, was good with a 31-38% reduction of the IOP, but after 1 week of treatment there was some diminution of effect and after 4 weeks the IOP reduction was between 19 and 22% for the three concentrations of latanoprost used. A partial diminution in the IOP effect was also observed by Camras et al after 5 days of treatment t...
. Purpose: To evaluate postoperative ocular involvement in Swedish liver transplant (LT) recipients with familial amyloid polyneuropathy (FAP). Methods: Routine ophthalmological examinations were performed in 48 LT recipients, with particular attention given to amyloid deposition in the anterior segment and the vitreous body. Medical records were scrutinized for information regarding neurological impairment at the time of the LT. The diagnosis was secured in all cases by examining for amyloid deposits in biopsy specimens and positive genetic testing for amyloidogenic transthyretin (ATTR) Val30Met mutation. Results: Six patients (12.5%) developed vitreous opacities within the post‐LT observation period. The first opacities were seen 40 months after transplantation, 8 years after the onset of systemic disease. Four patients (8%) developed secondary glaucoma, the first of which was observed 18 months after the procedure and 6.5 years after the onset of disease. Sixteen patients (33%) developed deposits on the anterior surface of the lens. Scalloped pupillary margins were noted in 10 patients (21%). Conclusion: The prevalence of eye complications increases with time after LT and regular follow‐up is necessary, especially to disclose the development of glaucoma – a complication with insidious symptoms of which patients are normally unaware.
The human EOMs showed important differences in laminin isoform composition and capillary density when compared with human limb muscle and muscles of other species. The presence of additional laminin isoforms other than laminin-2 in the BM of the extrasynaptic sarcolemma could partly explain the sparing of the EOMs in Lnalpha2-deficient congenital muscular dystrophy.
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