Correlation between optic nerve head circulation and visual function before and after anti-VEGF therapy for central retinal vein occlusion : prospective, interventional case series

Background: To determine the correlation between the optic nerve head (ONH) circulation determined by laser speckle flowgraphy and the best-corrected visual acuity or retinal sensitivity before and after intravitreal bevacizumab or ranibizumab for central retinal vein occlusion. Methods: Thirty-one eyes of 31 patients were treated with intravitreal bevacizumab or ranibizumab for macular edema due to a central retinal vein occlusion. The blood flow in the large vessels on the ONH, the best-corrected visual acuity, and retinal sensitivity were measured at the baseline, and at 1, 3, and 6 months after treatment. The arteriovenous passage time on fluorescein angiography was determined. The venous tortuosity index was calculated on color fundus photograph by dividing the length of the tortuous retinal vein by the chord length of the same segment. The blood flow was represented by the mean blur rate (MBR) determined by laser speckle flowgraphy. To exclude the influence of systemic circulation and blood flow in the ONH tissue, the corrected MBR was calculated as MBR of ONH vessel area – MBR of ONH tissue area in the affected eye divided by the vascular MBR – tissue MBR in the unaffected eye. Pearson’s correlation tests were used to determine the significance of correlations between the MBR and the best-corrected visual acuity, retinal sensitivity, arteriovenous passage time, or venous tortuosity index. Results: At the baseline, the corrected MBR was significantly correlated with the arteriovenous passage time and venous tortuosity index (r = -0.807, P < 0.001; r = -0.716, P < 0.001; respectively). The corrected MBR was significantly correlated with the best-corrected visual acuity and retinal sensitivity at the baseline, and at 1, 3, and 6 months (all P < 0.050). The corrected MBR at the baseline was significantly correlated with the best-corrected visual acuity at 6 months (r = -0.651, P < 0.001) and retinal sensitivity at 6 months (r = 0.485, P = 0.005). Conclusions: The pre-treatment blood flow velocity of ONH can be used as a predictive factor for the best-corrected visual acuity and retinal sensitivity after anti-VEGF therapy for central retinal vein occlusion. Trial registration: Trial Registration number: UMIN000009072. Date of registration: 10/15/2012

Osteoclasts adapt to physioxia perturbation through DNA demethylation

Oxygen plays an important role in diverse biological processes. However, since quantitation of the partial pressure of cellular oxygen in vivo is challenging, the extent of oxygen perturbation in situ and its cellular response remains underexplored. Using two-photon phosphorescence lifetime imaging microscopy, we determine the physiological range of oxygen tension in osteoclasts of live mice. We find that oxygen tension ranges from 17.4 to 36.4 mmHg, under hypoxic and normoxic conditions, respectively. Physiological normoxia thus corresponds to 5% and hypoxia to 2% oxygen in osteoclasts. Hypoxia in this range severely limits osteoclastogenesis, independent of energy metabolism and hypoxia-inducible factor activity. We observe that hypoxia decreases ten-eleven translocation (TET) activity. Tet2/3 cooperatively induces Prdm1 expression via oxygen-dependent DNA demethylation, which in turn activates NFATc1 required for osteoclastogenesis. Taken together, our results reveal that TET enzymes, acting as functional oxygen sensors, regulate osteoclastogenesis within the physiological range of oxygen tension, thus opening new avenues for research on in vivo response to oxygen perturbation.Nishikawa K., Seno S., Yoshihara T., et al. Osteoclasts adapt to physioxia perturbation through DNA demethylation. EMBO Reports 22, e53035 (2021); https://doi.org/10.15252/embr.202153035

Remarkable changes in behavior and physiology of laboratory mice after the massive 2011 Tohoku earthquake in Japan.

