Rice Bran and Vitamin B6 Suppress Pathological Neovascularization in a Murine Model of Age-Related Macular Degeneration as Novel HIF Inhibitors

Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age-related macular degeneration (AMD) in the elderly. Inhibiting neovascularization via antivascular endothelial growth factor (VEGF) drugs has been used for the effective treatment. However, anti-VEGF therapies may cause development of chorioretinal atrophy as they affect a physiological amount of VEGF essential for retinal homeostasis. Furthermore, anti-VEGF therapies are still ineffective in some cases, especially in patients with AMD. Hypoxia-inducible factor (HIF) is a strong regulator of VEGF induction under hypoxic and other stress conditions. Our previous reports have indicated that HIF is associated with pathological retinal neovascularization in murine models of ROP and AMD, and HIF inhibition suppresses neovascularization by reducing an abnormal increase in VEGF expression. Along with this, we attempted to find novel effective HIF inhibitors from natural foods of our daily lives. Food ingredients were screened for prospective HIF inhibitors in ocular cell lines of 661W and ARPE-19, and a murine AMD model was utilized for examining suppressive effects of the ingredients on retinal neovascularization. As a result, rice bran and its component, vitamin B6 showed inhibitory effects on HIF activation and suppressed VEGF mRNA induction under a CoCl2-induced pseudo-hypoxic condition. Dietary supplement of these significantly suppressed retinal neovascularization in the AMD model. These data suggest that rice bran could have promising therapeutic values in the management of pathological ocular neovascularization

Deep learning segmentation of non-perfusion area from color fundus images and AI-generated fluorescein angiography

Abstract The non-perfusion area (NPA) of the retina is an important indicator in the visual prognosis of patients with branch retinal vein occlusion (BRVO). However, the current evaluation method of NPA, fluorescein angiography (FA), is invasive and burdensome. In this study, we examined the use of deep learning models for detecting NPA in color fundus images, bypassing the need for FA, and we also investigated the utility of synthetic FA generated from color fundus images. The models were evaluated using the Dice score and Monte Carlo dropout uncertainty. We retrospectively collected 403 sets of color fundus and FA images from 319 BRVO patients. We trained three deep learning models on FA, color fundus images, and synthetic FA. As a result, though the FA model achieved the highest score, the other two models also performed comparably. We found no statistical significance in median Dice scores between the models. However, the color fundus model showed significantly higher uncertainty than the other models (p < 0.05). In conclusion, deep learning models can detect NPAs from color fundus images with reasonable accuracy, though with somewhat less prediction stability. Synthetic FA stabilizes the prediction and reduces misleading uncertainty estimates by enhancing image quality

Therapeutic Effect of Garcinia cambogia Extract and Hydroxycitric Acid Inhibiting Hypoxia-Inducible Factor in a Murine Model of Age-Related Macular Degeneration

Background: Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. Methods: Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. Results: Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model

核家族における乳幼児期の母親の育児不安 : 育児不安に影響する人的環境要因

A市B区における3ヶ月児,1歳6ヶ月児,3歳児の核家族世帯の母親300人を対象に,人的環境面が育児不安にどのように影響しているかについて検討した。母親の育児歴や育児の協力者の有無,児の年齢などにより母親の抱える悩みは様々であった。育児を行うにあたり多少の悩みを持つこと自体は問題ではなく,悩みの程度や育児環境,協力者の有無,協力者の精神的なサポートが得られるかどうかが大切である。それ故,近年の社会情勢を加味し,地域特性を捉えた上で母親だけでなく,父親も含めた妊娠期からの継続した関わりが必要である。そのためには,保健師は子育ての情報や知識の提供だけでなく,育児者間の交流が図れる場や,いつでも悩みを打ち明けられる場の提供などの精神面のフォローが必要である。We investigated the effect of social and home environmental factors upon child care anxiety of 300 mothers who had infants aged 3 months, 1.5 years and 3 years in B region, Osaka. Depending upon the mother\u27s experience of child care, their co-operators, age of infants and their life style, there were various problems in their child care. It is natural for mothers to experience some difficulty in raising their children, but the main focus of this discussion is the degree of these difficulties, child care environment and level of mental support of their co-operators. It is necessary for proper child care for the mother and father to have a continuous relationship from pregnancy while taking into consideration social life and local environment. Therefore, public health nurses must strive to establish a facility where information and knowledge can be exchanged the mother\u27s problems can be discussed, and not simply prepare and dispense the information