Hyperglycemia-regulated tRNA-derived fragment tRF-3001a propels neurovascular dysfunction in diabetic mice.

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.

Regulatory effect of long-stranded non-coding RNA-CRNDE on neurodegeneration during retinal ischemia-reperfusion.

Ischemia/reperfusion (I/R) injury is a common pathological mechanism involved in many ocular diseases. I/R is characterized by microvascular dysfunction and neurodegeneration. However, the mechanisms of neurodegeneration induced by I/R remain largely unknown. This study showed that the expression of long non-coding RNA-CRNDE was significantly upregulated after retinal ischemia-reperfusion (RIR). LncRNA-CRNDE knockdown alleviated retinal neurodegeneration induced by RIR injury, as shown by decreased reactive gliosis and reduced retinal cells loss. Furthermore, lncRNA-CRNDE knockdown directly regulated Müller cell function and indirectly affected RGC function in vitro. In addition, lncRNA-CRNDE knockdown led to a significant reduction in the release of several cytokines after RIR. This study suggests that lncRNA-CRNDE is a promising therapeutic target for RIR.

Involvement of transient receptor potential channels in ocular diseases: a narrative review.

Background and Objective: Transient receptor potential (TRP) channels are a superfamily of functionally diverse and widely expressed cation channels which exhibit complex regulatory patterns and sensitivity to multiple environmental factors. The involvement of these ion channels is critical in various physiological functions and pathophysiological conditions. In recent decades, a growing number of studies have identified the essential role that TRP channels play in many ocular diseases. In this study, we performed a narrative review of research on the expression and function of TRP channels in various eye diseases. Methods: PubMed, Google Scholar, and Web of Science were searched for all relevant original papers and reviews published from database inception to January 31, 2022. Searches were conducted using the related keywords 'transient receptor potential channels', 'TRPs', 'Ca2+ signaling', 'iron channel', 'TRPV4', 'TRPM1', 'retina', 'optic nerve', 'cornea', 'retinal ganglion cells', 'ON-bipolar', 'TRPs and retina', 'TRP channel and retinal ganglion cells', 'TRPs and cornea', 'diabetes', 'glaucoma', 'dry eye disease', 'cataract', 'retinopathy of prematurity', 'retinoblastoma', and 'congenital stationary night blindness'. Key Content and Findings: In this narrative review, we summarize the history of TRP channels and introduce the TRP channel-related literature in eye disease. Next, we discuss the molecular mechanisms of TRP channels in various eye diseases and suggest future research directions. Conclusions: The relevant studies indicate that TRP channels play vital roles in various eye diseases. However, considerable work is needed to more fully understand the functional and mechanistic aspects of how TRP channels contribute to the pathophysiology of eye disease, especially in the context of animal models and patients. Further investigations will aid in the development of future drugs targeting TRP channels for eye diseases.

Suppression of choroidal neovascularization by silencing of long non-coding RNA IPW.

Long noncoding RNAs (lncRNAs) have emerged as the key regulators in the pathogenesis of human disorders. This study aimed to investigate the role of lncRNA-IPW in the progression of choroidal neovascularization (CNV) and the underlying molecular mechanism. IPW was significantly up-regulated in the choroidal tissues of laser-induced CNV mice and in the endothelial cells in response to hypoxic stress. IPW silencing led to reduced formation of CNV in laser-induced CNV model and ex vivo choroidal sprouting model, which could achieve similar therapeutic effects of anti-VEGF on CNV formation. Silencing or transgenic overexpression of IPW could alter endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, IPW silencing led to increased expression of miR-370. Increased miR-370 could mimic the effects of IPW silencing on CNV formation and endothelial angiogenic phenotypes in vivo and in vitro. This study suggests that IPW silencing is a promising strategy for the treatment of neovascular ocular diseases.