| 1. |
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| 2. |
- Ali, Sara, et al.
(författare)
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Ocular Fundus Morphology and Visual Function in Adolescents Born Moderate-to-Late Preterm
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 64:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Previous studies have mostly focused on ophthalmological complications associated with being born extremely preterm despite that moderate-to-late preterm (MLP) account for 85% of all preterm births. The aim was to examine fundus morphology and visual function in adolescents born MLP, in comparison with controls born full-term.Methods: A prospective population-based cohort study of 247 MLP individuals (110 girls, gestational age 32-36 weeks) with no syndromes or history of retinopathy of prematurity participated in a neonatal study in 2002-2004. Later on, they have been included in ophthalmological follow-up studies at age 8 (n=50) and 12 (n=22). In the present study, 50 adolescents (26 girls; mean age 16.5 years) were examined regarding best corrected visual acuity (BCVA), refraction, and ocular morphology, measured by optical coherence tomography (Topcon, Japan). A group of 50 adolescents (30 girls, mean age 16.7 years) born full-term served as controls. Participants with refraction outside +/-6 diopters were excluded. T-test was used for statistical analysis.Results: The MLP-group (n=48) showed a thinner macular retinal nerve fibre layer (RNFL) inner mean in right eye (RE) (26.4±1.5 vs 27.1±1.7 μm; p=0.029) and in left eye (LE) (26.3±1.5 vs 27.0±1.5 μm; p=0.022) compared with controls. A thinner macular RNFL outer mean was found both in RE (40.2±4.4 vs 42.6±4.2 μm; p=0.011) and LE (40.3±4.0 vs 42.1±4.3 μm; p=0.034) (Fig.1A-B). A thicker central macular retinal thickness (MRT) (249.3±20.9 vs 239.9±16.4 μm; p=0.016) and a thinner total peripapillary (pp)RNFL (104.8±8.8 vs 109.1±8.3 μm; p=0.027) were found in RE. The BCVA in best eye was lower in the MLP-group (n=50) compared with controls (-0.09±0.08 vs -0.12±0.09 logMAR; p=0.022). At age 8, MLP births showed a thinner total macular volume and a thicker foveal minimum, central MRT, and central macular RNFL in RE. At age 12, a thicker foveal minimum and thinner outer macular RNFL were found in LE.Conclusions: MLP-birth may be associated with ophthalmological macular and ppRNFL changes as well as lower BCVA in adolescence. Similar morphology findings have been shown at younger ages, thus the fundus results persist into young adulthood.
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| 3. |
- Ali, Zaheer, et al.
(författare)
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Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 61:2
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood. In this study, pdx1 mutants were examined for retinal vascular and neuronal pathology to demonstrate suitability of these fish for modeling DR. METHODS. Vessel morphology was examined in pdx1 mutant and control fish expressing the fli1a:EGFP transgene. We further characterized vascular and retinal phenotypes in mutants and controls using immunohistochemistry, histology, and electron microscopy. Retinal function was assessed using electroretinography. RESULTS. Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness. CONCLUSIONS. This study highlights pdx1 mutant zebrafish as a valuable complement to rodent and other mammalian models of DR, in particular for research into the mechanistic interplay of diabetes with vascular and neuroretinal disease. They are furthermore suited for molecular studies to identify new targets for treatment of early as well as late DR.
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| 4. |
- Behzadi, Arvin, et al.
(författare)
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Myofiber type shift in extraocular muscles in amyotrophic lateral sclerosis
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 64:5
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate changes in myofiber composition in the global layer (GL) and orbital layer (OL) of extraocular muscles (EOMs) from terminal amyotrophic lateral sclerosis (ALS) donors.Methods: Medial recti muscles collected postmortem from spinal-onset ALS, bulbar-onset ALS, and healthy control donors were processed for immunofluorescence with antibodies against myosin heavy chain (MyHC) IIa, MyHCI, MyHCeom, laminin, neurofilaments, synaptophysin, acetylcholine receptor γ-subunit, and α-bungarotoxin.Results: The proportion of myofibers containing MyHCIIa was significantly smaller and MyHCeom was significantly larger in the GL of spinal-onset ALS and bulbar-onset ALS donors compared to control donors. Changes in the GL were more prominent in the bulbar-onset ALS donors, with a significantly larger proportion of myofibers containing MyHCeom being present compared to spinal-onset ALS donors. There were no significant differences in the myofiber composition in the OL. In the spinal-onset ALS donors, the proportions of myofibers containing MyHCIIa in the GL and MyHCeom in the OL were significantly correlated with the disease duration. Neurofilament and synaptophysin were present at motor endplates of myofibers containing MyHCeom in ALS donors.Conclusions: The EOMs of terminal ALS donors displayed changes in the fast-type myofiber composition in the GL, with a more pronounced alteration in bulbar-onset ALS donors. Our results align with the worse prognosis and subclinical changes in eye movement function previously observed in bulbar-onset ALS patients and suggest that the myofibers in the OL might be more resistant to the pathological process in ALS.
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| 5. |
- Burstedt, Marie, et al.
