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1.
Migraine is a complex neurological disorder with a significant impact on patients and society. Clinical and preclinical studies have established the neuropeptide calcitonin gene-related peptide (CGRP) as a key player in migraine and other neurovascular headaches. To study the role of CGRP in these disorders, we have characterized the photophobic phenotype of nestin/hRAMP1 mice, a transgenic model with genetically engineered increased sensitivity to CGRP. These mice have increased nervous system expression of a regulatory subunit of the CGRP receptor, human receptor activity-modifying receptor (hRAMP1). We have previously demonstrated that nestin/hRAMP1 mice display a light-aversive behavior that is greatly enhanced by CGRP and blocked by a CGRP receptor antagonist used to treat migraine. Here we have compared their behavior in two different experimental setups with testing chambers of different sizes and light intensities as well as in complete darkness. We demonstrated similar degrees of light aversion in nestin/hRAMP1 mice with 1000 and 50 lux. To control for other possible factors driving nestin/hRAMP1 mice to the dark zone, we tested them in the absence of any light, and they showed identical behavior as littermates. Furthermore, both nestin/hRAMP1 and control mice have decreased motility in response to CGRP in the dark, but not the light side of the chamber. Our findings confirm the robust CGRP-induced light-aversive phenotype of nestin/hRAMP1 mice, which can be a surrogate of photophobia, and validates its usefulness as a model of migraine and other disorders associated with photophobia. 相似文献
2.
Previous evidence suggests optical treatments hold promise for treating migraine and photophobia. We designed an optical notch filter, centered at 480 nm to reduce direct stimulation of intrinsically photosensitive retinal ganglion cells. We used thin-film technology to integrate the filter into spectacle lenses. Our objective was to determine if an optical notch filter, designed to attenuate activity of intrinsically photosensitive retinal ganglion cells, could reduce headache impact in chronic migraine subjects. For this randomized, double-masked study, our primary endpoint was the Headache Impact Test (HIT-6; GlaxoSmithKline, Brentford, Middlesex, UK). We developed two filters: the therapeutic filter blocked visible light at 480 nm; a 620 nm filter was designed as a sham. Participants were asked to wear lenses with one of the filters for 2 weeks; after 2 weeks when no lenses were worn, they wore lenses with the other filter for 2 weeks. Of 48 subjects, 37 completed the study. Wearing either the 480 or 620 nm lenses resulted in clinically and statistically significant HIT-6 reductions. However, there was no significant difference when comparing overall effect of the 480 and 620 nm lenses. Although the 620 nm filter was designed as a sham intervention, research published following the trial indicated that melanopsin, the photopigment in intrinsically photosensitive retinal ganglion cells, is bi-stable. This molecular property may explain the unexpected efficacy of the 620 nm filter. These preliminary findings indicate that lenses outfitted with a thin-film optical notch filter may be useful in treating chronic migraine. 相似文献
3.
《Archivos de la Sociedad Espa?ola de Oftalmología》2021,96(8):446-448
The case concerns a 54-year-old woman, with a history of fibromyalgia and normal preoperative ocular and systemic study, who presented with a long-lasting disabling photophobia, after sequential bilateral cataract surgery without complications. Photophobia was accompanied by good uncorrected VA, with no pain or subjective eye discomfort, without migraine or indicators of psychic conflict. It was refractory to any prescribed treatment of the ocular surface, finally responding to oral anticonvulsants (carbamazepine) that are frequently used in neuropathic pain. To the best of our knowledge this is the first reported case of a long-lasting disabling photophobia without pain and good VA after cataract surgery. 相似文献
4.
Light absorption by macular pigment may attenuate visual discomfort, or photophobia, for targets composed of short-wavelength light. Macular pigment optical density (MPOD) and photophobia light thresholds were measured psychophysically in 10 subjects. The energy necessary to induce photophobia for a short-wavelength target relative to a long-wavelength target was linearly related to MPOD, as well as estimates of peak MPOD and integrated macular pigment. In four subjects who consumed lutein supplements, increases in MPOD corresponded to increases in photophobia light thresholds. Light absorption by macular pigment appears to influence the amount of short-wavelength light necessary to elicit photophobia. 相似文献
5.
J-Y Choi K Oh B-J Kim C-S Chung S-B Koh & K-W Park 《Cephalalgia : an international journal of headache》2009,29(9):953-959
Photophobia is an important criterion for the diagnosis of migraine. However, several Asian epidemiological surveys about migraine have shown lesser prevalence of photophobia than that of Western studies. This discrepancy is probably caused by underestimation of photophobia due to inappropriate questioning of patients by physicians. To investigate this issue, we developed a questionnaire about photophobia and evaluated its usefulness in 103 patients with migraine. In phase 1 of the study, we found good repeatability of the questionnaire with a 0.826 κ coefficient. In phase 2, the prevalence of photophobia from interviews and that from the questionnaire were compared. The prevalence of interview-documented photophobia was 51.5% and of questionnaire-documented photophobia 82.5% ( P < 0.001). In phase 3, we attempted to make a short-form questionnaire with the same detection power of the questionnaire study. Two short-form questionnaires were identified as a useful method for detecting photophobia. The prevalence of photophobia could be underreported via interview, especially in Asian migraineurs. Using this questionnaire to test for photophobia, the diagnostic rate of photophobia and migraine could be improved. 相似文献
6.
