ArticleEye (London, England)2014
Ritonavir inhibits HIF-1α-mediated VEGF expression in retinal pigment epithelial cells in vitro.
Article in Eye (London, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 40 citations in OpenAlex.
- Retinal Ischemia: Therapeutic Effects and Mechanisms of Paeoniflorin.International journal of molecular sciences · 2025Article
- Epigallocatechin-3-Gallate, an Active Green Tea Component to Support Anti-VEGFA Therapy in Wet Age-Related Macular Degeneration.Nutrients · 2023Review
- Assessing the protective effects of cryptotanshinone on CoClMolecular medicine reports · 2021Article
- Case Report: Multimodal Imaging of Toxic Retinopathies Related to Human Immunodeficiency Virus Antiretroviral Therapies: Maculopathy vs. Peripheral Retinopathy. Report of Two Cases and Review of the Literature.Frontiers in neurology · 2021Article
- Ritonavir associated maculopathy- multimodal imaging and electrophysiology findings.American journal of ophthalmology case reports · 2020Article
- The Impact of Matrix Metalloproteinase-9 on the Sequential Steps of the Metastatic Process.International journal of molecular sciences · 2020Review
- Possible Retinal Impairment Secondary to Ritonavir Use in SARS-CoV-2 Patients: A Narrative Systematic Review.Journal of ophthalmology · 2020Review
- The Anti-Angiogenic Effects of Anti-Human Immunodeficiency Virus Drugs.Frontiers in oncology · 2020Review
- Inhibition of Obtusifolin on retinal pigment epithelial cell growth under hypoxia.International journal of ophthalmology · 2019Article
- HIF-1α-induced xenobiotic transporters promote Th17 responses in Crohn's disease.Journal of autoimmunity · 2018Article
- Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2018Article
- Electrophysiological features and multimodal imaging in ritonavir-related maculopathy.Documenta ophthalmologica. Advances in ophthalmology · 2017Article
- Prominin-1 Is a Novel Regulator of Autophagy in the Human Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2017Article
- Dickkopf‑related protein 1 induces angiogenesis by upregulating vascular endothelial growth factor in the synovial fibroblasts of patients with temporomandibular joint disorders.Molecular medicine reports · 2015Article
- Involvement of RhoA/ROCK1 signaling pathway in hyperglycemia-induced microvascular endothelial dysfunction in diabetic retinopathy.International journal of clinical and experimental pathology · 2014Article
- Retinopathy Associated With Ritonavir Treatment for HIV Infection: A Case Series Reappraisal in the COVID-19 Era.Journal of vitreoretinal diseasesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeRetinal hypoxia-mediated activation of the hypoxia-inducible factor (HIF pathway) leading to angiogenesis is a major signaling mechanism underlying a number of sight-threatening diseases. Inhibiting this signaling mechanism with an already approved therapeutic molecule may have promising anti-angiogenic role with fewer side effects. Hence, the primary objective of this study was to examine the expression of HIF-1α and VEGF in human retinal pigment epithelial cells treated with ritonavir under hypoxic and normoxic conditions.
methodsARPE-19 and D407 cells were cultured in normoxic or hypoxic conditions, alone or in the presence of ritonavir. Quantitative real-time polymerase chain reaction, immunoblot analysis, sandwich ELISA, endothelial cell proliferation, and cytotoxicity were performed.
resultsA 12-h hypoxic exposure resulted in elevated mRNA expression levels of both HIF-1α and VEGF in ARPE-19 and D407 cells. Hence, this time point was selected for subsequent experiments. Presence of ritonavir in the culture medium strongly inhibited VEGF expression in a concentration-dependent manner under hypoxic conditions. Immunoblot analysis demonstrated a substantially reduced protein expression of HIF-1α in the presence of ritonavir. Further, hypoxic exposure-induced VEGF secretion was also inhibited by ritonavir, as demonstrated using ELISA. Finally, ritonavir significantly diminished the proliferation of choroid-retinal endothelial (RF/6A) cells demonstrating potential anti-angiogenic activity. Cytotoxicity studies showed that ritonavir is non-toxic to RPE cells.
conclusionsThis study demonstrates for the first time that ritonavir can inhibit HIF-1α and VEGF in ARPE-19 and D407 cells. Such inhibition may form a platform for application of ritonavir in the treatment of various ocular diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.