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

Abstract

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.

VEGF mRNA Assessment in Human Pterygium: A New ‘Scope' for a Future Hope

“…By applying this in situ hybridization-based method for VEGF mRNA quantification, we were able to correlate with more accuracy the VEGF mRNA amplification with the cellular and fibrovascular compartments of human pterygium. The absence of VEGF mRNA amplification in the fibrovascular compartment and its presence confirmed by in situ hybridization in the epithelial compartment, which was only found in the present study, contradict previous reports regarding VEGF immunohistochemical expression in both epithelial and fibrovascular compartments [10]. The lack of VEGF mRNA amplification in the fibrovascular compartment suggests a false positive immunohistochemical reaction and sustains the addition of RNAscope as a validation method for immunohistochemistry in human pterygium evaluation.…”

“…The lack of powerful evidence to support the efficacy of anti-VEGF therapy in human pterygium treatment can be attributed to incomplete VEGF expression assessment in human pterygium specimens by restrictive use of immunohistochemistry only and failure to use the molecular methods able to confirm immunohistochemical findings [10]. Only one paper reported the VEGF-460C polymorphism associated with pterygium formation in female patients [11].…”

Cytokine Expression in Keratoconus and its Corneal Microenvironment: A Systematic Review

“…Both are wellknown sources of cytokine production and resident immune cells. 98,[127][128][129] As described in Section III, numerous proteases, immunoglobulins, and cytokines have been found in tear fluid of patients with KC, which could reflect changes in lacrimal gland and conjunctiva. The conjunctiva can suffer from severe immune dysregulation with detrimental effects on the ocular surface, as has been shown in diseases such as allergic conjunctivitis.…”

“…The conjunctiva can suffer from severe immune dysregulation with detrimental effects on the ocular surface, as has been shown in diseases such as allergic conjunctivitis. [127][128][129] It is not hard to imagine that cytokines in the tear fluid associated with KC may be derived in part from the conjunctiva or lacrimal glands, and are not only a consequence of corneal pathology.…”

Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation

“…Indeed, under inflammatory and hypoxic conditions these glial cells secrete factors such as VEGF, that increase the vascular permeability [2,56], and matrix metalloproteinases [10,36], which impair the barrier function of retinal endothelial cells. Under normoxic conditions, Müller cells secrete pigment epithelium-derived factor (PEDF) that decreases the barrier permeability and downregulates the expression of VEGF [12,22]. VEGF is known to modulate immune responses by increasing vascular permeability.…”