Papers by Fatima Domellof
In muscular dystrophies, muscle fibers loose integrity and die, leading to significant suffering ... more In muscular dystrophies, muscle fibers loose integrity and die, leading to significant suffering and a shorter life. Strikingly, the extraocular muscles (EOMs), controlling eye movements, are spared and function well despite the disease progression. Although EOMs have been shown to have important differences compared to body musculature the mechanisms underlying this inherent resistance to muscle dystrophies remain largely unknown. Here, we demonstrate important differences in gene expression as a response to muscle dystrophies between the EOMs and trunk muscle in zebrafish via transcriptomic profiling. We show that the LIM-protein Fhl2 is upregulated in response to knockout ofdesmin,plectinandobscurin, intermediate filament proteins whose knockout causes different muscle dystrophies, and contributes to disease protection of the EOMs. Moreover, we show that ectopic expression offhl2bcan partially rescue the muscle phenotype in the zebrafish Duchenne muscular dystrophy modelsapje, si...
Investigative Ophthalmology & Visual Science, Jun 16, 2013
Investigative Ophthalmology & Visual Science, Jun 10, 2020
Investigative Ophthalmology & Visual Science, Jul 13, 2018
Purpose : Notch1 is suggested to play an important role during tissue development and in differen... more Purpose : Notch1 is suggested to play an important role during tissue development and in differentiation of the corneal epithelial cells whereas its inhibitors Dlk1 and Numb keep these cells in an ...
Investigative Ophthalmology & Visual Science, Jun 23, 2017
Investigative Ophthalmology & Visual Science, May 1, 2005
Frontiers in Neurology, Aug 17, 2018
Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As a... more Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary light reaction, this study aimed to evaluate the pupil responses to colored light stimuli in the pediatric population. Fifty-three children with normal vision and without any history of ocular disorders were tested with a portable pupillometer. Four test sequences were used: five dim blue (470 nm) stimuli presented in half log steps ranging from -3.15 to -1.15 log cd/m 2 after 3 min of dark adaptation, five red (622 nm) stimuli of -1.15, -0.7, -0.15, 0.3, and 0.85 log cd/m 2 after 1 min light adaptation, one bright blue stimulus of 2.2 log cd/m 2 and one bright red of 2 log cd/m 2 . The results were grouped by age: a younger group included 27 children aged from 3 to 10 years old and an older group included 26 from 10 and 1 month to 18 years old. The younger group had a smaller pupil diameter after dark adaptation compared with the older group. A linear regression defining the photopic threshold showed that younger subjects had a higher threshold, e.g., needed a brighter red stimulus to evoke a threshold pupil response comparable that of subjects. Age thus seems to influence outer retinal sensitivity at least as evaluated by the pupillary photopic threshold intensity. The post-illumination pupillary reaction was used as a marker of intrinsic melanopsin activity and did not show any difference between the two age groups.
Investigative Ophthalmology & Visual Science, May 1, 2003
Histochemistry and Cell Biology, May 12, 2022
We aimed to study aniridia-related keratopathy (ARK) relevant cell signaling pathways [Notch1, Wn... more We aimed to study aniridia-related keratopathy (ARK) relevant cell signaling pathways [Notch1, Wnt/β-catenin, Sonic hedgehog (SHH) and mTOR] in normal human fetal corneas compared with normal human adult corneas and ARK corneas. We found that fetal corneas at 20 weeks of gestation (wg) and normal adult corneas showed similar staining patterns for Notch1; however 10-11 wg fetal corneas showed increased presence of Notch1. Numb and Dlk1 had an enhanced presence in the fetal corneas compared with the adult corneas. Fetal corneas showed stronger immunolabeling with antibodies against β-catenin, Wnt5a, Wnt7a, Gli1, Hes1, p-rpS6, and mTOR when compared with the adult corneas. Gene expression of Notch1, Wnt5A, Wnt7A, β-catenin, Hes1, mTOR, and rps6 was higher in the 9-12 wg fetal corneas compared with adult corneas. The cell signaling pathway differences found between human fetal and adult corneas were similar to those previously found in ARK corneas with the exception of Notch1. Analogous profiles of cell signaling pathway activation between human fetal corneas and ARK corneas suggests that there is a less differentiated host milieu in ARK.