(författare)
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Retinal dystrophy associated with RLBP1 retinitis pigmentosa : a five-year prospective natural history study
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 64:13
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess the progression in functional and structural measures over a five-year period in patients with retinal dystrophy caused by RLBP1 gene mutation.Methods: This prospective, noninterventional study included patients with biallelic RLBP1 mutations from two clinical sites in Sweden and Canada. Key assessments included ocular examinations, visual functional measures (best-corrected visual acuity [BCVA], contrast sensitivity [CS], dark-adaptation [DA] kinetics up to six hours for two wavelengths [450 and 632 nm], Humphrey visual fields [HVF], full-field flicker electroretinograms), and structural ocular assessments.Results: Of the 45 patients enrolled, 38 completed the full five years of follow-up. At baseline, patients had BCVA ranging from -0.2 to 1.3 logMAR, poor CS, HVF defects, and prominent thinning in central foveal thickness. All patients had extremely prolonged DA rod recovery of approximately six hours at both wavelengths. The test-retest repeatability was high across all anatomic and functional endpoints. Cross-sectionally, poorer VA was associated with older age (right eye, correlation coefficient [CC]: 0.606; left eye, CC: -0.578; P < 0.001) and HVF MD values decreased with age (right eye, CC: -0.672, left eye, CC: -0.654; P < 0.001). However, no major changes in functional or structural measures were noted longitudinally over the five-year period.Conclusions: This natural history study, which is the first study to monitor patients with RLBP1 RD for five years, showed that severely delayed DA sensitivity recovery, a characteristic feature of this disease, was observed in all patients across all age groups (17-69 years), making it a potentially suitable efficacy assessment for gene therapy treatment in this patient population.
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| 6. |
- Börjeson, Charlie, et al.
(författare)
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Design of a compact open-field wavefront sensor
- 2021
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 62:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Casslén, Beatrice, et al.
(författare)
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Health-related quality of life and functional vision in individuals with retinoblastoma treated with ocular prothesis
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 64:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Health-Related Quality of Life (HR-QoL) among enucleated retinoblastoma (RB) survivors is scarcely studied. Perceptual Visual Dysfunctions (PVDs) are problems concerning interpretation of visual input, that to our knowledge, previously not has been studied in RB patients. This prospective cross-sectional cohort study aim to evaluate HR-QoL and PVDs in RB individuals, treated with ocular prosthesis.Methods: Twenty-seven RB individuals were treated with ocular prosthesis at the Sahlgrenska University Hospital, Gothenburg, Sweden, between 2000-2019. All were invited to the study, 15 (10 females; mean age 15.6 years, range 6.8-27.0 years) accepted. HR-QoL was assessed using the Pediatric Quality of Life inventory (PedsQL) with patients self- and parents-proxy report. Results were compared to normative data. PVDs was examined by history taking covering five areas and results were compared with a healthy, age- and sex- matched control group. Best corrected visual acuity (BCVA) was measured.Results: No differences were found in HR-QoL of individuals with RB compared with healthy controls, between parent proxy compared with parents of healthy children or between individuals with RB and their corresponding parents. More individuals with RB (9/15) reported PVDs in one or more areas (median 1; range 1-4) compared with 1/15 healthy controls; p=0.005 (Fig. 1). Depth perception was the most frequent reported PVD area (n=6), followed by simultaneous perception (n=5), movement (n=2), recognition (n=1) and orientation (n=1). Better HR-QoL correlated with better BCVA (r = -0.68; p=0.01) and fewer affected PVD areas (r = -0.63; p=0.01).Conclusions: The results showed no difference in HR-QoL of the RB individuals or parent-proxy compared with healthy controls. However, enucleated RB survivors were more affected by PVDs than healthy individuals. Their HR-QoL can be negatively affected by having problems within several PVD areas, and BCVA comprise an important role in QoL. It is necessary to identify PVDs to promote the best health care in individuals with RB treated with ocular prothesis. Further research is needed to better understand the impact on QoL and the role of PVDs among these individuals.
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| 8. |
- Dankis, Martin, et al.
(författare)
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Acute inhibitory effects of antidepressants on lacrimal gland secretion in the anesthetized rat
- 2021
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 62:7
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Patients that medicate with antidepressants commonly report dryness of eyes. The cause is often attributed to the anticholinergic properties of the drugs. However, regulation of tear production includes a substantial reflex-evoked component and is regulated via distinct centers in the brain. Further, the anticholinergic component varies greatly among antidepressants with different mechanisms of action. In the current study it was wondered if acute administration of antidepressants can disturb production of tears by affecting the afferent and/or central pathway. METHODS. Tear production was examined in vivo in anesthetized rats in the presence or absence of the tricyclic antidepressant (TCA) clomipramine or the selective serotonin reuptake inhibitor (SSRI) escitalopram. The reflex-evoked production of tears was measured by challenging the surface of the eye with menthol (0.1 mM) and cholinergic regulation was examined by intravenous injection with the nonselective muscarinic agonist methacholine (1–5 μg/kg). RESULTS. Acute administration of clomipramine significantly attenuated both reflex-evoked and methacholine-induced tear production. However, escitalopram only attenuated reflex-evoked tear production, while methacholine-induced production of tears remained unaffected. CONCLUSIONS. This study shows that antidepressants with different mechanisms of action can impair tear production by attenuating reflex-evoked signaling. Further, antimuscarinic actions are verified as a likely cause of lacrimal gland hyposecretion in regard to clomipramine but not escitalopram. Future studies on antidepressants with different selectivity profiles and mechanisms of action are required to further elucidate the mechanisms by which antidepressants affect tear production. Copyright 2021 The Authors
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| 9. |
- Domellöf, Fatima Pedrosa, et al.
