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miRNAs, piRNAs, and lncRNAs: A triad of non-coding RNAs regulating the neurovascular unit in diabetic retinopathy and their therapeutic potentials.
Exp Eye Res
January 2025
Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, 605 014, India. Electronic address:
Diabetic Retinopathy (DR), a leading complication of diabetes mellitus, has long been considered as a microvascular disease of the retina. However, recent evidence suggests that DR is a neurovascular disease, characterized by the degeneration of retinal neural tissue and microvascular abnormalities encompassing ischemia, neovascularization, and blood-retinal barrier breakdown, ultimately leading to blindness. The intricate relationship between the retina and vascular cells constitutes a neurovascular unit, a multi-cellular framework of retinal neurons, glial cells, immune cells, and vascular cells, which facilitates neurovascular coupling, linking neuronal activity to blood flow.
View Article and Find Full Text PDFDiabetes Renders Photoreceptors Susceptible to Retinal Ischemia-Reperfusion Injury.
Invest Ophthalmol Vis Sci
November 2024
Department of Ophthalmology and Visual Sciences, University of Michigan, Michigan Medicine, Kellogg Eye Center, Ann Arbor, Michigan, United States.
Purpose: Studies have suggested that photoreceptors (PR) are altered by diabetes, contributing to diabetic retinopathy (DR) pathology. Here, we explored the effect of diabetes on retinal ischemic injury.
Methods: Retinal ischemia-reperfusion (IR) injury was caused by elevation of intraocular pressure in 10-week-old BKS db/db type 2 diabetes mellitus (T2DM) mice or C57BL/6J mice at 4 or 12 weeks after streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM), and respective nondiabetic controls.
Indoxyl sulfate induces retinal microvascular injury via COX-2/PGE activation in diabetic retinopathy.
J Transl Med
September 2024
Department of Ophthalmology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China.
Background: Diabetic retinopathy (DR), the principal cause of acquired blindness among the working-age population, is the most frequent microvascular complication of diabetes. Although metabolic disorders are hypothesized to play a role in its pathogenesis, the underlying mechanism remains largely elusive.
Methods: To elucidate the mechanism, we initially compared metabolite profiles of vitreous fluid between 23 patients with DR and 12 non-diabetic controls using liquid chromatography/tandem mass spectrometry, identifying the distinct metabolite indoxyl sulfate (IS).
Neurovascular dysfunction in psychiatric disorders: Underlying mechanisms and therapeutic approaches.
Eur J Clin Invest
January 2025
University of Coimbra, Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, Coimbra, Portugal.
Background: Neurovascular interfaces, specifically the blood-brain barrier (BBB) and blood-retinal barrier (BRB), play pivotal roles in maintaining the homeostasis of the central nervous system (CNS). For a long time, these structures were seen only as a way of protection, but we currently know that they have a critical role in CNS (dys)function. Several studies have identified neurovascular alterations in early stages of brain and eye diseases, contributing to the pathophysiology of such conditions.
View Article and Find Full Text PDFTissue Inhibitor of Metalloproteinase 3 (TIMP3) mutations increase glycolytic activity and dysregulate glutamine metabolism in RPE cells.
Mol Metab
October 2024
Cole Eye Institute, Department of Ophthalmic Research, Cleveland Clinic Foundation, Cleveland, OH, USA; Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Dept. of Ophthalmology, Cleveland, OH, USA. Electronic address:
Objectives: Mutations in Tissue Inhibitor of Metalloproteinases 3 (TIMP3) cause Sorsby's Fundus Dystrophy (SFD), a dominantly inherited, rare form of macular degeneration that results in vision loss. TIMP3 is synthesized primarily by retinal pigment epithelial (RPE) cells, which constitute the outer blood-retinal barrier. One major function of RPE is the synthesis and transport of vital nutrients, such as glucose, to the retina.
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