-
Cell Reports. Medicine Oct 2023Neurovascular dysfunction is a preclinical manifestation of diabetic complications, including diabetic retinopathy (DR). Herein, we report that a transfer RNA-derived...
Neurovascular dysfunction is a preclinical manifestation of diabetic complications, including diabetic retinopathy (DR). Herein, we report that a transfer RNA-derived RNA fragment, tRF-3001a, is significantly upregulated under diabetic conditions. tRF-3001a downregulation inhibits Müller cell activation, suppresses endothelial angiogenic effects, and protects against high-glucose-induced retinal ganglion cell injury in vitro. Furthermore, tRF-3001a downregulation alleviates retinal vascular dysfunction, inhibits retinal reactive gliosis, facilitates retinal ganglion cell survival, and preserves visual function and visually guided behaviors in STZ-induced diabetic mice and db/db diabetic mice. Mechanistically, tRF-3001a regulates neurovascular dysfunction in a microRNA-like mechanism by targeting GSK3B. Clinically, tRF-3001a is upregulated in aqueous humor (AH) samples of DR patients. tRF-3001a downregulation inhibits DR-induced human retinal vascular endothelial cell and Müller cell dysfunction in vitro and DR-induced retinal neurovascular dysfunction in C57BL/6J mice. Thus, targeting tRF-3001a-mediated signaling is a promising strategy for the concurrent treatment of vasculopathy and neuropathy in diabetes mellitus.
Topics: Mice; Humans; Animals; Diabetes Mellitus, Experimental; Mice, Inbred C57BL; Retina; Diabetic Retinopathy; Hyperglycemia
PubMed: 37757825
DOI: 10.1016/j.xcrm.2023.101209 -
International Journal of Molecular... Jun 2023Elevated levels of homocysteine (Hcy), a non-proteinogenic amino acid, may lead to a host of manifestations across the biological systems, particularly the nervous... (Review)
Review
Elevated levels of homocysteine (Hcy), a non-proteinogenic amino acid, may lead to a host of manifestations across the biological systems, particularly the nervous system. Defects in Hcy metabolism have been associated with many neurodegenerative diseases including glaucoma, i.e., the leading cause of blindness. However, the pathophysiology of elevated Hcy and its eligibility as a risk factor for glaucoma remain unclear. We aimed to provide a comprehensive review of the relationship between elevated Hcy levels and glaucoma. Through a systemic search of the PubMed and Google Scholar databases, we found that elevated Hcy might play an important role in the pathogenesis of glaucoma. Further research will be necessary to help clarify the specific contribution of elevated Hcy in the pathogenesis of glaucoma. A discovery and conceptual understanding of Hcy-associated glaucoma could be the keys to providing better therapeutic treatment, if not prophylactic treatment, for this disease.
Topics: Humans; Glaucoma, Open-Angle; Glaucoma; Amino Acids; Risk Factors; Homocysteine
PubMed: 37445966
DOI: 10.3390/ijms241310790