(författare)
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The cytoskeleton of myotendinous junctions in human extraocular muscles
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To systematically investigate the composition of the cytoskeleton of the myotendinous junctions (MTJs) in human extraocular muscles (EOMs).Methods: Ten human EOM samples collected with ethical permission were processed for immunofluorescence with antibodies against the cytoskeletal proteins desmin, nestin, vimentin and cytokeratin 19; various myosin heavy chain (MyHC) isoforms as well as antibodies against tenascin or laminin to identify the MTJs.Results: The majority of the MTJs in both orbital and global layer contained desmin but an important proportion of them did not show increased levels of immunostaining at the folds of the MTJ, in contrast to other muscles. Desmin was absent from approximately 15% of the MTJs and mostly in myofibers containing MyHCIIa. Nestin was present in approximately 91% of the MTJs. Four different combinations were encountered regarding immunolabeling for desmin+nestin at the MTJs, including absence of both in a subgroup of MTJs, irrespective of fiber type. Vimentin was not present at the MTJs and cytokeratin 19 was either present or absent from the MTJs.Conclusions: The present data on the composition of the cytoskeleton at the MTJs in the EOMs raises fundamental questions regarding our previous knowledge on the role of these proteins for force transmission. We propose a novel model to further investigate these questions.
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| 10. |
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| 11. |
- Gustavsson, Simon T., et al.
(författare)
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Nicotinamide prevents retinal vascular dropout in a rat model of ocular hypertension and supports ocular blood supply in glaucoma patients
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 64
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate whether nicotinamide (NAM) modulates retinal vasculature in glaucoma.METHODS. This was a prospective controlled clinical trial investigating animal and human histopathology. Participants included normotensive and ocular hypertensive rats, postmortem human ocular tissue, glaucoma patients (n = 90), and healthy controls (n = 30). The study utilized histopathology, computer-assisted retinal vasculature analysis, optical coherence tomography angiography (OCTA), and NAM treatment. The main outcome measures included retinal vascular parameters in rats as assessed by AngioTool; retinal vasculature integrity in rats and humans as assessed by histopathology, antibody-staining, and ImageJ-based measurements; and retinal perfusion density (PD) and flux index in humans as assessed by OCTA.RESULTS. A number of vessel parameters were altered in ocular hypertension/glaucoma compared to healthy controls. NAM treatment improved the retinal vasculature in ocular hypertensive rats, with an increase in mean vessel area, percentage area covered by vessels, total vessel length, total junctions, and junction density as assessed by AngioTool (all P < 0.05); vessel wall integrity as assessed by VE-cadherin antibody staining was also improved (P < 0.01). In humans, as assessed by OCTA, increases in PD in the optic nerve head and macula complete image (0.7%, P = 0.04 and 1.0%, P = 0.002, respectively) in healthy controls, and an increase in the temporal quadrant of the macula (0.7%, P = 0.02) in glaucoma patients was seen after NAM treatment.CONCLUSIONS. NAM can prevent retinal vascular damage in an animal model of glaucoma. After NAM treatment, glaucoma patients and healthy controls demonstrated a small increase in retinal vessel parameters as assessed by OCTA.
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| 12. |
- Herold, Janina M., et al.
(författare)
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Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 64:12
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD.Methods: In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg), we graded AMD via color fundus images applying two established classification systems (CC and 3CACSS). We calculated the genetic risk score (GRS) across 50 previously identified variants for late AMD, its association via logistic regression, and area under the curve (AUC) for each AMD stage.Results: We analyzed 2188 persons aged 70 to 95 years. When comparing the two classification systems, we found a distinct pattern: CC “age-related changes” and CC “early AMD” distinguished individuals with 3CACSS “no AMD”; 3CACSS “mild/moderate/severe early AMD” stages, and distinguished CC “intermediate AMD”. This suggested a 7-step scale combining the 2 systems: (i) “no AMD”, (ii) “age-related changes”, (iii) “very early AMD”, (i.e. CC “early”), (iv) “mild early AMD”, (v) “moderate early AMD”, (vi) “severe early AMD”, and (vii) “late AMD”. GRS association and diagnostic accuracy increased stepwise by increased AMD severity in the 7-step scale and by increased restriction of controls (e.g. for CC “no AMD without age-related changes”: AUC = 55.1%, 95% confidence interval [CI] = 51.6, 58.6, AUC = 62.3%, 95% CI = 59.1, 65.6, AUC = 63.8%, 95% CI = 59.3, 68.3, AUC = 78.1%, 95% CI = 73.6, 82.5, AUC = 82.2%, 95% CI = 78.4, 86.0, and AUC = 79.2%, 95% CI = 75.4, 83.0). A stepwise increase was also observed by increased drusen size and area.Conclusions: The utility of a 7-step scale is supported by our clinical and GRS data. This harmonization and full data integration provides an immediate simplification over using either CC or 3CACSS and helps to sharpen the control group.
