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Induction of endothelial RAGE expression in pterygium.

Al-Swailem S, Xu Z, Wu L, Hartsock MJ, Yiu SC, Duh EJ - Mol. Vis. (2014)

Bottom Line: Tissue sections were analyzed with immunohistochemistry with anti-RAGE antibody.Other cell types exhibited expression, notably epithelial cells, fibroblasts, and possibly macrophages.RAGE upregulation is an important mechanism by which endothelial cells amplify the overall inflammatory response, and suppression of RAGE has been shown to prevent the progression of some systemic disease processes in experimental models.

View Article: PubMed Central - PubMed

Affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.

ABSTRACT

Purpose: Chronic inflammation is a critical process in pterygium development and progression, including promotion of angiogenesis. Vascular endothelial cells (ECs) actively participate in and regulate inflammation. Pterygium research has uncovered multiple inflammatory cytokines that are upregulated, but there has been minimal focus on EC activation. The Receptor for Advanced Glycation Endproducts (RAGE), a major proinflammatory molecule expressed in the vascular endothelium and other cell types, is a major instigator of endothelial cell activation. In this study, we explored the hypothesis that RAGE is upregulated in ECs in pterygium. To this end, we examined RAGE expression and immunolocalization in human pterygium and normal conjunctival tissue, with a particular interest in assessing endothelial RAGE.

Methods: Pterygium specimens were obtained from 25 patients during surgery at the King Khaled Eye Specialist Hospital (KKESH). In the same patients, conjunctiva were obtained from the autograft during surgery. Tissue specimens were formalin-fixed and paraffin-embedded. Tissue sections were analyzed with immunohistochemistry with anti-RAGE antibody. Expression and localization of RAGE were evaluated in pterygium and corresponding conjunctiva.

Results: RAGE expression was detected in the vascular endothelium in all pterygium tissue specimens and most conjunctival specimens. Other cell types exhibited expression, notably epithelial cells, fibroblasts, and possibly macrophages. Strikingly, endothelial RAGE expression was increased in 19 of 25 pterygium tissue specimens, compared to the corresponding control conjunctiva.

Conclusions: Our data reveal that RAGE expression is upregulated in vascular endothelial cells in pterygium. RAGE upregulation is an important mechanism by which endothelial cells amplify the overall inflammatory response, and suppression of RAGE has been shown to prevent the progression of some systemic disease processes in experimental models. This suggests that pharmacologic targeting of RAGE, which is already being attempted in clinical trials for some diseases, could be useful in treating pterygium.

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The expression of RAGE in human pterygium and normal conjunctiva tissues. A, B: Immunohistochemistry (IHC) staining of RAGE in conjunctiva and pterygium specimens. RAGE is expressed in endothelial cells lining the lumen of blood vessels (black arrows). In addition, other cell types also exhibit RAGE expression, notably epithelial cells (black arrow heads), fibroblasts (red arrows), and inflammatory cells (red arrow head). C, D: CD31 staining confirmed the distribution of microvascular endothelial cells in sections adjacent to the conjunctiva and pterygium samples used in A and B. E: Negative IHC staining in pterygium samples with control immunoglobulin G (IgG). The images were taken at 40X objective.
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f1: The expression of RAGE in human pterygium and normal conjunctiva tissues. A, B: Immunohistochemistry (IHC) staining of RAGE in conjunctiva and pterygium specimens. RAGE is expressed in endothelial cells lining the lumen of blood vessels (black arrows). In addition, other cell types also exhibit RAGE expression, notably epithelial cells (black arrow heads), fibroblasts (red arrows), and inflammatory cells (red arrow head). C, D: CD31 staining confirmed the distribution of microvascular endothelial cells in sections adjacent to the conjunctiva and pterygium samples used in A and B. E: Negative IHC staining in pterygium samples with control immunoglobulin G (IgG). The images were taken at 40X objective.

Mentions: We first investigated the localization of RAGE expression in pterygium, with specific interest in whether RAGE is expressed in vascular endothelial cells. RAGE expression in pterygium and conjunctival specimens was evaluated with immunohistochemical staining. In pterygium and conjunctiva, RAGE expression was detected in the epithelial layer in all specimens (Figure 1). In addition, RAGE was expressed in several cell types in the stroma, including fibroblasts, inflammatory cells, and vascular endothelial cells, as indicated by corresponding staining with the endothelial cell marker CD31/PECAM-1 (Figure 1). Of note, RAGE expression was consistently found in vascular endothelial cells in pterygium tissue, although to varying degrees (Figure 1; Table 2).


Induction of endothelial RAGE expression in pterygium.

