Angiogenesis in pterygium: study of microvessel density, vascular endothelial growth factor, and thrombospondin-1

Aspiotis, Miltiadis; Tsanou, Elena; Gorezis, Spiridon; Ioachim, Elli; Skyrlas, Angelos; Stefaniotou, Maria; Malamou-Mitsi, Vasiliki

doi:10.1038/sj.eye.6702495

Cited by 101 publications

(92 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, it seems that VEGF buildup in the epithelial cells is only a reflection of their secretory capacity, while build-up in the endothelial and stromal cells reflects its angiogenic activity. In this respect, Aspiotis M et al demonstrated a higher vascular microdensity in the fibrous subtype than in the vascular type, thus confirming the assumption that stroma plays a role in the pathogenesis of pterygium (29). Furthermore, the presence of proinflammatory cytokines secreted from the surface epithelium or from lacrimal inflammatory cells induces the fibroblastic production of proteins related to remodelling of extracellular matrix and angiogenesis.…”

Section: Discussionsupporting

confidence: 52%

Immunohistochemical Profile and VEGF, TGF-β and PGE₂ in Human Pterygium and Normal Conjunctiva: Experimental Study and Review of the Literature

Bianchi¹,

Scarinci

Grande³

et al. 2012

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

Human pterygium is made up of chronic proliferative fibro-vascular tissue growing on the ocular surface. This disease exhibits both degenerative and hyperplastic properties. Some fibroangiogenic factors have recently been shown to play a potential role in fibrovascular diseases via the angiogenesis process. The aim of this study is to evaluate VEGF, TGF-β and PGE2 expression in the epithelial, endothelial and stromal cells of human pterygium and normal conjunctiva in order to determine whether these factors participate in the development of pterygium. Ten specimens from patients with pterygium and two normal conjunctivas (cadavers) were analyzed by immunohistochemistry using specific antibodies against these growth factors. The technique used was ABC/HRP (Avidin complexed with biotinylated peroxidase). Immunoreactivity of VEGF was significantly increased in the epithelium, vascular endothelium and stromal cells in primary pterygium as compared with normal conjunctiva. A moderate expression of TGF-β in the pterygium was observed in the epithelial and stromal layers. On the contrary, immunolabeling of this growth factor in the human normal conjunctiva was weak. PGE2 was strongly expressed in the epithelium of patients with pterygium, as in control conjunctival tissues, and the immunolabeling was moderate in the stroma from the same patients. Our results suggest that these growth factors may contribute to the progression of primary pterygium by increasing angiogenesis, thus leading to the formation of new blood vessels from the pre-existing vasculature. We conclude that VEGF, TGF-β and PGE2 may be potential therapeutic targets in the treatment of this disease although proof of this evidence requires further studies.

show abstract

Section: Discussionsupporting

confidence: 52%

Immunohistochemical Profile and VEGF, TGF-β and PGE₂ in Human Pterygium and Normal Conjunctiva: Experimental Study and Review of the Literature

Bianchi¹,

Scarinci

Grande³

et al. 2012

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

show abstract

“…7 Moreover, TSP-1-deficient mice spontaneously develop conjunctival inflammation with age. 22 Regarding TSP-1 expression in human conjunctiva, some studies reported a mild and focal TSP-1 staining in normal human conjunctival epithelium, 23 while others reported detection of the protein in corneal, but not in conjunctival epithelia, 24,25 suggesting a pivotal role of TSP-1 in preventing corneal angiogenesis. A reported correlation between a polymorphism in the TSP-1 gene (THBS-1) and chronic ocular surface inflammation in humans further supports the importance of TSP-1 in immunomodulation.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Soriano-Romaní

Contreras-Ruiz

García-Posadas

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Purpose: Increased expression of transforming growth factor-b2 (TGF-b2) is reported in the conjunctiva of dry eye patients with no increase of anti-inflammatory activity of TGF-b2. Our aim was to compare the expression of molecules involved in TGF-b2 activation, thrombospondin-1 (TSP-1) and CD36, during murine and human conjunctival inflammation. Methods: Human conjunctival tissue from cadaveric donors, human conjunctival epithelial primary cells and fibroblasts, and murine conjunctivas were immunostained for TSP-1, CD36, or TGF-b2. Inflamed conjunctival tissues were obtained from C57BL/6 wild-type (WT) mice induced to develop experimental dry eye (EDE) with 10 days of desiccating conditions and scopolamine injections and TSP-1-deficient (TSP1 -/ -) mice, which spontaneously develop Sjögren's syndrome-associated conjunctival inflammation with age. Immunostaining intensities were compared using ImageJ software. Cultures of human conjunctival fibroblasts were stimulated with IL-1b and both secreted protein and message levels of TSP-1, CD36, and TGF-b2 were analyzed. Results: TSP-1 and CD36 were detectable in human and murine conjunctival tissues as well as primary conjunctival epithelial cells and fibroblasts. Increased conjunctival immunostaining of TGF-b2 and reduced CD36 were detected in EDE mice compared with WT mice. Interestingly, increased TGF-b2 and CD36 conjunctival immunostaining was detected in TSP1-/ -mice. The expression of TSP-1 and CD36 was downregulated in IL-1b-stimulated conjunctival fibroblasts at both the protein and message level, while active TGFb2 was undetected. Conclusions: The absence or reduced expression of either of the molecules involved in TGF-b2 activation supports proinflammatory conditions in the conjunctiva. Changes in TSP-1 and CD36 may serve as potential biomarkers of conjunctival inflammation.