Investigative Ophthalmology & Visual Science, Apr 17, 2010
Investigative Ophthalmology & Visual Science, Jun 23, 2017
Nature communications, Mar 2, 2024
Investigative Ophthalmology & Visual Science, May 10, 2007
Investigative Ophthalmology & Visual Science, May 18, 2023
Investigative Ophthalmology & Visual Science, Jun 30, 2011
PURPOSE. To determine the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscle... more PURPOSE. To determine the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the laminin isoform composition of the basement membranes (BMs) in EOMs and limb muscles from donors with ALS. METHODS. Muscle samples collected at autopsy from ALS donors and from transgenic mice overexpressing human superoxide dismutase type I mutations (D90A or G93A), and agematched controls were analyzed with immunohistochemistry using antibodies against laminin chain (Ln)␣2, Ln␣4, Ln␣5, Ln1, Ln2, and Ln␥1. Neuromuscular junctions (NMJs) were identified with ␣-bungarotoxin. RESULTS. Ln␣2, the hallmark chain of skeletal muscle, and Ln2 were absent or partially absent from the BMs in a variable number of muscle fibers in most of the ALS EOMs. Three ALS donors showed dramatic decrease in the levels of these chains around their muscle fibers and NMJs. Changes in Ln␣2 were not age related and were also present in EOMs of ALS mouse models. Ln␣4 was preserved in the majority of NMJs in EOMs but absent in the majority of NMJs in limb muscle of ALS. The BMs around muscle fibers, NMJs, nerves, and blood vessels of the majority of EOMs of ALS donors had rather normal appearance and laminin composition, but heterogeneity was observed among EOM samples of individual ALS donors and between ALS donors. CONCLUSIONS. The present study showed distinct impact of ALS on EOMs compared with limb muscles. The EOMs maintained a normal laminin composition in their NMJs, which may be instrumental for the fact that they are not typically affected in
European Journal of Neurology, Mar 26, 2018
Background and purposeNemaline myopathy (NEM) has been associated with mutations in 12 genes to d... more Background and purposeNemaline myopathy (NEM) has been associated with mutations in 12 genes to date. However, for some patients diagnosed with NEM, definitive mutations are not identified in the known genes, suggesting that there are other genes involved. This study describes compound heterozygosity for rare variants in ryanodine receptor type 3 (RYR3) gene in one such patient.Methods and resultsClinical examination of the patient at 22 years of age revealed a long narrow face, high arched palate and bilateral facial weakness. She had proximal weakness in all four limbs, mild scapular winging but no scoliosis. Muscle biopsy revealed wide variation in fibre size with type 1 fibre predominance and atrophy. Abundant nemaline bodies were located in perinuclear and subsarcolemmal areas, and within the cytoplasm. No likely pathogenic mutations in known NEM genes were identified. Copy number variation in known NEM genes was excluded by NEM‐targeted comparative genomic hybridization array. Next‐generation sequencing revealed compound heterozygous missense variants in the RYR3 gene. RYR3 transcripts are expressed in human fetal and adult skeletal muscle as well as in human brain and cauda equina samples. Immunofluorescence of human skeletal muscle revealed a ‘single‐row’ appearance of RYR3, interspersed between the ‘double rows’ of ryanodine receptor type 1 (RYR1) at each A–I junction.ConclusionThe results suggest that variants in RYR3 may cause a recessive muscle disease with pathological features including nemaline bodies. We characterize the expression pattern of RYR3 in human skeletal muscle and brain, and the subcellular localization of RYR1 and RYR3 in human skeletal muscle.
Investigative Ophthalmology & Visual Science, Apr 28, 2009
Satellite cells and other muscle progenitor cells in extraocular muscles and limb muscles of ALS ... more Satellite cells and other muscle progenitor cells in extraocular muscles and limb muscles of ALS donors
Acta Ophthalmologica, Nov 29, 2017
To report a case of Exophiala phaeomuriformis mycotic keratitis in a patient from a subarctic cli... more To report a case of Exophiala phaeomuriformis mycotic keratitis in a patient from a subarctic climate region. Dematiaceous fungi (black yeasts) have been gaining importance as corneal keratitis and ulcer causative agents in certain regions, but no cases have been described in Scandinavia. Methods: Case report of a patient with a persistent corneal erosion that eventually presented a brown-pigmented infiltrate. The patient had a history of several months of topical therapy comprising medication for glaucoma, corticosteroids and antibiotics. A therapeutic contact lens was used, and amniotic membrane transplantation was performed before the development of the pigmented infiltrate. Results: Exophiala phaeomuriformis was identified on the microbiological cultures from the surgically obtained infiltrate scrapes. The patient responded to topical amphotericin and fluconazole, the erosion was cured and a stromal scar subsided. During follow-up, sequential slit-lamp images and anterior segment optical coherence tomography (OCT) scans were obtained. Conclusion: This is the first described case of keratitis caused by E. phaeomuriformis in a subarctic region, the first in Europe and, to our knowledge, the second reported case in the literature. It is important to remember that superficial corneal brown-pigmented infiltrates should raise the suspicion of an unusual fungal infection even in this climate. This is particularly important in patients with ocular surface disease treated with steroids and antibiotics for a long time.
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Papers by Fatima Domellof