An Atlas of Heparan Sulfate Proteoglycans in the Postnatal Rat Lens

Wishart, Tayler F.L.; Lovicu, Frank J.

doi:10.1167/iovs.62.14.5

Cited by 5 publications

(14 citation statements)

References 137 publications

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“…Although HSPGs are primarily composed of HS-GAGs, certain species such as syndecan-1/-3 [45,46], agrin [47], and collagen XVIII [48] may also carry CS-GAGs. Lens cells produce some proteoglycans carrying both HS-GAG and CS-GAG, although HS-GAG is the most common [35,49,50]. Consistent with this, here we report that HS-GAG, and not CS-GAG, is the predominant GAG associated with HSPGs throughout murine lens development.…”

Section: Discussionsupporting

confidence: 89%

“…Given the important role of HSPGs in regulating many growth factors, together with recent studies implicating HSPGs as essential for the induction and development of the eye, here we present the most comprehensive spatiotemporal labelling of all the different HSPG core proteins and their associated GAGs throughout murine lens development. This study complements and extends from our earlier report on the localisation of HSPGs in the postnatal rat lens [35], wherein we described how the defined patterns of all HSPGs associate with lens cellular activity. Of note is that our earlier study reported the absence of glypican 5 in the postnatal lens, of which we now have corrected and clearly show that it is indeed also present in the lens when using a more selective and effective commercial antibody.…”

Section: Discussionsupporting

confidence: 86%

“…Mid-sagittal sections of embryonic heads from at least three independent animals were used for immunolabelling and for periodic acid-Schiff's (PAS) staining to highlight lens morphology. Monoclonal antibodies were used to detect all highly sulphated HSPGs as previously described [35]. Embryonic head sections were first labelled for highly sulphated forms of HS-GAG (HS-GAG F58-10E4, 370255; Amsbio LLC, Abingdon, UK).…”

Section: Immunolabelling Of Heparan Sulphate Proteoglycansmentioning

confidence: 99%

“…As the activity of HSPGs primarily depends on its fine structure (i.e., sulphation) and location (i.e., the cell surface or ECM) of their HS-GAG glycosaminoglycan chains, the specific activity of HSPGs in a given cell-type or tissue, at a given time can be determined by its HSPG profile: the localisation of HSPG core proteins and its complement of HS-GAG sulfation enzymes [17,33]. Previously, we have shown all HSPG core proteins are present in the postnatal rat lens, localised to its epithelia, fibres and basement membrane, the lens capsule, in unique and distinct expression patterns that align with key functional regions [35]. The distinct spatial and temporal expression of HSPGs implies that differentiating lens cells may acquire a unique set of HSPGs, leading to specific patterns of HS-protein interactions and function during lens morphogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Spatiotemporal Localisation of Heparan Sulphate Proteoglycans throughout Mouse Lens Morphogenesis

Wishart

Lovicu

2023

Cells

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Heparan sulphate proteoglycans (HSPGs) consist of a core protein decorated with sulphated HS-glycosaminoglycan (GAG) chains. These negatively charged HS-GAG chains rely on the activity of PAPSS synthesising enzymes for their sulfation, which allows them to bind to and regulate the activity of many positively charged HS-binding proteins. HSPGs are found on the surfaces of cells and in the pericellular matrix, where they interact with various components of the cell microenvironment, including growth factors. By binding to and regulating ocular morphogens and growth factors, HSPGs are positioned to orchestrate growth factor-mediated signalling events that are essential for lens epithelial cell proliferation, migration, and lens fibre differentiation. Previous studies have shown that HS sulfation is essential for lens development. Moreover, each of the full-time HSPGs, differentiated by thirteen different core proteins, are differentially localised in a cell-type specific manner with regional differences in the postnatal rat lens. Here, the same thirteen HSPG-associated GAGs and core proteins as well as PAPSS2, are shown to be differentially regulated throughout murine lens development in a spatiotemporal manner. These findings suggest that HS-GAG sulfation is essential for growth factor-induced cellular processes during embryogenesis, and the unique and divergent localisation of different lens HSPG core proteins indicates that different HSPGs likely play specialized roles during lens induction and morphogenesis.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 86%

Section: Immunolabelling Of Heparan Sulphate Proteoglycansmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spatiotemporal Localisation of Heparan Sulphate Proteoglycans throughout Mouse Lens Morphogenesis

