Small Leucine-Rich Proteoglycans (SLRPs) in the Retina

Low, Shermaine W. Y.; Connor, Thomas B.; Kassem, Iris S.; Costakos, Deborah M.; Chaurasia, Shyam S.

doi:10.3390/ijms22147293

Cited by 16 publications

(12 citation statements)

References 90 publications

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“…A proteomics study of postmortem human eyes revealed that lumican was also found in Bruch's membrane, the choroid, and neurosensory retinae [30], where it was highly associated with ERM's origin. Due to being a member of the class II small leucine-rich proteoglycan (SLRP) family, lumican can maintain retinal homeostasis, is involved in collagen fibrillogenesis, and regulates proinflammatory responses [31]. Animal studies also proved increased expression of lumican along with age and modifications of lumican by macrophages, neutrophils, and polymorphonuclear neutrophils in immune responses [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study

et al. 2022

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Idiopathic epiretinal membrane (iERM) is a pathological fibrocellular change in the vitreoretinal junction over the macular area; however, possible pathogenic mechanisms remain unclear. Changes in the differential protein composition of the aqueous humor (AH) may represent potential molecular changes associated with iERM. To gain new insights into the molecular mechanisms of iERM pathology, a sensitive label-free proteomics analysis was performed to compare AH protein expressions in patients with cataracts with or without iERM. This study employed nanoflow ultra-high-performance liquid chromatography-tandem mass spectrometry to investigate protein compositions of the AH obtained from individual human cataract eyes from 10 patients with iERM and 10 age-matched controls without iERM. Eight proteins were differentially expressed between the iERM and control samples, among which six proteins were upregulated and two were downregulated. A gene ontology (GO) analysis revealed that iERM was closely associated with several biological processes, such as immunity interactions, cell proliferation, and extracellular matrix remodeling. Additionally, multiple proteins, including lumican, cyclin-dependent kinase 13, and collagen alpha-3(VI) chain, were correlated with the central retinal thickness, indicating a multifactorial response in the pathogenic process of iERM. Changes in the AH level of lumican between iERM and control samples were also confirmed by an enzyme-linked immunosorbent assay. In conclusion, several pathological pathways involved in iERM were identified in the AH by a proteomic analysis, including immune reactions, cell proliferation, and remodeling of the extracellular matrix. Lumican is a potential aqueous biomarker for predicting iERM development and monitoring its progression. More clinical parameters also need to be identified to complete the analysis, and those could provide additional targets for treating and preventing iERM.

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Section: Discussionmentioning

confidence: 99%

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study

et al. 2022

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“…Intravitreal injection of decorin significantly inhibits laser induced CNV in a rodent model [ 223 ]. Decorin might exhibit anti-angiogenic responses by acting as an inhibitor for multiple receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR), the insulin-like growth factor receptor (IGFR), and the Met hepatocyte growth factor receptor [ 224 ]. It has also been shown to decrease hypoxia-induced VEGF expression by blocking the Met expression pathway and downregulating the Ras-related C3 botulinum toxin substrate and HIF1-α [ 224 ].…”

Section: Damps In Retinal Disordersmentioning

confidence: 99%

“…Decorin might exhibit anti-angiogenic responses by acting as an inhibitor for multiple receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR), the insulin-like growth factor receptor (IGFR), and the Met hepatocyte growth factor receptor [ 224 ]. It has also been shown to decrease hypoxia-induced VEGF expression by blocking the Met expression pathway and downregulating the Ras-related C3 botulinum toxin substrate and HIF1-α [ 224 ]. Additionally, the RPE cells with a high-risk genotype at 10q26 for AMD showed significantly enhanced versican expression in the ECM [ 206 ].…”