Al-Swailem S, Xu Z, Wu L, Hartsock MJ, Yiu SC, Duh EJ - Mol. Vis. (2014)

The expression of RAGE in human pterygium and normal conjunctiva tissues. A, B: Immunohistochemistry (IHC) staining of RAGE in conjunctiva and pterygium specimens. RAGE is expressed in endothelial cells lining the lumen of blood vessels (black arrows). In addition, other cell types also exhibit RAGE expression, notably epithelial cells (black arrow heads), fibroblasts (red arrows), and inflammatory cells (red arrow head). C, D: CD31 staining confirmed the distribution of microvascular endothelial cells in sections adjacent to the conjunctiva and pterygium samples used in A and B. E: Negative IHC staining in pterygium samples with control immunoglobulin G (IgG). The images were taken at 40X objective.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279753&req=5

f1: The expression of RAGE in human pterygium and normal conjunctiva tissues. A, B: Immunohistochemistry (IHC) staining of RAGE in conjunctiva and pterygium specimens. RAGE is expressed in endothelial cells lining the lumen of blood vessels (black arrows). In addition, other cell types also exhibit RAGE expression, notably epithelial cells (black arrow heads), fibroblasts (red arrows), and inflammatory cells (red arrow head). C, D: CD31 staining confirmed the distribution of microvascular endothelial cells in sections adjacent to the conjunctiva and pterygium samples used in A and B. E: Negative IHC staining in pterygium samples with control immunoglobulin G (IgG). The images were taken at 40X objective.
Mentions: We first investigated the localization of RAGE expression in pterygium, with specific interest in whether RAGE is expressed in vascular endothelial cells. RAGE expression in pterygium and conjunctival specimens was evaluated with immunohistochemical staining. In pterygium and conjunctiva, RAGE expression was detected in the epithelial layer in all specimens (Figure 1). In addition, RAGE was expressed in several cell types in the stroma, including fibroblasts, inflammatory cells, and vascular endothelial cells, as indicated by corresponding staining with the endothelial cell marker CD31/PECAM-1 (Figure 1). Of note, RAGE expression was consistently found in vascular endothelial cells in pterygium tissue, although to varying degrees (Figure 1; Table 2).

Bottom Line: Tissue sections were analyzed with immunohistochemistry with anti-RAGE antibody.Other cell types exhibited expression, notably epithelial cells, fibroblasts, and possibly macrophages.RAGE upregulation is an important mechanism by which endothelial cells amplify the overall inflammatory response, and suppression of RAGE has been shown to prevent the progression of some systemic disease processes in experimental models.

View Article: PubMed Central - PubMed

Affiliation: King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.

ABSTRACT

Purpose: Chronic inflammation is a critical process in pterygium development and progression, including promotion of angiogenesis. Vascular endothelial cells (ECs) actively participate in and regulate inflammation. Pterygium research has uncovered multiple inflammatory cytokines that are upregulated, but there has been minimal focus on EC activation. The Receptor for Advanced Glycation Endproducts (RAGE), a major proinflammatory molecule expressed in the vascular endothelium and other cell types, is a major instigator of endothelial cell activation. In this study, we explored the hypothesis that RAGE is upregulated in ECs in pterygium. To this end, we examined RAGE expression and immunolocalization in human pterygium and normal conjunctival tissue, with a particular interest in assessing endothelial RAGE.

Methods: Pterygium specimens were obtained from 25 patients during surgery at the King Khaled Eye Specialist Hospital (KKESH). In the same patients, conjunctiva were obtained from the autograft during surgery. Tissue specimens were formalin-fixed and paraffin-embedded. Tissue sections were analyzed with immunohistochemistry with anti-RAGE antibody. Expression and localization of RAGE were evaluated in pterygium and corresponding conjunctiva.

Results: RAGE expression was detected in the vascular endothelium in all pterygium tissue specimens and most conjunctival specimens. Other cell types exhibited expression, notably epithelial cells, fibroblasts, and possibly macrophages. Strikingly, endothelial RAGE expression was increased in 19 of 25 pterygium tissue specimens, compared to the corresponding control conjunctiva.

Conclusions: Our data reveal that RAGE expression is upregulated in vascular endothelial cells in pterygium. RAGE upregulation is an important mechanism by which endothelial cells amplify the overall inflammatory response, and suppression of RAGE has been shown to prevent the progression of some systemic disease processes in experimental models. This suggests that pharmacologic targeting of RAGE, which is already being attempted in clinical trials for some diseases, could be useful in treating pterygium.

Show MeSH
Related in: MedlinePlus