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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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Related in: MedlinePlus

Increased RAGE expression in vascular endothelial cells in human primary pterygium compared to corresponding conjunctiva samples. RAGE staining in pterygium (A) and conjunctiva (B) samples from case 4. RAGE staining in pterygium (C) and conjunctiva (D) samples from case 5. RAGE staining in pterygium (E) and conjunctiva (F) samples from case 6. RAGE staining in pterygium (G) and conjunctiva (H) samples from case 24. RAGE staining in pterygium (I) and conjunctiva (J) samples from case 25. Black arrows indicate vascular endothelial cells. The images were taken at 40X objective.
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f2: Increased RAGE expression in vascular endothelial cells in human primary pterygium compared to corresponding conjunctiva samples. RAGE staining in pterygium (A) and conjunctiva (B) samples from case 4. RAGE staining in pterygium (C) and conjunctiva (D) samples from case 5. RAGE staining in pterygium (E) and conjunctiva (F) samples from case 6. RAGE staining in pterygium (G) and conjunctiva (H) samples from case 24. RAGE staining in pterygium (I) and conjunctiva (J) samples from case 25. Black arrows indicate vascular endothelial cells. The images were taken at 40X objective.

Mentions: Among 20 primary pterygium cases, in 16 patients (80%), the RAGE levels were increased in the vasculature compared to the corresponding conjunctiva (Table 2; Figure 2). In five recurrent pterygium cases, three cases exhibited increased expression of endothelial RAGE (Table 2; Figure 3). Because of the small number of recurrent pterygium cases, the correlation between RAGE expression and disease stage (primary versus recurrent) could not be determined.


Induction of endothelial RAGE expression in pterygium.

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

Increased RAGE expression in vascular endothelial cells in human primary pterygium compared to corresponding conjunctiva samples. RAGE staining in pterygium (A) and conjunctiva (B) samples from case 4. RAGE staining in pterygium (C) and conjunctiva (D) samples from case 5. RAGE staining in pterygium (E) and conjunctiva (F) samples from case 6. RAGE staining in pterygium (G) and conjunctiva (H) samples from case 24. RAGE staining in pterygium (I) and conjunctiva (J) samples from case 25. Black arrows indicate vascular endothelial cells. 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

f2: Increased RAGE expression in vascular endothelial cells in human primary pterygium compared to corresponding conjunctiva samples. RAGE staining in pterygium (A) and conjunctiva (B) samples from case 4. RAGE staining in pterygium (C) and conjunctiva (D) samples from case 5. RAGE staining in pterygium (E) and conjunctiva (F) samples from case 6. RAGE staining in pterygium (G) and conjunctiva (H) samples from case 24. RAGE staining in pterygium (I) and conjunctiva (J) samples from case 25. Black arrows indicate vascular endothelial cells. The images were taken at 40X objective.
Mentions: Among 20 primary pterygium cases, in 16 patients (80%), the RAGE levels were increased in the vasculature compared to the corresponding conjunctiva (Table 2; Figure 2). In five recurrent pterygium cases, three cases exhibited increased expression of endothelial RAGE (Table 2; Figure 3). Because of the small number of recurrent pterygium cases, the correlation between RAGE expression and disease stage (primary versus recurrent) could not be determined.

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