Wishart

Lovicu

2023

Cells

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“…An impressive number of mouse in vivo models exists that probe cell cycle-coupled differentiation of lens fiber cells using loss-of-function [ 235 , 266 , 267 , 268 , 269 , 270 ] and gain-of-function [ 271 , 272 , 273 , 274 , 275 ] models. Nevertheless, a number of open questions remain to be addressed that require large-scale protein purifications and analyses of protein–protein complexes and their post-translational modifications at different stages of the cell cycle, e.g., to probe formation of E2F-pRb [ 275 , 276 ], Pax6-pRb complexes [ 277 , 278 ], and interactions between FGF receptors, other membrane proteins, and their intracellular components [ 53 , 235 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 ]. Although dramatic progress with ChIP-seq methods using CUT&RUN, recently implemented in chicken lens studies [ 226 ], requires smaller number of cells, genome-wide analysis of lens chromatin occupancy by multiple DNA-binding transcription factors regulating these processes, including p53 [ 266 ], Gata3 [ 289 ], Hey1 [ 269 ], Prox1 [ 289 , 290 ], and Rbpj [ 291 , 292 , 293 ], can now be performed in parallel with analyses of modified histones and histone variants in chromatin isolated from micro-dissected lenses.…”

Section: 3d-eye Organoids: Experimental Challenges and In Vitro Model...mentioning

confidence: 99%

Generation of Lens Progenitor Cells and Lentoid Bodies from Pluripotent Stem Cells: Novel Tools for Human Lens Development and Ocular Disease Etiology

Cvekl

Camerino

2022

Cells

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In vitro differentiation of human pluripotent stem cells (hPSCs) into specialized tissues and organs represents a powerful approach to gain insight into those cellular and molecular mechanisms regulating human development. Although normal embryonic eye development is a complex process, generation of ocular organoids and specific ocular tissues from pluripotent stem cells has provided invaluable insights into the formation of lineage-committed progenitor cell populations, signal transduction pathways, and self-organization principles. This review provides a comprehensive summary of recent advances in generation of adenohypophyseal, olfactory, and lens placodes, lens progenitor cells and three-dimensional (3D) primitive lenses, “lentoid bodies”, and “micro-lenses”. These cells are produced alone or “community-grown” with other ocular tissues. Lentoid bodies/micro-lenses generated from human patients carrying mutations in crystallin genes demonstrate proof-of-principle that these cells are suitable for mechanistic studies of cataractogenesis. Taken together, current and emerging advanced in vitro differentiation methods pave the road to understand molecular mechanisms of cataract formation caused by the entire spectrum of mutations in DNA-binding regulatory genes, such as PAX6, SOX2, FOXE3, MAF, PITX3, and HSF4, individual crystallins, and other genes such as BFSP1, BFSP2, EPHA2, GJA3, GJA8, LIM2, MIP, and TDRD7 represented in human cataract patients.

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Clearing the light path: Proteoglycans and their important roles in the lens and cornea

Stepp,

Menko

2024

Proteoglycan Research

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Some of the earliest studies of glycans were performed on mammalian corneas and lenses with many of the key concepts we currently recognize as being fundamental to our understanding of basic cell biology arising from these studies. Proteoglycans and their glycosaminoglycan (GAG) side chains are essential components of the extracellular matrix (ECM) of the lens capsule. They also are present in the anterior corneal epithelial basement membrane and the posterior (Decemet's) basement membrane, and they organize collagen fiber diameters and spacing in the corneal stroma to maintain stromal clarity. Studies using genetically engineered mice and characterization of spontaneously arising mutations in genes controlling proteoglycan synthesis have generated new insight into the roles played by proteoglycans in signal transduction. We now know that proteoglycans and GAGs can regulate cell signaling and the maintenance of avascularity and immune privilege that are hallmarks of these tissues. In addition, proteoglycan‐rich matrices provide the pathways for immune cells to populate the surface of the lens as a response to corneal wounding and in a model of experimental autoimmune uveitis. Here we describe what is known about proteoglycans and GAGs in the cornea and lens. This knowledge has begun to provide promising leads into new proteoglycan‐based treatments aimed at restoring and maintaining homeostasis in the cornea. Future studies are needed to determine how these new drugs impact the recruitment of immune cells to the lens for functions in restoring/maintaining homeostasis in the eye.

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An Atlas of Heparan Sulfate Proteoglycans in the Postnatal Rat Lens

Cited by 5 publications

References 137 publications

Spatiotemporal Localisation of Heparan Sulphate Proteoglycans throughout Mouse Lens Morphogenesis

Spatiotemporal Localisation of Heparan Sulphate Proteoglycans throughout Mouse Lens Morphogenesis

Generation of Lens Progenitor Cells and Lentoid Bodies from Pluripotent Stem Cells: Novel Tools for Human Lens Development and Ocular Disease Etiology

Clearing the light path: Proteoglycans and their important roles in the lens and cornea

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