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K.M. Falkenhagen, V. Lanier, R.M. Braziel, C.R. White, J.T. Rosenbaum, J.R. Smith; Expression of Vascular Endothelial Growth Factor and Receptors in Acne Rosacea . Invest. Ophthalmol. Vis. Sci. 2006;47(13):598.
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© ARVO (1962-2015); The Authors (2016-present)
Acne rosacea is a common, but poorly understood dermatological condition that may cause facial disfigurement, blepharitis and vision–threatening keratoconjunctivitis despite a variety of therapeutic interventions. Skin lesions include papules, pustules and small vessel abnormalities. The angiogenic protein, vascular endothelial growth factor (VEGF), is expressed in other skin and ocular surface inflammations. We immunostained skin biopsies from patients with rosacea to investigate the possibility that VEGF and receptors, VEGF–R1 and VEGF–R2, contributed to the pathogenesis of the disease.
Skin biopsies previously obtained from 20 patients (M:F, 7:13; 31–82 years) to make the diagnosis of acne rosacea, and skin taken from a normal individual during bariatric surgery, were studied. 3 micron sections of formalin–fixed, paraffin–embedded tissue were stained separately with hematoxylin and eosin, and by an indirect immunohistochemical method, using antibodies to VEGF (rabbit polyclonal, 2.5 µg/mL), VEGF–R1 (rabbit polyclonal, 2.5 µg/mL) and VEGF–R2 (mouse monoclonal, 1 µg/mL). Negative control sections were stained with rabbit IgG or irrelevant mouse monoclonal antibody. Antigen retrieval was achieved by boiling sections for 10 minutes in citrate buffer (pH 6.0).
Biopsies from patients with acne rosacea were characterized by perivascular and perifollicular lymphohistiocytic infiltration and dilated blood vessels; in severe cases granulomas and microabcesses were visible. In normal skin, epidermis and the epithelium of eccrine and apocrine glands stained positively for VEGF, VEGF–R1 and VEGF–R2. VEGF–R1 was also expressed by normal endothelium. Examination of the biopsies revealed that, in addition to epithelial staining, vascular endothelium frequently stained positively for VEGF–R1 (14/20, 70%) and VEGF–R2 (20/20, 100%), but infrequently for VEFG (2/20, 10%). In most specimens, filtrating lymphocytes, macrophages and plasma cells expressed VEFG (17/20, 85%), VEGF–R1 (20/20, 100%) and VEGF–R2 (20/20, 100%). Neutrophils were notably VEGF and receptor negative.
Expression of VEGF receptors, both by vascular endothelium and within perifollicular and perivascular mononuclear infiltrates, is observed in acne rosacea. Although not expressed by endothelium, VEGF is present in epidermis and epithelium of the skin appendages. VEGF receptor–ligand binding could contribute to the vascular changes and cellular infiltration characteristic of rosacea.
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