ArticleMatrix biology : journal of the International Society for Matrix Biology2021
Latent-transforming growth factor beta-binding protein-2 (LTBP-2) is required for longevity but not for development of zonular fibers.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Charting the Phenotypic Landscape of FBN1 Variants in Marfan Syndrome With Ectopia Lentis Through Extreme Phenotype Sampling.Investigative ophthalmology & visual science · 2026Article
- Mitochondrial insufficiencies and neuroprotection in glaucoma.International ophthalmology · 2026Review
- Serial Aqueous Humor Proteomics in Diabetic Macular Edema: Correlation of Novel Targets with Retinal Fluid Volume.Ophthalmology science · 2026Article
- Ciliary Zonule of the Human Eye: Structural and Mechanical Aspects.Investigative ophthalmology & visual science · 2026Article
- Single zonular fiber extraction and characterization: A platform for biomechanical, biochemical and structural analyses.Experimental eye research · 2026Article
- Review
- A Single Cell Atlas of the Newt Iris During Lens Regeneration.bioRxiv : the preprint server for biology · 2025Article
- Phenotype-driven clustering of ocular manifestations reveals prognostic and genetic heterogeneity in Marfan syndrome: a real-world longitudinal cohort study.Journal of translational medicine · 2025Article
- Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure.Scientific reports · 2025Article
- Healthy Aging Metabolomic and Proteomic Signatures Across Multiple Physiological Compartments.Aging cell · 2025Article
- Genetic factors underlying Mandibular prognathism: insights from recent human and animal studies.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort.Human genomics · 2025Article
- Characterization of LTBP2 mutation causing mitral valve prolapse.European heart journal open · 2025Article
- Article
- Review
- Alterations in anterior lens capsule structure and LTBP-2 expression in primary angle-closure glaucoma.BMJ open ophthalmology · 2024Article
- Multi-organ phenotypes in mice lacking latent TGFβ binding protein 2 (LTBP2).Developmental dynamics : an official publication of the American Association of Anatomists · 2024Review
- A Novel Multi-Observation System to Study the Effects of Anterior Ocular Inflammation in Zinn's Zonule Using One Specimen.International journal of molecular sciences · 2023Article
- Extracellular matrix and vascular dynamics in the kidney of a murine model for Marfan syndrome.PloS one · 2023Article
- Fibrillin-1 Regulates Arteriole Integrity in the Retina.Biomolecules · 2022Article
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11 authors at 5 institutions in 3 countries.
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Abstract
Latent-transforming growth factor beta-binding protein 2 (LTBP-2) is a major component of arterial and lung tissue and of the ciliary zonule, the system of extracellular fibers that centers and suspends the lens in the eye. LTBP-2 has been implicated previously in the development of extracellular microfibrils, although its exact role remains unclear. Here, we analyzed the three-dimensional structure of the ciliary zonule in wild type mice and used a knockout model to test the contribution of LTBP-2 to zonule structure and mechanical properties. In wild types, zonular fibers had diameters of 0.5-1.0 micrometers, with an outer layer of fibrillin-1-rich microfibrils and a core of fibrillin-2-rich microfibrils. LTBP-2 was present in both layers. The absence of LTBP-2 did not affect the number of fibers, their diameters, nor their coaxial organization. However, by two months of age, LTBP-2-depleted fibers began to rupture, and by six months, a fully penetrant ectopia lentis phenotype was present, as confirmed by in vivo imaging. To determine whether the seemingly normal fibers of young mice were compromised mechanically, we compared zonule stress/strain relationships of wild type and LTBP-2-deficient mice and developed a quasi-linear viscoelastic engineering model to analyze the resulting data. In the absence of LTBP-2, the ultimate tensile strength of the zonule was reduced by about 50%, and the viscoelastic behavior of the fibers was altered significantly. We developed a harmonic oscillator model to calculate the forces generated during saccadic eye movement. Model simulations suggested that mutant fibers are prone to failure during rapid rotation of the eyeball. Together, these data indicate that LTBP-2 is necessary for the strength and longevity of zonular fibers, but not necessarily for their formation.
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