Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice

Abstract

Statistical analysis was performed with Microsoft Excel, version 16.0.16327.20248, or Prism, version 8.0, software (GraphPad). Statistical differences between 2 or multiple heterogenous groups were determined by unpaired Student's t test or 1-way or 2-way ANOVA. Analysis of data was performed using Excel.Study approval. All animal experiments were performed in accordance with the Animal Care and Use Program at Johns Hopkins University and were approved by the Institutional Animal Care and Use Committee (IACUC). All studies involving patients or patient tissue were approved by the Institutional Review Board of Johns Hopkins University School of Medicine. All participants provided written informed consent prior to enrolment in the study.

Inhibition of hypoxia-inducible factors suppresses subretinal fibrosis

“…Digoxin, another HIF-1 inhibitor, inhibited retinal ischemia-induced HIF-1α expression and further suppressed ocular neovascularization (37). A recently developed HIF inhibitor 32-134D (structurally different from acriflavine) was suggested to inhibit the accumulation of HIFs and normalize HIF-target gene expressions in mice and human retinal organoids (38). The accumulation of HIF-1α in response to transient hypoglycemia has also been suggested to worsen ocular conditions in diabetes (39).…”

Exercise Alleviates Aging of Adipose Tissue through Adipokine Regulation

“…With aging and obesity, the reduced availability of oxygen can trigger cellular hypoxia and inflammation, contributing to local and systemic metabolic dysfunction. Hypoxia-inducible factors (HIFs) play a role in various cellular functions, including glucose utilization, angiogenesis, apoptosis, extracellular matrix (ECM) remodeling, recruitment of macrophages, and fibrosis [ 29 , 30 ]. The hypertrophic growth associated with aging results in reduced oxygen diffusion, exacerbated by insufficient compensation from the vasculature.…”