show abstract

“…A few studies that differentiated primary and recurrent pterygia reported that the levels of VEGF, basic fibroblast growth factor, and substance P were significantly higher in recurrent disease (9) . Markers for vascular endothelial cells such as CD31+ are increased in pterygium, which supports angiogenesis (10) . A higher number of CD34 cells -a mast cell marker -in recurrent versus primary pterygium has also been reported (11) .…”

Section: Introductionmentioning

confidence: 89%

“…Ribatti et al reported that mast cells are involved in the angiogenesis of pterygium, which could be one of the reasons for their development (7) . Aspiotis et al noted that the density of microvessels in pterygium was significantly higher than in normal conjunctiva, and that the overexpression of VEGF was among the most potent angiogenic factors (10) . The number of mast cells in pterygium is higher than that in normal conjunctiva (5,6) .…”

Section: Discussionmentioning

confidence: 99%

The role of mast cells in vascularized recurrent pterygium

Çelebi¹,

Özbey²,

Mirza³

2014

Arquivos Brasileiros De Oftalmologia

View full text Add to dashboard Cite

Objective: To determine and compare the mast cell count in primary and recurrent vascularized pterygium, and in normal bulbar conjunctiva. Methods: The study included 22 patients with primary pterygium (PP group) and 28 patients with vascularized recurrent pterygium (VRP group) that underwent excision via the limbal conjunctival autograft technique. Normal conjunctiva samples were collected from the superotemporal bulbar conjunctival region, just temporal to the site from which the autograft conjunctival tissue was harvested. The total number of mast cells in the pterygium (primary and recurrent) and control tissue samples was calculated microscopically using 1% toluidine blue stain under 400× magnification. Results:The mean mast cell count in primary and vascularized recurrent pterygium tissue was 7.45 ± 2.06 mm -2 and 16.11 ± 4.33 mm -2 , respectively, and the difference was significant (independent samples t-test, P<0.001). The mean mast cell count in pterygium tissue was significantly higher than that in normal conjunctiva tissue in both groups (Student's t-test, P<0.001). Conclusion: An increase in the number of mast cells might play a role in the pathogenesis of recurrent pterygium. Determination of a mast cell count cut-off value could be of diagnostic significance for recurrent pterygium.

show abstract

Angiogenesis in pterygium: study of microvessel density, vascular endothelial growth factor, and thrombospondin-1

Cited by 101 publications

References 32 publications

Immunohistochemical Profile and VEGF, TGF-β and PGE₂ in Human Pterygium and Normal Conjunctiva: Experimental Study and Review of the Literature

Immunohistochemical Profile and VEGF, TGF-β and PGE₂ in Human Pterygium and Normal Conjunctiva: Experimental Study and Review of the Literature

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

The role of mast cells in vascularized recurrent pterygium

Contact Info

Product

Resources

About

Angiogenesis in pterygium: study of microvessel density, vascular endothelial growth factor, and thrombospondin-1

Cited by 101 publications

References 32 publications

Immunohistochemical Profile and VEGF, TGF-β and PGE2 in Human Pterygium and Normal Conjunctiva: Experimental Study and Review of the Literature

Immunohistochemical Profile and VEGF, TGF-β and PGE2 in Human Pterygium and Normal Conjunctiva: Experimental Study and Review of the Literature

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

The role of mast cells in vascularized recurrent pterygium

Contact Info

Product

Resources

About

Immunohistochemical Profile and VEGF, TGF-β and PGE₂ in Human Pterygium and Normal Conjunctiva: Experimental Study and Review of the Literature

Immunohistochemical Profile and VEGF, TGF-β and PGE₂ in Human Pterygium and Normal Conjunctiva: Experimental Study and Review of the Literature