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Polypoidal Choroidal Vasculopathy
Published in Ching-Yu Cheng, Tien Yin Wong, Ophthalmic Epidemiology, 2022
Genetic studies also have tried to identify prognostic factors. So far, most studies have employed a small-scale candidate gene approach. Such studies demonstrated that SNPs in the ARMS2 locus, among other SNPs, may be an important risk factor for severe phenotype. For example, the ARMS2 locus was associated with larger lesion size, higher likelihood of vitreous hemorrhage, and worse visual outcome 1 year after treatment with PDT or combination therapy in PCV.65 It also confers a higher risk for second-eye involvement.66 A prospective multicenter genome-wide association study (GWAS) including 461 treatment-naive exudative AMD patients failed to identify genetic loci associated with treatment outcomes but confirmed that ARMS2/HTRA1 polymorphism might be able to predict the frequency of injection after initial ranibizumab treatment.67 Another GWAS study including 919 exudative AMD patients also failed to identify genetic loci associated with treatment outcomes, but found that four variants showed a suggestive level of associations with visual loss, among which three were VEGF-related pathway (KCNMA1, SOCS2, and OTX2).68
Ependymoma in Childhood and Adolescence
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
A more recent evaluation of the posterior fossa group involving international collaboration on 675 samples has revealed molecular heterogeneity within this group, with nine distinct molecular groups being identified, all with varying prognostic implications. The two most common entities, denoted PFA-1 and PFA-2, have similar outcomes, but distinct histogenesis. PFA-1c was enriched for 1q gain and had a poor prognosis. A better prognostic group was identified characterized by high levels of OTX2 expression. This study also identified a potential role for CXorf67 mutations in the pathogenesis of ependymoma. This important study now needs to be replicated in clinical trial cohorts.81
Regulation of the Pituitary Gland by Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
The ontogeny of the anterior pituitary depends upon a progressive cascade of activated extrinsic or intrinsic transcription factors and signaling molecules. The initial extrinsic phase of murine pituitary development comprises signals emanating from both the ventral diencephalon and the oral ectoderm. As illustrated in Figure 5.8A at mouse embryonic day (E) 6.5–7, the anterior portion of the neural plate is destined to give rise to the primordial pituitary, while the adjacent midline region will become the endocrine hypothalamus [43]. At E8, the oral ectoderm starts to proliferate in response to Shh, Six3, Otx2 and Hex1 and participates in midline formation. Proliferation continues at E9 in response to Bmp4, Fgf8, Wnt2 and Nkx2 coming from the neural epithelium. At the same time, the oral ectoderm begins to invaginate upward and to form a rudimental Rathke’s pouch, which expresses Lhx3/4 and Pitx1/2. At the edge of the pouch, Bmp2 makes contact with the oral ectoderm and antagonizes Fgf2, which is expressed by the neural epithelium. Subsequently, an Bmp2–Fgf8 ventral–dorsal gradient is established that determines the activation of specific genes in each cell group according to their localization within the pouch.
The relevance of the cytogenetic analysis in syndromic microphthalmia/anophthalmia
Published in Ophthalmic Genetics, 2019
David Apam-Garduño, Vianney Cortés-González, Luis Quintana-Fernández, Daniel Martínez-Anaya, Patricia Pérez-Vera, Cristina Villanueva-Mendoza
OTX2-encoded protein acts as a transcription factor and plays a role in brain, craniofacial and sensory organ development. The phenotype of patients with microdeletions encompassing OTX2 includes M/A spectrum, brain malformations, deafness, anomalies of the extremities, cardiac malformations and urogenital abnormalities (OMIM: 610125) (2,8). The brain malformations described are hypoplasia or the absence of optic nerves and optic chiasm, pituitary abnormalities, ventricular dilatation, partial corpus callosum agenesis and reduced hemispheric white matter (8). Other features observed less frequently are hippocampal abnormal gyration, cerebellar hypoplasia and Chiari malformation (8,9). As far as we know, this is the first patient with perisylvian polymicrogyria; this cerebral dysgenesis is characterized by excessive cortical folds and shallow grooves. Perisylvian polymicrogyria manifests with epilepsy, variable developmental delay with language and food learning difficulties (19). This brain condition explains the neurologic status of the patient.
Silver nanoparticles inhibit neural induction in human induced pluripotent stem cells
Published in Nanotoxicology, 2018
Shigeru Yamada, Daiju Yamazaki, Yasunari Kanda
A previous report indicates that ERK signaling inhibits neural induction via OTX2 silencing in human embryonic stem cells (Greber et al. 2011). ERK has been reported to be activated following Mfn1 depletion (Son et al. 2015). Thus, we focused on ERK signaling to understand the effects of AgNPs on neural induction. It was observed that AgNPs significantly increased the basal ERK phosphorylation levels, which were abolished by treatment with the ERK inhibitor U0126 (Figure 4(A,B)). To further understand whether OTX2 downregulation in AgNP-treated cells occurred via ERK signaling, the effect of U0126 on OTX2 expression was examined. Incubation with U0126 recovered the expression levels of OTX2 (Figure 4(C)). These data suggest that AgNPs activate ERK and prevents neural induction via OTX2 downregulation.
Proliferative Cells Isolated from the Adult Human Peripheral Retina only Transiently Upregulate Key Retinal Markers upon Induced Differentiation
Published in Current Eye Research, 2018
Erik O. Johnsen, Rebecca C. Frøen, Ole Kristoffer Olstad, Bjørn Nicolaissen, Goran Petrovski, Morten C. Moe, Agate Noer
23 of the 231 significantly regulated transcripts annotated in the IPA have previously been shown to be involved in eye development. The eye-field transcription factors (EFTFs) together with Otx2 are required and, in some instances, sufficient for proper eye development in vertebrates. 47 In addition to being essential for RPC proliferation, these factors are also involved in the differentiation of various retinal cell types. OTX2 is involved in bipolar, photoreceptor and RPE development 48–51, while PAX6 and SIX3 induce amacrine development. 52PLXNA4 has been shown to be involved in inner retinal stratification and amacrine development/morphology 53, while NTRK2 and MERTK are expressed by RPE cells. Knocking-out (KO) these genes leads to altered and delayed photoreceptor development, or photoreceptor degeneration, respectively. 54–57 All of the genes mentioned above were significantly upregulated after 7 days of differentiation.