A devastating earthquake and tsunami hit Japan on March 11, 2011, followed by several long and intense aftershocks. Laboratory mice housed in the Tokyo, located approximately 330 km south of this earthquake's epicenter, displayed remarkable changes in a variety of behaviors and physiological measures. Although unusual pre-earthquake behaviors have been previously reported in laboratory animals, little is known about behavioral and physiological changes that occur after a great earthquake. In the present study, the effects of Tohoku earthquake on mice behavior were investigated. "Earthquake-experienced" mice displayed a marked increase in food consumption without gaining body weight in response to the earthquake. They also displayed enhanced anxiety, and in a formal fear memory task, showed significantly greater tone- and context-dependent conditioned freezing. Water maze performance of earthquake-experienced mice showed the quicker acquisition of the task, faster swim speed and longer swim distance than the naive mice. Serum corticosterone levels were elevated compared to the naive mice, indicating that the earthquake and aftershocks were stressful for the mice. These results demonstrate that great earthquakes strongly affect mouse behaviors and physiology. Although the effects of a variety of experimental manipulations on mouse behaviors in disease models or in models of higher cognitive functions have been extensively examined, researchers need to be aware how natural phenomena, such as earthquakes and perhaps other natural environmental factors, influence laboratory animal behaviors and physiology

Swept-Source Optical Coherence Tomographic Findings of Choroidal Osteoma

Purpose: To report the morphologic features of a choroidal osteoma using swept-source optical coherence tomography (SS-OCT) and fundus autofluorescence (FAF). Methods: Two eyes of two cases with a choroidal osteoma were studied using SS-OCT and FAF. Results: The location of the tumor was circumpapillary without macular involvement in case 1 and juxtapapillary with macular involvement in case 2. Both cases had a mixture of calcified and decalcified areas, and a concomitant choroidal neovascularization was found in case 2. The FAF images showed decreased autofluorescence in the central decalcified regions and relatively preserved fluorescence in marginal calcified regions in both cases. SS-OCT revealed a normal inner retina and an abnormal outer retina in both cases, and subretinal fluid in case 2. The calcified regions appeared sponge-like and were multilayered in case 2. A lamellar reflective pattern was observed in the decalcified regions in case 1, and hyperreflective mound-like areas were observed in both cases. SS-OCT demonstrated hyperreflective areas above Bruch's membrane accompanied by disruption of Bruch's membrane in case 1. The chorioscleral border was visible in both cases. Conclusions: The FAF pattern in the calcified and decalcified areas of the choroidal osteoma may correspond to the different stage of tumor evolution. The SS-OCT findings indicate that choroidal osteomas can have characteristic reflective patterns and alterations of the overlying retina

Number of earthquake and its intensity observed in the Tokyo area during the testing period for naive mice. ^*

*<p>The data relating to the earthquake were obtained from Japan Meteorological Agency. The earthquake greater than intensity scale 2–3 was not observed in this period.</p

Pavlovian fear conditioning using a weak training protocol.

<p>After conditioning, conditioned freezing to tone and context was sequentially measured in earthquake-experienced (n = 10), naive (n = 7), and non-conditioned naive mice (n = 6). (A) Tone-dependent short-term memory test was carried out 1 h after the conditioning. No differences were found among the three groups of mice before the presentation of the tone. However, the earthquake-experienced mice exhibited significantly higher freezing than non-conditioned naive mice during tone presentation. (B) Tone-dependent long-term memory examined 24 h after the conditioning. Conditioned freezing of earthquake-experienced mice was significantly higher than that of the other two groups of naive mice before and during the tone. (C) Context-dependent long-term memory examined 48 h after the conditioning. Conditioned freezing to context was higher in earthquake-experienced mice than in the other two groups of naive mice. †<i>p</i><0.10, *<i>p</i><0.05, **<i>p</i><0.01 compared with naive and/or non-conditioned naive mice. Error bars indicate S.E.M.</p

Number of mice food consumption and its body weight.

<p>(A) Mean food consumption of 24 earthquake-experienced mice significantly increased after the main seismic event. Since mice were housed in groups of four per cage, mean food consumption was calculated per cage and was regarded as representative value for four mice housed in one cage. Error bars indicate S.E.M. (B) Mean body weight of earthquake-experienced (n = 24) and age-matched naive mice (n = 24). Black arrows in both figures indicate March 11, 2011, when the main seismic event of the Tohoku earthquake occurred. Note that x-axis represents weeks of age and that the data for age-matched naive mice were obtained before March 11, 2011.</p