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| 13. |
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| 14. |
- Holmlund, Petter, 1988-, et al.
(författare)
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Posture-dependent collapse of the optic nerve subarachnoid space : A combined MRI and modeling study
- 2021
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We hypothesize that a collapse of the optic nerve subarachnoid space (ONSAS) in the upright posture may protect the eyes from large translamina cribrosa pressure differences (TLCPD) believed to play a role in various optic nerve diseases (e.g., glaucoma). In this study, we combined magnetic resonance imaging (MRI) and mathematical modeling to investigate this potential ONSAS collapse and its effects on the TLCPD.METHODS: First, we performed MRI on six healthy volunteers in 6° head-down tilt (HDT) and 13° head-up tilt (HUT) to assess changes in ONSAS volume (measured from the eye to the optic canal) with changes in posture. The volume change reflects optic nerve sheath (ONS) distensibility. Second, we used the MRI data and mathematical modeling to simulate ONSAS pressure and the potential ONSAS collapse in a 90° upright posture.RESULTS: The MRI showed a 33% decrease in ONSAS volume from the HDT to HUT (P < 0.001). In the upright posture, the simulations predicted an ONSAS collapse 25 mm behind lamina cribrosa, disrupting the pressure communication between the ONSAS and the intracranial subarachnoid space. The collapse reduced the simulated postural increase in TLCPD by roughly 1 mm Hg, although this reduction was highly sensitive to ONS distensibility, varying between 0 and 4.8 mm Hg when varying the distensibility by ± 1 SD.CONCLUSIONS: The ONSAS volume along the optic nerve is posture dependent. The simulations supported the hypothesized ONSAS collapse in the upright posture and showed that even small changes in ONS stiffness/distensibility may affect the TLCPD.
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| 15. |
- Huang, X. F., et al.
(författare)
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Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci
- 2020
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:6
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B 27 , implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. METHODS. We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available alter SNP microarray genotyping, imputation, and quality-control filtering. RESULTS. We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 x 10(-8), odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 x 10(-7), OR = 1.22) and NOS2 (rs2274894, P = 8.22 x 10(-7), OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rsl0171979, P = 2.56 x 10(-6), OR = 1.20), KIFAP3 (rs508063, P = 5.64 x 10(-7), OR = 1.20), CLCN7 (rs67412457, P = 1.33 x 10(-6), OR = 1.25), ACAA2 (rs9947182, P = 9.70 x 10(-7), OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. CONCLUSIONS. We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.
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| 16. |
- Jóhannesson, Gauti, 1979-, et al.
(författare)
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Intraocular Pressure Decrease Does Not Affect Blood Flow Rate of Ophthalmic Artery in Ocular Hypertension
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 61:12
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate if decrease of IOP affects the volumetric blood flow rate in the ophthalmic artery (OA) in patients with previously untreated ocular hypertension.METHODS: Subjects with untreated ocular hypertension (n = 30; mean age 67 +/- 8 years; 14 females) underwent ophthalmologic examination and a 3-Tesla magnetic resonance imaging investigation. The magnetic resonance imaging included three-dimensional high-resolution phase-contrast magnetic resonance imaging to measure the OA blood flow rate. The subjects received latanoprost once daily in the eye with higher pressure, the untreated eye served as control. The same measurements were repeated approximately 1 week later.RESULTS: The mean OA blood flow rate before and after treatment was 12.4 +/- 4.4 and 12.4 +/- 4.6 mL/min in the treated eye (mean +/- SD; P = 0.92) and 13.5 +/- 5.2 and 13.4 +/- 4.1 mL/min in the control eye (P = 0.92). There was no significant difference between the treated and control eye regarding blood flow rate before (P = 0.13) or after treatment (P = 0.18), or change in blood flow rate after treatment (0.1 +/- 3.1 vs.-0.1 +/- 4.0 mL/min, P = 0.84). Latanoprost decreased the IOP by 7.2 +/- 3.1 mm Hg in the treated eye (P < 0.01).CONCLUSIONS: The results indicate that a significant lowering of IOP does not affect the blood flow rate of the OA in ocular hypertension subjects. The ability to maintain blood supply to the eye independent of the IOP could be a protective mechanism in preserving vision in subjects with ocular hypertension.
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| 17. |
- Kahsay, Abraha, et al.
