Amelioration of oxygen-induced retinopathy in neonatal mice with fetal growth restriction.

Introduction: With the aim of optimizing the balance of maintaining a safe oxygen saturation and reducing the risk of retinopathy of prematurity in human neonates with fetal growth restriction (FGR), the present study investigated the distinct effects of oxygen supplementation on the retinal neovasculature using a murine premature neonatal oxygen-induced retinopathy (OIR) model with or without fetal growth restriction. Methods: For comparison with normal birth-weight neonates, maternal low-protein diet-induced FGR neonates were subjected to fluctuating oxygen levels to generate oxygen-induced retinopathy. The retinal neovasculature was histologically evaluated, and comprehensive transcriptome analysis was conducted. Results: Compared to OIR neonates with normal birth weight, significant amelioration of the neovasculature, as indicated by decreases in the number of branch junctions, vascular distribution, maximal vascular radius and microaneurysm-like tufts, was observed in OIR mice with FGR. The results of retinal RNA-sequencing revealed downregulation of angiogenic factors that trigger pathological retinal neovascularization, such as the mitogen-activated protein kinase pathway and corresponding upstream signaling pathways in OIR mice with FGR. Conclusion: Our findings demonstrated that FGR neonates have a higher capacity for retinal oxygen stress, and the risk of OIR development is attenuated compared to that in mature neonates with normal birth weight.

Hypertension facilitates age-related diseases. ~ Is hypertension associated with a wide variety of diseases?~.

Hypertension, a disease whose prevalence increases with age, induces pathological conditions of ischemic vascular disorders such as cerebral infarction and myocardial infarction due to accelerated arteriosclerosis and circulatory insufficiency of small arteries and sometimes causes hemorrhagic conditions such as cerebral hemorrhage and ruptured aortic aneurysm. On the other hand, as it is said that aging starts with the blood vessels, impaired blood flow associated with vascular aging is the basis for the development of many pathological conditions, and ischemic changes in target organs associated with vascular disorders result in tissue dysfunction and degeneration, inducing organ hypofunction and dysfunction. Therefore, we hypothesized that hypertension is associated with all age-related vascular diseases, and attempted to review the relationship between hypertension and diseases for which a relationship has not been previously well reported. Following our review, we hope that a collaborative effort to unravel age-related diseases from the perspective of hypertension will be undertaken together with experts in various specialties regarding the relationship of hypertension to all pathological conditions.

Perspectives on frailty as a total life-course disease with consideration of the fetal environment.

Frailty attracts research as it represents a significant target for intervention to extend the healthy life span. An unanswered question in this field is the time point during the life-course at which an individual becomes predisposed to frailty. Here, we propose that frailty has a fetal origin and should be regarded as part of the spectrum of the developmental origins of health and disease. The developmental origins of health and disease theory originated from findings linking the fetal environment to lifestyle-related disorders such as hypertension and diabetes. Coincidentally, a recent trend in frailty research also centers on vascular dysfunction and metabolic alterations as the causality of lifestyle-related disorders such as sarcopenia and dementia. Here, we explore the relationship between fetal programming, frailty-related disorders (sarcopenia and dementia), and other age-related diseases mainly based on reports on intrauterine growth restriction. We propose a "total" life-course approach to combat frailty. With this viewpoint, not only physicians and gerontologists but also obstetricians and pediatricians should team up to overcome age-related diseases in the elderly. Geriatr Gerontol Int 2023; 23: 263-269.

In Vivo Confocal Microscopic Observations of Vortex Keratopathy in Patients with Amiodarone-Induced Keratopathy and Fabry Disease.

PURPOSE: To compare the morphology of two types of vortex keratopathy: amiodarone-induced keratopathy and the Fabry disease-associated keratopathy. PATIENTS AND METHODS: Eight patients who were receiving oral amiodarone therapy and 3 patients with Fabry disease, a mother and her 2 daughters, were examined by slit-lamp biomicroscopy and in vivo confocal microscopy (IVCM) regularly. RESULTS: Amiodarone-induced keratopathy developed in 7 of the 8 patients, and it was detected as early as 7 days by IVCM and 14 days by slit-lamp biomicroscopy. The in vivo confocal microscopic images showed a clustering of corneal epithelial cells with a highly reflective cytoplasm in both types of keratopathy. In the amiodarone-induced keratopathy, the highly reflective epithelial cells were first found at the center of the cornea and then spread to the periphery with increasing time on amiodarone. In Fabry disease, the highly reflective epithelial cells were consistently observed extending from the limbus to the central cornea. CONCLUSION: These findings suggest that the corneal epithelial cells most likely endocytose amiodarone from the tear film in the amiodarone-induced keratopathy. In Fabry disease, globotriaosylceramide deposits are taken up by the lysosomes of the limbal epithelial stem cells, and they differentiate and migrate to the center of the cornea to form the whorl pattern.