ArticleFluids and barriers of the CNS2023
Reduced folate carrier 1 is present in retinal microvessels and crucial for the inner blood retinal barrier integrity.
Article in Fluids and barriers of the CNS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 13 citations in OpenAlex.
- Review
- In search of a mouse model of Spaceflight Associated Neuro-ocular Syndrome using one-carbon genetics.Scientific reports · 2026Article
- Peri-Microvascular Glycogen and Lactate Regulate Capillary Constrictions and Ischemia Outcome in Mice.Journal of neurochemistry · 2026Article
- PDZK1 Protects Against RPE Senescence by Targeting the 14-3-3ε-mTOR Axis to Attenuate Early Diabetic Retinopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Preserving blood-retinal barrier integrity: a path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy.Cell regeneration (London, England) · 2025Review
- Regulation of folate transport at the mouse arachnoid barrier.Fluids and barriers of the CNS · 2024Article
- Pericytes: jack-of-all-trades in cancer-related inflammation.Frontiers in pharmacology · 2024Review
- Case series of retinal vein occlusions showing early recovery using oral l-methylfolate.Therapeutic advances in ophthalmologyArticle
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundReduced folate carrier 1 (RFC1; SLC19a1) is the main responsible transporter for the B9 family of vitamins named folates, which are essential for normal tissue growth and development. While folate deficiency resulted in retinal vasculopathy, the expression and the role of RFC1 in blood-retinal barrier (BRB) are not well known.
methodsWe used whole mount retinas and trypsin digested microvessel samples of adult mice. To knockdown RFC1, we delivered RFC1-targeted short interfering RNA (RFC1-siRNA) intravitreally; while, to upregulate RFC1 we delivered lentiviral vector overexpressing RFC1. Retinal ischemia was induced 1-h by applying FeCl
resultsOur analyses on whole mount retinas and trypsin digested microvessel samples of adult mice revealed the presence of RFC1 in the inner BRB and colocalization with endothelial cells and pericytes. Knocking down RFC1 expression via siRNA delivery resulted in the disintegration of tight junction proteins and collagen-4 in twenty-four hours, which was accompanied by significant endogenous IgG extravasation. This indicated the impairment of BRB integrity after an abrupt RFC1 decrease. Furthermore, lentiviral vector-mediated RFC1 overexpression resulted in increased tight junction proteins and collagen-4, confirming the structural role of RFC1 in the inner BRB. Acute retinal ischemia decreased collagen-4 and occludin levels and led to an increase in RFC1. Besides, the pre-ischemic overexpression of RFC1 partially rescued collagen-4 and occludin levels which would be decreased after ischemia.
conclusionIn conclusion, our study clarifies the presence of RFC1 protein in the inner BRB, which has recently been defined as hypoxia-immune-related gene in other tissues and offers a novel perspective of retinal RFC1. Hence, other than being a folate carrier, RFC1 is an acute regulator of the inner BRB in healthy and ischemic retinas.
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