(författare)
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Obscurin maintains myofiber identity in extraocular muscles
- 2024
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 65:2
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The cytoskeleton of the extraocular muscles (EOMs) is significantly different from that of other muscles. We aimed to investigate the role of obscurin, a fundamental cytoskeletal protein, in the EOMs.Methods: The distribution of obscurin in human and zebrafish EOMs was compared using immunohistochemistry. The two obscurin genes in zebrafish, obscna and obscnb, were knocked out using CRISPR/Cas9, and the EOMs were investigated using immunohistochemistry, qPCR, and in situ hybridization. The optokinetic reflex (OKR) in five-day-old larvae and adult obscna−/−;obscnb−/− and sibling control zebrafish was analyzed. Swimming distance was recorded at the same age.Results: The obscurin distribution pattern was similar in human and zebrafish EOMs. The proportion of slow and fast myofibers was reduced in obscna−/−;obscnb−/− zebrafish EOMs but not in trunk muscle, whereas the number of myofibers containing cardiac myosin myh7 was significantly increased in EOMs of obscurin double mutants. Loss of obscurin resulted in less OKRs in zebrafish larvae but not in adult zebrafish.Conclusions: Obscurin expression is conserved in normal human and zebrafish EOMs. Loss of obscurin induces a myofiber type shift in the EOMs, with upregulation of cardiac myosin heavy chain, myh7, showing an adaptation strategy in EOMs. Our model will facilitate further studies in conditions related to obscurin.
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| 18. |
- Karjosukarso, Dyah W., et al.
(författare)
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Modeling ZNF408-Associated FEVR in Zebrafish Results in Abnormal Retinal Vasculature
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 61:2
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disease in which the retinal vasculature is affected. Patients with FEVR typically lack or have abnormal vasculature in the peripheral retina, the outcome of which can range from mild visual impairment to complete blindness. A missense mutation (p.His455Tyr) in ZNF408 was identified in an autosomal dominant FEVR family. Little, however, is known about the molecular role of ZNF408 and how its defect leads to the clinical features of FEVR. METHODS. Using CRISPR/Cas9 technology, two homozygous mutant zebrafish models with truncated znf408 were generated, as well as one heterozygous and one homozygous missense znf408 model in which the human p.His455Tyr mutation is mimicked. RESULTS. Intriguingly, all three znf408-mutant zebrafish strains demonstrated progressive retinal vascular pathology, initially characterized by a deficient hyaloid vessel development at 5 days postfertilization (dpf) leading to vascular insufficiency in the retina. The generation of stable mutant lines allowed long-term follow up studies, which showed ectopic retinal vascular hyper-sprouting at 90 dpf and extensive vascular leakage at 180 dpf. CONCLUSIONS. Together, our data demonstrate an important role for znf408 in the development and maintenance of the vascular system within the retina.
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| 19. |
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| 20. |
- Kim, Jihye, et al.
(författare)
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Association of coffee, tea, and caffeine consumption with intraocular pressure and interaction with genetic risk : findings from the UK Biobank
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 61:7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose : Coffee and tea are commonly consumed caffeinated beverages that may affect ocular health. Hence, it is of interest whether caffeine intake affects intraocular pressure (IOP). Some studies reported that coffee and caffeine consumption is associated with higher IOP. However, evidence from large-scale general population studies is limited. Methods : We included 121,755 UK Biobank participants (aged 39-73y) who had dietary data and cornea-compensated IOP measurements in 2006-2010. In a subset (n=78,017), data were available from up to five web-based 24-hour-recall food frequency questionnaires (2009-2012); we derived participants’ total caffeine consumption based on caffeine content and frequency of caffeine-containing food intake. Using multivariable linear regression, we assessed the cross-sectional relationships between coffee or tea intake (cups/day) and IOP (mmHg) as primary analyses and the associations between total caffeine intake (80 mg/day) and IOP (mmHg) as secondary analyses. Analyses were adjusted for age, sex, ethnicity, smoking, alcohol intake, physical activity, deprivation, body mass index, blood pressure, and diabetes (and total energy intake in the subset). To explore gene-diet interactions, we examined interactions between coffee, tea, caffeine intake and an IOP polygenic risk score (PRS) combining effects of 111 genetic variants associated with IOP identified by genome-wide association studies. Results : Mean (SD) IOP was 16.0 (3.8) mmHg. Higher coffee, tea, and total caffeine intakes were associated with lower IOP (-0.049, -0.045 and -0.039 mmHg, respectively; P ≤ 0.001). When evaluating PRS-diet interactions, we found positive and significant interactions with tea and caffeine intake (both P-interactions < 0.05), where higher tea and caffeine intake was associated with lower IOP among individuals with IOP PRS in the lower 75th percentile, while among individuals with high IOP PRS (top 25th percentile), higher intakes were associated with modestly higher IOP. Conclusions : We found evidence for very weak associations between higher coffee, tea and caffeine intake and lower IOP. However, our finding on gene-diet interactions suggest that genetic predisposition to higher IOP may influence the association between caffeinated beverage consumption and IOP.
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| 23. |
- Kristiansen, Martin, et al.
