ArticleThe ocular surface2012
Elevated IGFBP3 levels in diabetic tears: a negative regulator of IGF-1 signaling in the corneal epithelium.
Article in The ocular surface, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- A systematic review on the impact of diabetes mellitus on the ocular surface.Nutrition & diabetes · 2017Pooled it
- Article
- Reversal of Diabetic Dry Eye by Topical Opioid Receptor Blockade Follows Dual Pathways.Investigative ophthalmology & visual science · 2025Article
- Review
- Diabetic Keratopathy: Redox Signaling Pathways and Therapeutic Prospects.Antioxidants (Basel, Switzerland) · 2024Review
- Elucidating the mechanism of corneal epithelial cell repair: unraveling the impact of growth factors.Frontiers in medicine · 2024Review
- The roles of autophagy and mitophagy in corneal pathology: current knowledge and future perspectives.Frontiers in medicine · 2023Review
- Autophagy in the normal and diseased cornea.Experimental eye research · 2022Review
- The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates.Cell death & disease · 2022Review
- IGFBP-3 Regulates Mitochondrial Hyperfusion and Metabolic Activity in Ocular Surface Epithelia during Hyperosmolar Stress.International journal of molecular sciences · 2022Article
- IGFBP-3 functions as a molecular switch that mediates mitochondrial and metabolic homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- IGFBP-3 Mediates Metabolic Homeostasis During Hyperosmolar Stress in the Corneal Epithelium.Investigative ophthalmology & visual science · 2021Article
- Systemic diseases and the cornea.Experimental eye research · 2021Review
- Diabetic Corneal Neuropathy.Journal of clinical medicine · 2020Review
- Orai-IGFBP3 signaling complex regulates high-glucose exposure-induced increased proliferation, permeability, and migration of human coronary artery endothelial cells.BMJ open diabetes research & care · 2020Article
- Tear Levels of IGFBP-3: A Potential Biomarker for Diabetic Nerve Changes in the Cornea.Eye & contact lens · 2020Review
- Tear biomarkers and corneal sensitivity as an indicator of neuropathy in type 2 diabetes.Diabetes research and clinical practice · 2020Article
- Eye care providers' emerging roles in early detection of diabetes and management of diabetic changes to the ocular surface: a review.BMJ open diabetes research & care · 2020Review
- Role of Insulin-Like Growth Factor Binding Protein-3 in the Pathogenesis of Herpes Stromal Keratitis.Investigative ophthalmology & visual science · 2020Article
- The IGF/Insulin-IGFBP Axis in Corneal Development, Wound Healing, and Disease.Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. Tear samples were collected noninvasively from diabetic subjects and non-diabetic controls; corneal sensitivity was assessed using a Cochet-Bonnet Aesthesiometer. Conditioned media were collected following culture of hTCEpi cells in normal (5 mM) and elevated (25 mM) glucose conditions; mannitol was used as an osmotic control. IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. IGFBP3 and IGF-1R mRNA were assessed by real-time polymerase chain reaction (PCR). Total and phosphorylated IGF-1R expression in whole cell lysates was assessed by western blot. There was a 2.8-fold increase in IGFBP3 in diabetic tears compared to non-diabetic controls (P=0.006); IGF-1 levels were not significantly altered. No difference in corneal sensitivity was detected between groups. The concentration of IGFBP3 in tears was independent of IGF-1. Consistent with human tear measurements in vivo, IGFBP3 secretion was increased 2.2 fold (P<0.001) following culture of hTCEpi cells under elevated glucose conditions in vitro. Treatment with glucose and the mannitol control reduced IGFBP3 mRNA (P<0.001). Total IGF-1R levels were unchanged. The increase in the IGFBP3:IGF-1 ratio detected in diabetic tears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (P<0.001) when tested in vitro. Taken together, these in vivo and confirmatory in vitro findings suggest that the observed increase in IGFBP3 found in human tears may attenuate IGF-1R signaling in the diabetic cornea. A long-term increase in IGFBP3 may contribute to epithelial compromise and the pathogenesis of ocular surface complications reported in diabetes.
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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.