Bright light can cause ocular discomfort and/or pain; however, the mechanism linking luminance to trigeminal nerve activity is not known. In this study we identify a novel reflex circuit necessary for bright light to excite nociceptive neurons in superficial laminae of trigeminal subnucleus caudalis (Vc/C1). Vc/C1 neurons encoded light intensity and displayed a long delay (>10 s) for activation. Microinjection of lidocaine into the eye or trigeminal root ganglion (TRG) inhibited light responses completely, whereas topical application onto the ocular surface had no effect. These findings indicated that light-evoked Vc/C1 activity was mediated by an intraocular mechanism and transmission through the TRG. Disrupting local vasomotor activity by intraocular microinjection of the vasoconstrictive agents, norepinephrine or phenylephrine, blocked light-evoked neural activity, whereas ocular surface or intra-TRG microinjection of norepinephrine had no effect. Pupillary muscle activity did not contribute since light-evoked responses were not altered by atropine. Microinjection of lidocaine into the superior salivatory nucleus diminished light-evoked Vc/C1 activity and lacrimation suggesting that increased parasympathetic outflow was critical for light-evoked responses. The reflex circuit also required input through accessory visual pathways since both Vc/C1 activity and lacrimation were prevented by local blockade of the olivary pretectal nucleus. These findings support the hypothesis that bright light activates trigeminal nerve activity through an intraocular mechanism driven by a luminance-responsive circuit and increased parasympathetic outflow to the eye. 相似文献
7.
Jun-Oh Shin Dongyoung Roh Kihyuk Shin Woo-Il Kim Min-Young Yang Won-Ku Lee Hoon-Soo Kim Byung-Soo Kim Moon-Bum Kim Hyun-Chang Ko 《ANNALS OF DERMATOLOGY》2022,34(1):59
Ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome is a rare genetic disorder caused by mutations in the MBTPS2 gene. It is characterized by ichthyosis and alopecia from birth. Photophobia may be present in infancy or early childhood. Its mode of inheritance is X-linked recessive; thus, it mostly affects male. The disease severity varies, ranging from mild cases limited to the skin to the severe variant involving multiple extracutaneous features. A 7-year-old boy presented with scanty hair on scalp and eyebrows at birth. On physical examination, scaly patches were observed on the whole body and spiky follicular hyperkeratotic papules were observed on the face and trunk. He also suffered from severe photophobia. Histopathological examination of the scalp showed miniaturized hair follicles without perifollicular fibrosis. Genetic analysis revealed a novel mutation in the MBTPS2 gene which was a homozygous missense mutation of c.245T>C leading to an amino-acid substitution from phenylalanine to serine (p.Phe82Ser). We diagnosed this patient with IFAP syndrome. To date, 25 pathogenic MBTPS2 gene mutations have been identified. To our knowledge, c.245T>C is a novel homozygous missense mutation in the MBTPS2 gene, which has not been reported in Human Gene Mutation Database, ClinVar Database, and Leiden Open Variation Database. Previous reports suggested genotype-phenotype correlations in the MBTPS2 gene mutations. Supported by a previous notion that genotype correlates with phenotype, this novel mutation can be a predictive factor for the mild form of IFAP syndrome, restricted to the classic symptom triad. 相似文献
8.
Khan NA 《Microbial pathogenesis》2003,34(6):277-285
Acanthamoeba are free-living, harmless organisms, however, given the opportunity and the appropriate conditions, they can cause painful, sight-threatening as well as fatal infections and, thus, are considered opportunistic pathogens. Acanthamoeba infections have become increasingly important in the past few years due to increasing populations of contact lens users and AIDS patients. The mechanisms associated with the pathogenesis of Acanthamoeba tend to be highly complex, depending on parasite, host and the environmental factors. Elucidation of the biochemical, cellular and molecular basis of the pathogenesis of diseases caused by Acanthamoeba may lead to the development of therapeutic interventions. 相似文献
9.
We describe an 18-month-old male infant suffering from the ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome and further delineate the clinical phenotype. Severe retardation of growth and psychomotor development, chill-like seizures, bronchial asthma, urticaria, a proneness to skin infections and transient nail dystrophy observed in our patient are nonobligatory manifestations of this disorder. Histological examination of the atrichia revealed poorly developed, shortened hair follicles and a complete absence of sebaceous glands. The sex ratio of published cases suggests an X-linked recessive inheritance. The marked clinical variability of the IFAP syndrome might be the expression of a contiguous gene defect.Presented in part at the Fifth International Congress of Paediatric Dermatology, Milan/Italy, 11–15 July, 1989 相似文献
10.
目的 报道一个酪氨酸血症Ⅱ型家系,并进行致病基因突变分析。方法 分析1例10岁男性酪氨酸血症Ⅱ型先证者临床资料,收集其家系3代19人的血液、尿液标本,检测血、尿氨基酸含量;提取家系全部成员基因组DNA,检测酪氨酸氨基转移酶(TAT)基因突变。结果 患儿出生2个月后开始出现畏光,其后症状逐渐加重。6岁时,出现眼睛畏光疼痛。8岁时,手指指尖及足底等部位出现线状角化性斑块,触痛明显。眼科检查:角膜染色和眼底未见明显异常。皮肤科检查:双手指、足底多发线状角化性斑块。血液酪氨酸含量825.64 μmol/L,尿液对羟基苯乳酸161.4 μmol/L。TAT基因检测示患儿2号外显子第236位碱基G突变为A,致甘氨酸突变为谷氨酸(c.236G > A,p.Gly79Glu);10号外显子第1141位碱基G突变为T,致谷氨酸突变为终止密码子(c.1141G > T,p.Glu381*)。该家系中仅患儿患病,父系家族中部分成员携带c.1141G > T(p.Glu381*)突变,母系家族中部分成员携带c.236G > A(p.Gly79Glu)突变。结论 在国内首次报道1例氨基酸血症Ⅱ型,在TAT基因上发现2个新的杂合突变,可能是导致该患儿发病的致病突变。 相似文献