(författare)
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Optic nerve subarachnoid space posture dependency : an MRI study in subjects with normal tension glaucoma and healthy controls
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 64:15
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to examine the differences of optic nerve subarachnoid space (ONSAS) volume in patients with normal tension glaucoma (NTG) and healthy controls in different body positions.Methods: Eight patients with NTG and seven healthy controls underwent magnetic resonance imaging (MRI) examinations in head up tilt (HUT) +11 degrees and head down tilt (HDT) -5 degrees positions according to a randomized protocol determining the starting position. The ONSAS volume in both body positions was measured and compared between the two groups. The results were analyzed using a generalized linear model.Results: Between HDT and HUT, the postural ONSAS volume change was dependent on starting position (P < 0.001) and group (P = 0.003, NTG versus healthy). A subgroup analysis of those that were randomized to HUT examination first, coming directly from an upright position, showed that the patients with NTG had significantly larger positional ONSAS volume changes compared to the healthy controls; 121 ± 22 µL vs. 65 ± 37 µL (P = 0.049). Analysis of the ONSAS volume distribution showed different profiles for patients with NTG and healthy controls.Conclusions: There was a significant difference in ONSAS volume change between patients with NTG and healthy subjects when subjected to posture changes, specifically when going from upright to head-down posture. This indicates that patients with NTG had been exposed to a lower ONSAS pressure when they came from the upright posture, which suggests an increased translaminar pressure difference in upright position. This may support the theory that NTG has a dysfunction in an occlusion mechanism of the optic nerve sheath that could cause abnormally negative ONSAS pressures in upright posture.
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| 24. |
- Lind, Alexandra, et al.
(författare)
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Ocular Dimensions in Relation to Growth and Metabolic Factors in Adolescents Born Moderate-to-Late Preterm
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 64:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: The majority of all preterm birth are moderate-to-late preterm (MLP) birth, defined as birth at 32–36 weeks of gestation. These individuals have an elevated morbidity risk compared with full-term individuals; however, little is known of the ocular development. The purpose of the present study was to evaluate ocular dimensions in relation to growth and metabolic factors in MLP adolescents.Methods: In this prospective cohort study, 50 MLP adolescents participated (26 girls; mean gestational age 35.0 weeks; mean age 16.5 years). When recruited at birth, the exclusion criteria were chromosomal abnormalities, severe malformations, syndromes, or being born to mothers with chronic diseases. A control group consisted of 50 adolescents born full-term (30 girls; 40.3 weeks; 16.7 years). Total axial length (TAL), palpebral fissure length (PFL), and intercanthal distance (ICD) were measured. The TAL was evaluated using optical biometry (IOL Master). The PFL and ICD were measured using a ruler. Head circumference, length, weight, body mass index, and serum levels of insulin-like growth factor I and insulin-like growth factor binding protein 3 were evaluated. Serum levels of the metabolic factors leptin and adiponectin were measured. The MLP and control group were compared regarding all variables using Mann Whitney U-test. Ocular dimensions were analyzed to find any possible association with growth and metabolic factors using Spearman rank correlation.Results: The MLP group had shorter TAL and PFL, and wider ICD compared with controls, shown in Table 1. There was no significant difference regarding growth, leptin, or adiponectin. Within the MLP group, TAL correlated with length (right eye (RE) r=0.46, p<0.001; left eye (LE) r=0.48, p<0.001), head circumference (RE r=0.46, p<0.001; LE r=0.44, p=0.001), and weight (RE r=0.53, p<0.001; LE r=0.51, p<0.001). The PFL correlated with length (RE r=0.53, p<0.001; LE r=0.58, p<0.001), and leptin (RE r=-0.43, p=0.004; LE r=-0.46, p=0.002). No other significant correlation was found.Conclusions: In the present study, being born MLP were shown to impact ocular growth including TAL, PFL, and ICD. Furthermore, these variables were found to be associated with leptin levels and general growth.
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| 25. |
- Liu, Jing-Xia, et al.
(författare)
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Complex Correlations Between Desmin Content, Myofiber Types, and Innervation Patterns in the Human Extraocular Muscles
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology, Inc. (ARVO). - 0146-0404 .- 1552-5783. ; 61:3
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate whether the distribution of intermediate filament protein desmin is related to the different patterns of innervation in the human extraocular muscles (EOMs).METHODS. EOM samples were analyzed with immunohistochemistry using antibodies against desmin, vimentin, different myosin heavy chain (MyHC) isoforms, and fetal and adult acetylcholine receptor (AChR) subunits. Neuromuscular junctions (NMJs) were identified with alpha-bungarotoxin or with antibodies against neurofilament and synaptophysin.RESULTS. Desmin was present in the vast majority of myofibers, but it was weakly present or absent in a limited area in the close vicinity of the single en plaque NMJs in less than half of these myofibers. Desmin was either present or lacking in MyHCsto/I myofibers displaying multiple en grappe endings but present in MyHCsto/I myofibers receiving spiral nerve endings. In MyHCeom myofibers displaying multiterminal en plaque endings, desmin was either present or absent irrespective of AChR subunits or EOM layer. Vimentin did not substitute for the lack of desmin.CONCLUSIONS. The results indicate that the human EOMs have a more complex cytoskeletal organization than other muscles and suggest additional signalling mechanisms from the NMJs to the myofibers.
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| 26. |
- Liu, Jing-Xia, et al.