Section: Damps In Retinal Disordersmentioning

confidence: 99%

“…Decorin binds to TGFβ with high affinity and is known for its anti-fibrotic role compared to traditional anti-fibrotic adjuvants such as mitomycin-C and 5-fluorouracil [ 286 , 287 ]. Nevertheless, it has both pro-and anti-angiogenic properties [ 224 ]. Similarly, anti-angiogenic therapeutic DAMPs such as LIF, HS, and IL-33 are also in the early stages and their safety and efficacy profile is awaited for retinal disorders.…”

Section: Therapeutic Implications Of Dampsmentioning

confidence: 99%

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Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders

Mahaling

Low

Beck

et al. 2022

IJMS

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Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from the extracellular and intracellular space of damaged tissue or dead cells. Recent evidence indicates that DAMPs are associated with the sterile inflammation caused by aging, increased ocular pressure, high glucose, oxidative stress, ischemia, mechanical trauma, stress, or environmental conditions, in retinal diseases. DAMPs activate the innate immune system, suggesting their role to be protective, but may promote pathological inflammation and angiogenesis in response to the chronic insult or injury. DAMPs are recognized by specialized innate immune receptors, such as receptors for advanced glycation end products (RAGE), toll-like receptors (TLRs) and the NOD-like receptor family (NLRs), and purine receptor 7 (P2X7), in systemic diseases. However, studies describing the role of DAMPs in retinal disorders are meager. Here, we extensively reviewed the role of DAMPs in retinal disorders, including endophthalmitis, uveitis, glaucoma, ocular cancer, ischemic retinopathies, diabetic retinopathy, age-related macular degeneration, rhegmatogenous retinal detachment, proliferative vitreoretinopathy, and inherited retinal disorders. Finally, we discussed DAMPs as biomarkers, therapeutic targets, and therapeutic agents for retinal disorders.

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“…The interest in exploring N -glycans’ role in AMD stems from the understanding that various proteoglycans have a role in retinal development and functioning [ 20 , 21 , 22 ], suggesting that their manipulation may even have beneficial therapeutic effects [ 23 ]. This was seen for NA3, a tri-antennary glycan without sialic acid, which was implied as having a protective role in AMD pathogenesis [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

N-Glycosylation Patterns across the Age-Related Macular Degeneration Spectrum

et al. 2022

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The pathogenesis of age-related macular degeneration (AMD) remains elusive, despite numerous research studies. Therefore, we aimed to investigate the changes of plasma and IgG-specific N-glycosylation across the disease severity spectrum. We examined 2835 subjects from the 10.001 Dalmatians project, originating from the isolated Croatian islands of Vis and Korčula. All subjects were classified into four groups, namely (i) bilateral AMD, (ii) unilateral AMD, (iii) early-onset drusen, and (iv) controls. We analysed plasma and IgG N-glycans measured by HPLC and their association with retinal fundus photographs. There were 106 (3.7%) detected cases of AMD; 66 of them were bilateral. In addition, 45 (0.9%) subjects were recorded as having early-onset retinal drusen. We detected several interesting differences across the analysed groups, suggesting that N-glycans can be used as a biomarker for AMD. Multivariate analysis suggested a significant decrease in the immunomodulatory bi-antennary glycan structures in unilateral AMD (adjusted odds ratio 0.43 (95% confidence interval 0.22–0.79)). We also detected a substantial increase in the pro-inflammatory tetra-antennary plasma glycans in bilateral AMD (7.90 (2.94–20.95)). Notably, some of these associations were not identified in the aggregated analysis, where all three disease stages were collapsed into a single category, suggesting the need for better-refined phenotypes and the use of disease severity stages in the analysis of more complex diseases. Age-related macular degeneration progression is characterised by the complex interplay of various mechanisms, some of which can be detected by measuring plasma and IgG N-glycans. As opposed to a simple case-control study, more advanced and refined study designs are needed to understand the pathogenesis of complex diseases.

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Small Leucine-Rich Proteoglycans (SLRPs) in the Retina

Cited by 16 publications

References 90 publications

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study

Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders

N-Glycosylation Patterns across the Age-Related Macular Degeneration Spectrum

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