A Case of Focal Choroidal Excavation Development Associated with Multiple Evanescent White Dot Syndrome

Focal choroidal excavation (FCE) is described as an excavated lesion of the choroid that can be detected by optical coherence tomography (OCT). While the exact pathogenesis of FCE remains unclear, it has been proposed in some cases that there is an association with the inflammation in the outer retina. We present a case of FCE development that was detected by spectral domain OCT (SD-OCT) and found to be associated with multiple evanescent white dot syndrome (MEWDS). A 40-year-old Japanese woman was diagnosed with MEWDS based on multiple white dots observed from the posterior pole to the midperiphery, along with yellow granularity in the fovea. SD-OCT revealed separation between the retinal pigment epithelium (RPE) and Bruch’s membrane (BM) and discontinuations of the ellipsoid zone, RPE, and BM. At 4 weeks after onset, several of the white dots disappeared, the yellow granularity in the fovea became small, and we detected nonconforming choroidal excavation under the central fovea. The choroidal excavation gradually deepened and changed to a conforming pattern. These findings suggest that the degree of the impairment caused by inflammation and the plasticity of the BM and RPE complex may be associated with different types of acquired FCE

The Identification of Zebrafish Mutants Showing Alterations in Senescence-Associated Biomarkers

There is an interesting overlap of function in a wide range of organisms between genes that modulate the stress responses and those that regulate aging phenotypes and, in some cases, lifespan. We have therefore screened mutagenized zebrafish embryos for the altered expression of a stress biomarker, senescence-associated β-galactosidase (SA-β-gal) in our current study. We validated the use of embryonic SA-β-gal production as a screening tool by analyzing a collection of retrovirus-insertional mutants. From a pool of 306 such mutants, we identified 11 candidates that showed higher embryonic SA-β-gal activity, two of which were selected for further study. One of these mutants is null for a homologue of Drosophila spinster, a gene known to regulate lifespan in flies, whereas the other harbors a mutation in a homologue of the human telomeric repeat binding factor 2 (terf2) gene, which plays roles in telomere protection and telomere-length regulation. Although the homozygous spinster and terf2 mutants are embryonic lethal, heterozygous adult fish are viable and show an accelerated appearance of aging symptoms including lipofuscin accumulation, which is another biomarker, and shorter lifespan. We next used the same SA-β-gal assay to screen chemically mutagenized zebrafish, each of which was heterozygous for lesions in multiple genes, under the sensitizing conditions of oxidative stress. We obtained eight additional mutants from this screen that, when bred to homozygosity, showed enhanced SA-β-gal activity even in the absence of stress, and further displayed embryonic neural and muscular degenerative phenotypes. Adult fish that are heterozygous for these mutations also showed the premature expression of aging biomarkers and the accelerated onset of aging phenotypes. Our current strategy of mutant screening for a senescence-associated biomarker in zebrafish embryos may thus prove to be a useful new tool for the genetic dissection of vertebrate stress response and senescence mechanisms

A Non-Canonical Function of Zebrafish Telomerase Reverse Transcriptase Is Required for Developmental Hematopoiesis

Although it is clear that telomerase expression is crucial for the maintenance of telomere homeostasis, there is increasing evidence that the TERT protein can have physiological roles that are independent of this central function. To further examine the role of telomerase during vertebrate development, the zebrafish telomerase reverse transcriptase (zTERT) was functionally characterized. Upon zTERT knockdown, zebrafish embryos show reduced telomerase activity and are viable, but develop pancytopenia resulting from aberrant hematopoiesis. The blood cell counts in TERT-depleted zebrafish embryos are markedly decreased and hematopoietic cell differentiation is impaired, whereas other somatic lineages remain morphologically unaffected. Although both primitive and definitive hematopoiesis is disrupted by zTERT knockdown, the telomere lengths are not significantly altered throughout early development. Induced p53 deficiency, as well as overexpression of the anti-apoptotic proteins Bcl-2 and E1B-19K, significantly relieves the decreased blood cells numbers caused by zTERT knockdown, but not the impaired blood cell differentiation. Surprisingly, only the reverse transcriptase motifs of zTERT are crucial, but the telomerase RNA-binding domain of zTERT is not required, for rescuing complete hematopoiesis. This is therefore the first demonstration of a non-canonical catalytic activity of TERT, which is different from “authentic” telomerase activity, is required for during vertebrate hematopoiesis. On the other hand, zTERT deficiency induced a defect in hematopoiesis through a potent and specific effect on the gene expression of key regulators in the absence of telomere dysfunction. These results suggest that TERT non-canonically functions in hematopoietic cell differentiation and survival in vertebrates, independently of its role in telomere homeostasis. The data also provide insights into a non-canonical pathway by which TERT functions to modulate specification of hematopoietic stem/progenitor cells during vertebrate development. (276 words