(författare)
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Cytoskeletal Proteins in Myotendinous Junctions of Human Extraocular Muscles
- 2021
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Ingår i: Investigative Ophthalmology and Visual Science. - : ARVO journals. - 0146-0404 .- 1552-5783. ; 62:2, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to investigate the cytoskeletal composition of myotendinous junctions (MTJs) in the human extraocular muscles (EOMs). Desmin and other major cytoskeletal proteins are enriched at the MTJs of ordinary myofibers, where they are proposed to be of particular importance for force transmission and required to maintain myofiber integrity. Methods: EOM and limb muscle samples were analyzed with immunohistochemistry using antibodies against the intermediate filament proteins desmin, nestin, keratin 19, vimentin, and different myosin heavy chain (MyHC) isoforms. MTJs were identified by labeling with antibodies against laminin or tenascin. Results: In contrast to MTJs in lumbrical muscle where desmin, nestin, and keratin 19 were always present, approximately one-third of the MTJs in the EOMs lacked either desmin and/or nestin, and all MTJs lacked keratin 19. Approximately 6% of the MTJs in the EOMs lacked all of these key cytoskeletal proteins. Conclusions: The cytoskeletal protein composition of MTJs in human EOMs differed significantly from that of MTJs in limb muscles. These differences in cytoskeletal protein composition may indicate particular adaptation to meet the functional requirements of the EOMs.
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| 27. |
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| 28. |
- Lundström, Linda, et al.
(författare)
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Peripheral optical errors and hazard perception
- 2021
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 62:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 29. |
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| 30. |
- Sagerfors, Susanna, 1977-, et al.
(författare)
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What targeted sequencing can tell us, that culture cannot : The corneal microbiome in infectious keratitis
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 64:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To describe the corneal microbiome in infectious keratitis in relation to contact lens wear or not, and culture outcome. To explore if targeted sequencing may provide information concerning: i) culture negative episodes, ii) variables influencing culture outcome of corneal samples dispensed in transport medium.Methods: Prospective inclusion of patients fulfilling predefined criteria of infectious keratitis. Corneal samples were dispensed in liquid Amies medium, from which both culture and targeted sequencing of the V3-V4 region of the 16S rRNA gene were carried out. Additional standard corneal culture was also performed. Main outcome measures were bacterial findings by targeted sequencing in relation to contact lens wear and culture outcome, and identification of variables influencing corneal culture outcome of indirectly inoculated corneal samples, using quantitative data from the PCR.Results: In all, 94 episodes of infectious keratitis were included, of which 70 (74%) had bacterial growth on corneal culture. In median, 15 (range 8-30) different bacterial genera per episode of infectious keratitis were detected by targeted sequencing. The contact lens wearers (69/94; 73%) displayed significant (p=0.01) differences in the bacterial community composition of the corneal lesion compared to non-wearers, with higher abundance of Staphylococcus spp. Corynebacterium spp. and Stenotrophomonas maltophilia. Among the culture negative episodes (n=24) Brevundimonas was found to be significantly (adjusted p<0.05) enriched. Sequencing detected a potential corneal pathogen such as Clostridium, Staphylococcus, Brevundimonas, Pseudomonas and Veillonella, with a relative abundance of at least 20% in more than half of the culture negative episodes (14/24; 58%). Bacterial density in the sample had the highest impact on culture outcome (OR 6.3; p=0.009) but also age increased the odds for a positive culture outcome (OR 1.04; p=0.034), while prior antibiotic treatment significantly reduced the odds of a positive corneal culture to a fifth (OR 0.2; p=0.031).Conclusions: Targeted sequencing can provide a potential corneal pathogen in case of a negative culture outcome in patients with infectious keratitis, as well as providing insights on the corneal microbiome of infectious keratitis and factors influencing its composition.
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| 31. |
- Sghari, Soufien, et al.
(författare)
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Elucidation of Cellular Mechanisms That Regulate the Sustained Contraction and Relaxation of the Mammalian Iris
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - Rockville : Association of Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 61:11
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. In mammals, pupil constriction and dilation form the pupillary light reflex (PLR), which is mediated by both brain-regulated (parasympathetic) and local iris-driven reflexes. To better understand the cellular mechanisms that regulate pupil physiological dynamics via central and local photoreception, we have examined the regulation of the PLR via parasympathetic and local activation, respectively.METHODS. In this study, the PLR was examined in mouse enucleated eyes ex vivo in real-time under different ionic conditions in response to acetylcholine and/or blue light (480 nm). The use of pupillometry recordings captured the relaxation, contraction, and pupil escape (redilation) processes for 10 minutes up to 1 hour.RESULTS. Among others, our results show that ryanodine receptor channels are the main driver for iridal stimulation-contraction coupling, in which extracellular influx of Ca2+ is required for amplification of pupil constriction. Both local and parasympathetic iridal activations are necessary, but not sufficient for sustained pupil constriction. Moreover, the degree of membrane potential repolarization in the dark is correlated with the latency and velocity of iridal constriction. Furthermore, pupil escape is driven by membrane potential hyperpolarization where voltage-gated potassium channels play a crucial role.CONCLUSIONS. Together, this study presents new mechanisms regulating synchronized pupil dilation and contraction, sustained pupil constriction, iridal stimulation-contraction coupling, and pupil escape.
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| 35. |
- Tosi, Gian Marco, et al.
