Significance
The increasing prevalence of myopia is a significant public health concern. Unfortunately, the mechanisms driving myopia remain elusive, limiting effective treatment options. This report ...identifies a refractive development pathway that requires
Opn5
-expressing retinal ganglion cells (RGCs). Stimulation of
Opn5
RGCs with short-wavelength violet light prevented experimental myopia in mice. Furthermore, this effect was dependent on the time of day, with evening exposure being sufficient to protect against experimental myopia. Thus, these studies suggest
Opn5
RGCs may contribute to the mechanisms of emmetropization and identify the OPN5 pathway as a potential target for the treatment of myopia.
Myopia has become a major public health concern, particularly across much of Asia. It has been shown in multiple studies that outdoor activity has a protective effect on myopia. Recent reports have shown that short-wavelength visible violet light is the component of sunlight that appears to play an important role in preventing myopia progression in mice, chicks, and humans. The mechanism underlying this effect has not been understood. Here, we show that violet light prevents lens defocus–induced myopia in mice. This violet light effect was dependent on both time of day and retinal expression of the violet light sensitive atypical opsin, neuropsin (OPN5). These findings identify
Opn5
-expressing retinal ganglion cells as crucial for emmetropization in mice and suggest a strategy for myopia prevention in humans.
Abstract Purpose To investigate the relationship between fluorescein breakup patterns (FBUPs) and clinical manifestations in dry-eye cases. Design Cross-sectional study. Methods In 106 eyes of 106 ...subjects (19 males, 87 females; mean age: 64.2 years), FBUPs were categorized into 1 of the following 5 break (B) types: area (AB, n=19); spot (SB, n=22); line (LB, n=24); dimple (DB, n=19); random (RB, n=22 eyes), and dry-eye-related symptoms using the visual analog scale (VAS, 100mm=maximum), tear meniscus radius (TMR, mm), tear-film lipid-layer interference grade (IG) (grades 1-5; 1=best) and spread grade (SG) (grades 1-4; 1=best), tear-film non-invasive breakup time (NIBUT, seconds), FBU time (FBUT, seconds), corneal-epithelial damage (CED) score (15 points=maximum), ocular-surface epithelial damage (OSED) score (9 points=maximum), and the Schirmer 1 test (ST1, mm) were examined and compared between each FBUP. Results In each FBUP, eye dryness and fatigue were the severest symptoms. Characteristic symptoms were sensitivity to light, heavy eyelids, pain, foreign-body sensation, difficulty opening the eye, and discharge for AB, heavy eyelids for SB, foreign-body sensation for LB. Statistically significant differences were found in TMR (AB-SB, -DB and -RB; LB-RB), IG (AB-all other FBUP; LB-SB and -DB), and SG (AB-all other FBUPs), FBUT (AB-LB, -DB, and –RB; SB-DB and –RB; LB-RB; DB-RB), and NIBUT (AB-all other FBUPs; SB-DB and-RB, and LB-RB), CED (AB-all other FBUPs; LB-SB, -DB, and -RB) and OSED (AB-SB, -LB, and -DB; LB-SB, -DB, and -RB), and ST1 (AB-SB, -DB, and -LB) (p<0.05 in each comparison). Conclusions The 5 different FBUPs constituted different groups, reflecting different pathophysiologies.
Interferons and Dry Eye in Sjögren's Syndrome Ogawa, Yoko; Shimizu, Eisuke; Tsubota, Kazuo
International journal of molecular sciences,
11/2018, Letnik:
19, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Various cytokines, including interferon (IFN)-γ and IL-17, are augmented, and autoreactive T cells and B cells are activated in the immune pathogenesis of Sjögren's syndrome (SS). In particular, IFNs ...are involved in both the early stages of innate immunity by high level of type I IFN in glandular tissue and sera and the later stages of disease progression by type I and type II IFN producing T cells and B cells through B cell activating factor in SS. Genetically modified mouse models for some of these molecules have been reported and will be discussed in this review. New findings from human SS and animal models of SS have elucidated some of the mechanisms underlying SS-related dry eye. We will discuss IFN-γ and several other molecules that represent candidate targets for treating inflammation in SS-related dry eye.
To evaluate the long-term outcome of cultivated oral mucosal epithelial transplantation (COMET) in treatment of eyes with total limbal stem cell deficiency.
Noncomparative, retrospective, ...interventional case series.