Case of Repeated Full-Thickness Macular Hole Formations and Spontaneous Closure following Intravitreal Bevacizumab Treatment for Central Retinal Vein Occlusion

The development of a full-thickness macular hole (FTMH) is a rare complication of intravitreal injections, and only a small subset of eyes with an FTMH has a spontaneous closure. We report a case of repeated FTMH formations and a spontaneous closure following an intravitreal injection of bevacizumab (IVB) for a central retinal vein occlusion (CRVO). A 39-year-old male patient presented with reduced vision in his right eye and was diagnosed with a CRVO. Two months later, neovascular glaucoma and macular edema (ME) developed and IVB was performed. After 2 weeks, optical coherence tomography revealed an improvement of the ME and the formation of an FTMH with a hyperreflective material in the FTMH. Two months later, there was a recurrence of the ME and a closure of the FTMH, but the hyperreflective material was still present in the retina. Then, another IVB and panretinal photocoagulation were performed. One month later, the ME had improved and the FTMH was closed, but the hyperreflective material was still present in the retina. After another 2 months, the ME recurred and a third IVB was performed. The ME improved without a recurrence of an FTMH. After that, there were no recurrences of the ME, but the FTMH recurred with the progression of a posterior vitreous detachment and development of an epiretinal membrane 1 year after the third IVB. We suggest that an FTMH be included as a complication of intravitreal injections, and it may close spontaneously during the course of the primary disease

Association of energy availability with resting metabolic rates in competitive female teenage runners : a cross-sectional study

Background: Resting metabolic rate (RMR) has been examined as a proxy for low energy availability (EA). Previous studies have been limited to adult athletes, despite the serious health consequences of low EA, particularly during adolescence. This study aimed to explore the relationship between RMR and EA in competitive teenage girl runners. Methods: Eighteen girl runners (mean ± standard-deviation; age, 16.8 ± 0.9 years; body mass, 45.6 ± 5.2 kg, %fat, 13.5 ± 4.2 %) in the same competitive high-school team were evaluated. Each runner was asked to report dietary records with photos and training logs for seven days. Energy intake (EI) was assessed by Registered Dietitian Nutritionists. The runners were evaluated on a treadmill with an indirect calorimeter to yield individual prediction equations for oxygen consumption using running velocity and heart rate (HR). Exercise energy expenditure (EEE) was calculated by the equations based on training logs and HR. Daily EA was calculated by subtracting EEE from EI. The daily means of these variables were calculated. RMR was measured early in the morning by whole-room calorimetry after overnight sleep on concluding the final day of the seven-day assessment. The ratio of measured RMR to predicted RMR (RMR ratio) was calculated by race, age, sex-specific formulae, and Cunningham’s equation. Body composition was measured using dual-energy X-ray absorptiometry. Bivariate correlation analyses were used to examine the relationship between variables. Results: RMR, EI, EEE, and EA were 26.9 ± 2.4, 56.8 ± 15.2, 21.7 ± 5.9, and 35.0 ± 15.0 kcal⋅kg−1 FFM⋅d−1, respectively. RMR reduced linearly with statistical significance, while EA decreased to a threshold level (30 kcal⋅kg−1 FFM⋅d−1) (r= 0.58, p= 0.048). Further reduction in RMR was not observed when EA fell below the threshold. There was no significant correlation between RMR ratios and EA, irrespective of the prediction formulae used. Conclusions: These results suggest that RMR does not reduce with a decrease in EA among highly competitive and lean teenage girl runners. RMR remains disproportionally higher than expected in low EA states. Free-living teenage girl runners with low EA should be cautiously identified using RMR as a proxy for EA change