(författare)
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The Binding of CD93 to Multimerin-2 Promotes Choroidal Neovascularization
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:8
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. The purpose of this study was to investigate the involvement of CD93 and Multimerin-2 in three choroidal neovascularization (CNV) models and to evaluate their contribution in the neovascular progression of age-related macular degeneration (AMD). METHODS. Choroidal neovascular membranes collected during surgery from AMD patients were analyzed by microscopy methods. Laser-induced CNV mouse models and choroid sprouting assays (CSAs) were carried out using the CD93 knockout mouse model. An original ex vivo CSA of vascular angiogenesis, employing choroid tissues isolated from human donors, was developed. RESULTS. In contrast to healthy choroid endothelium, hyperproliferative choroidal endothelial cells (ECs) of AMD patients expressed high levels of CD93, and Multimerin-2 was abundantly deposited along the choroidal neovasculature. CD93 knockout mice showed a significant reduced neovascularization after laser photocoagulation, and their choroidal ECs displayed a decreased ability to produce sprouts in ex vivo angiogenesis assays. Moreover, the presence of an antibody able to hamper the CD93/Multimerin-2 interaction reduced vascular sprouting in the human CSA. CONCLUSIONS. Our results demonstrate that CD93 and its interaction with Multimerin-2 play an important role in pathological vascularization of the choroid, disclosing new possibilities for therapeutic intervention to neovascular AMD.
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| 36. |
- Venkataraman, Abinaya Priya, 1985-, et al.
(författare)
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Impact of peripheral optical errors in AMD and healthy eyes
- 2021
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 62:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 37. |
- Wittich, Walter, et al.
(författare)
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Expert Survey for the Development of a Core Set for Deafblindness using the International Classification of Functioning, Disability, and Health
- 2023
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 64:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Individuals with deafblindness are a diverse group and require interdisciplinary care. To provide a universal terminology that facilitates communication among stakeholders, the World Health Organization (WHO) developed the International Classification of Functioning, Disability and Health (ICF). A sub-selection of categories, referred to as ICF Core Sets, provides a tool to describe functioning and disability in specific health conditions. As part of a multi-study process of developing a Core Set for deafblindness, we conducted an expert survey for the identification of key concepts.Methods: An international online survey gathered the opinion of professionals who worked with persons with deafblindness. Six open-ended questions addressed their perceptions on how deafblindness affects body functions and structures, activities, and participation, and how personal and environmental factors act as barriers and/or facilitators in everyday life with deafblindness. Survey responses were analysed using content analysis, and meaningful concepts were linked to the ICF codes using linking rules established by the WHO.Results: Of the 205 complete responses, 100 stratified respondents were selected across the WHO regions: Africa (n = 8), the Americas (n = 31), South-East Asia (n = 22), Europe (n = 25), Western Pacific (n = 14). Professions included optometry, ophthalmology, low vision therapy, occupational therapy, intervenor/interpreter, social work, rehabilitation counselling, O&M, and psychology, among others. The most frequent codes linked to body structures were eye, ear (s299), and nervous system (s1). Most prevalent body function codes included seeing (b210), hearing (b230), tactile perception (b1564) and touch (b265). For activity and participation, experts identified communication (d399), carrying out daily routine (d2309), and learning and applying knowledge (d199) as main concepts. Environmental variables focused on societal attitude (e460), human caused events (e235), light (240) and sounds (e250).Conclusions: The expert views that are not easily coded using the ICF were global effects of deafblindness that affect all aspects of functioning, as well as those that are progressive over time. Next, the ICF codes reported by at least 5% of the experts will be included in the list of candidate categories for an international consensus conference.
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| 41. |
- Dankis, Martin, et al.
(författare)
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Novel Insights Into Muscarinic and Purinergic Responses in Primary Cultures of Rat Lacrimal Gland Myoepithelial Cells.
- 2021
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Ingår i: Investigative ophthalmology & visual science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 62:12
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Tidskriftsartikel (refereegranskat)abstract
- The functional characteristics of receptors that regulate lacrimal gland myoepithelial cells are still somewhat unclear. To date, mainly muscarinic receptors have been of interest; however, further knowledge is needed regarding their expression and functional roles. For this purpose, primary cultures of rat lacrimal gland myoepithelial cells were established and examined functionally.Rat lacrimal glands were excised, minced, and further digested, yielding mixtures of cells that were seeded in culturing flasks. After 4-6 weeks, primary monocultures of myoepithelial cells were established, verified by immunocytochemistry. The cells were stained for all muscarinic receptor subtypes (M1-M5) and examined functionally regarding intracellular [Ca2+] responses upon activation of muscarinic receptors. For methodological verification, purinergic functional responses were also studied.Expression of muscarinic receptor subtypes M2-M5 was detected, whereas expression of muscarinic M1 receptors could not be shown. Activation of muscarinic receptors by the non-selective muscarinic agonist methacholine (3 × 10-11-10-3 M) did not cause a significant increase in intracellular [Ca2+]. However, activation of purinergic receptors by the non-selective purinergic agonist ATP (10-8-10-3 M) caused a concentration-dependent increase in intracellular [Ca2+] that could be blocked by the P2 antagonists PPADS and suramin.Primary cultures of rat lacrimal gland myoepithelial cells were established that displayed a heterogeneous expression of muscarinic receptors. Purinergic functional responses demonstrated a viable cell population. Upon treatment with methacholine, no significant increase in intracellular [Ca2+] could be detected, indicating that cholinergic activation of myoepithelial cells occurs via other intracellular messengers or is dependent on interaction with other cell types.
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