Forty eyes in 36 patients with total limbal stem cell deficiency (Stevens-Johnson syndrome in 12 eyes, chemical or thermal burns in 11 eyes, ocular cicatricial pemphigoid OCP in 9 eyes, pseudo-OCP in 7 eyes, and gelatinous drop-like dystrophy in 1 eye) were treated at the Department of Ophthalmology, Tokyo Dental College, Chiba, Japan.
Cultivated autologous oral mucosal epithelial sheets were transplanted onto the ocular surface in eyes with total limbal stem cell deficiency.
Reconstruction of a stable ocular surface with a clear appearance and no epithelial defects, reduction in fibrovascular tissue invasion of corneal surface, a functional fornix, change in visual acuity, and postoperative complications.
The mean follow-up period was 25.5 months (range, 6-54.9 months). Kaplan-Meier analysis of a corneal surface stability revealed an early decline in transplanted oral mucosal epithelial stability over the first 6 months, remaining comparatively stable thereafter (1 year, 64.8%; 2 years, 59.0%; and 3 years, 53.1%). Postoperative persistent epithelial failure developed within the first 3 months in 9 eyes. Early epithelial failure was associated closely with preoperative corneal defects. Gradual fibrovascular tissue invasion of the corneal surface was observed in 8 eyes and was marked in cases of OCP. Survival of a functional fornix decreased progressively until approximately 6 months. Postoperative visual acuity seemed to be related to the presence of corneal opacity. Complications included stromal melting or perforation in 8 eyes, infectious keratitis in 2 eyes, glaucoma in 8 eyes, and recurrence of herpetic keratitis in 1 eye. Corneal melting or perforation and infectious keratitis were associated closely with persistent epithelial defects after COMET.
The transplantation of cultivated oral mucosal epithelial sheets offers a viable and safe alternative in the reconstruction of a stable ocular surface. Epithelialization of the corneal surface is very important not only in obtaining a satisfactory long-term outcome, but also in achieving a lower incidence of complications.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
The autonomic nervous system plays a crucial role in the maintenance of homeostasis. Neurogenic inflammation due to decreased stability of tear film may induce changes in autonomic nerve activity, ...which could be associated with symptom expression.This study aimed to measure biological parameters that represent autonomic nerve activity in dry eye (DE)s caused by tear film dysfunction and investigate their relationship with symptom intensity. This prospective, cross-sectional, comparative study evaluated 34 eyes of 34 participants (mean age: 52.5 ± 13.4 years; range: 20–81 years) without keratoconjunctival damage. Nineteen eyes in the DE group showed DE symptoms and tear break-up time (TBUT) of ≤5 seconds (short TBUT DE); the 15 eyes in the non-DE group showed no DE symptoms. Autonomic nerve activity was measured for 10 minutes—starting and ending 5 minutes before and after instilling ophthalmic solution—and evaluated using the low-frequency component (LF) to the high-frequency component (HF) ratio of heart rate variability (autonomic balance). The pre-ophthalmic solution administration LF/HF ratio was not significantly different (
P
= 0.59) between the two groups, however, the standard deviation of the LF/HF ratio (LF/HF-SD) tended to be higher in the DE group than that in the non-DE group (
P
= 0.086). The DE symptom intensity was significantly related to LF/HF-SD (
P
= 0.005), which significantly decreased after ophthalmic solution administration in the DE group (
P
= 0.04). The large fluctuations in autonomic balance may be key for the understanding of the mechanism underlying DE symptoms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To estimate the prevalence and risk factors of dry eye disease (DED) in a rural setting in Japan.
Cross-sectional study.
We included 3294 subjects, aged ≥ 40 years who were in the residential ...registry for Koumi town.
Subjects in a rural mountain area, Koumi town, completed questionnaires designed to detect dry eye diagnosis and risk factors.
Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by ophthalmologists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, gender, educational history, smoking history, alcohol drinking history, height and weight, visual display terminal (VDT) use, and contact lens (CL) wear, and past/current history of certain common systemic diseases were the main outcome measures. We used logistic regression analysis to examine associations between DED and other demographic factors.
Of the 3294 eligible residents, 2791 residents (85%) completed the questionnaire. The percentage of women with a composite outcome of clinically diagnosed DED or severe symptoms (21.6%; 95% confidence interval CI, 19.5-23.9) was higher than that of men (12.5%; 95% CI, 10.7-14.5; P<0.001). A low body mass index (BMI; odds ratio OR, 2.07; 95% CI, 0.98-4.39), CL use (OR, 3.84; 95% CI, 1.46-10.10), and hypertension (HT) (OR, 1.39; 95% CI, 0.94-2.06) were risk factors for DED in men. Use of a VDT (OR, 2.33; 95% CI, 1.12-4.85), CL use (OR, 3.61; 95% CI, 2.13-6.10), and myocardial infarction or angina were the risk factors (OR, 2.64; 95% CI, 1.51-4.62), whereas high BMI was a preventive factor (OR, 0.69; 95% CI, 0.48-1.01) for DED in women.
Among a Japanese cohort, DED leading to a clinical diagnosis or severe symptoms is prevalent. Use of CLs was a common dry eye risk factor in both genders. The condition is more prevalent in men with low BMI, HT, and in women with myocardial infarction or angina and VDT use. Relevant measures directed against the modifiable risks may provide a positive impact on public health and quality of life of Japanese.
The authors have no proprietary or commercial interest in any materials discussed in this article.
To describe the clinical and molecular characteristics of patients with childhood-onset Stargardt disease (STGD).
Retrospective case series.
Forty-two patients who were diagnosed with STGD in ...childhood at a single institution between January 2001 and January 2012.
A detailed history and a comprehensive ophthalmic examination were undertaken, including color fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), and pattern and full-field electroretinograms. The entire coding region and splice sites of ABCA4 were screened using a next-generation, sequencing-based strategy. The molecular genetic findings of childhood-onset STGD patients were compared with those of adult-onset patients.
Clinical, imaging, electrophysiologic, and molecular genetic findings.
The median ages of onset and the median age at baseline examination were 8.5 (range, 3–16) and 12.0 years (range, 7-16), respectively. The median baseline logarithm of the minimum angle of resolution visual acuity was 0.74. At baseline, 26 of 39 patients (67%) with available photographs had macular atrophy with macular/peripheral flecks; 11 (28%) had macular atrophy without flecks; 1 (2.5%) had numerous flecks without macular atrophy; and 1 (2.5%) had a normal fundus appearance. Flecks were not identified at baseline in 12 patients (31%). SD-OCT detected foveal outer retinal disruption in all 21 patients with available images. Electrophysiologic assessment demonstrated retinal dysfunction confined to the macula in 9 patients (36%), macular and generalized cone dysfunction in 1 subject (4%), and macular and generalized cone and rod dysfunction in 15 individuals (60%). At least 1 disease-causing ABCA4 variant was identified in 38 patients (90%), including 13 novel variants; ≥2 variants were identified in 34 patients (81%). Patients with childhood-onset STGD more frequently harbored 2 deleterious variants (18% vs 5%) compared with patients with adult-onset STGD.
Childhood-onset STGD is associated with severe visual loss, early morphologic changes, and often generalized retinal dysfunction, despite often having less severe fundus abnormalities on examination. One third of children do not have flecks at presentation. The relatively high proportion of deleterious ABCA4 variants supports the hypothesis that earlier onset disease is often owing to more severe variants in ABCA4 than those found in adult-onset disease.
Defining Dry Eye from a Clinical Perspective Tsubota, Kazuo; Pflugfelder, Stephen C; Liu, Zuguo ...
International journal of molecular sciences,
12/2020, Letnik:
21, Številka:
23
Journal Article
Recenzirano
Odprti dostop
Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the ...involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: "Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities." The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.
Despite the global pandemic of myopia, the precise molecular mechanism of the onset of myopia remains largely unknown. This is partially because of the lack of efficient murine myopic models that ...allow genetic manipulation at low cost. Here we report a highly practical and reproducible lens-induced myopia model by specially designed frames and lenses for mice. A lens power dependent myopic induction in mice was shown until minus 30 diopter lenses. The phenotype was significantly stronger than form-deprivation myopia. We presented the protocol for precise evaluations of the state of myopia, including refraction, corneal curvature and axial length using up-to-date devices. We also found that myopic mouse eyes showed decreased visual acuity on optokinetic response examination. Finally, we confirmed the anti-myopic effect of 1% atropine using this model, which showed its potential in drug screening. The strong phenotype, stable evaluation and the potential for gene manipulation utilizing the presented method in mice will accelerate the translational research of myopia.
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