Browsing by Author "Almeida, Maria Joana Valente Mesquita de"
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- Investigational studies of human vitreous and serum VEGF-A, VEGF-B and PIGFPublication . Almeida, Maria Joana Valente Mesquita de; Tomaz, Cândida Ascensão Teixeira; Sousa, João Paulo Castro de; Passarinha, Luís António PaulinoVascular Endothelium Growth Factors (VEGFs) are important regulators of endothelium cell proliferation, migration, and permeability not only during embryonic vasculogenesis but also in physiological and pathological angiogenesis. The VEGF family comprises seven members, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F, and Placental Growth Factor (PIGF); each one has a unique expression, specificity, and function. These members with different physical and biological properties act through three specific receptor tyrosine kinases, VEGFR-1, VEGFR-2, VEGFR-3, and two semaphorins receptors neuropilin-1 (NRP-1) and NRP-2. Almost 80% of the volume of the eye is made up of a clear gel-like substance called vitreous humor that fills the center of the eye and is in continuous contact with the retina. It consists of water (~99%), hyalocytes, hyaluronic acid, ascorbic acid, inorganic salts, glucose, and a network of collagen fibrils. In the present study, three cytokines (VEGF-A, VEGF-B and PIGF) were investigated in vitreous humor and serum of patients with ocular pathology, measured by Enzyme-linked immunosorbent assay (ELISA). To compare and characterize the quantitative results obtained by ELISA, the patients were categorized into two groups: 1. Patients with neovascular ocular diseases were categorized into the following subgroups: age-related macular degeneration (AMD), retinal vein occlusion (RVO), and diabetic retinopathy (DR) patients and 2. Patients with non-neovascular ocular diseases: vitreomacular traction syndrome patients of idiopathic etiology or rhegmatogenous retinal detachment patients. Additionally, the growth factors were compared or correlated between: 1. The studied groups of patients; 2. The different ocular pathologies; 3. With patient baseline clinical characteristics such as naïve vs. non-naive patients, previous treatments, the presence of glaucoma, and stage of diabetic retinopathy (non-proliferative diabetic retinopathy vs. proliferative diabetic retinopathy). For further investigation, serum and vitreous concentration levels of VEGF-A, VEGF-B, and PIGF were correlated between each other and between changes assessed by optical coherence tomography (OCT) and visual acuity (VA) measurements. The major conclusions of this study were as follows: 1. VEGF-A, VEGF-B, and PIGF vitreous levels are overexpressed in patients with neovascular ocular diseases in comparison with patients with non-neovascular ocular diseases; 2. In diabetic patients the vitreous vascular endothelial growth factors levels increase with the progression of the disease, being lower in non-proliferative diabetic retinopathy patients and higher in proliferative diabetic retinopathy patients. However, serum levels of VEGF-A, VEGF-B and PIGF were higher in non-proliferative diabetic retinopathy patients in comparison with proliferative diabetic retinopathy patients; 3. There were no statistical differences between the concentration values of serum VEGF-A, VEGF-B or PIGF between neovascular and non-neovascular diseases; 4. There was a positive and strong correlation between vitreous and serum VEGF-A and VEGF-B, suggesting a simultaneous pathological increase in those cytokines; 5. There was no correlation between serum levels and vitreous levels of all growth factors: VEGF-A, VEGF-B and PIGF; 6. There was a correlation between VEGF A or VEGF-B and macular volume; 7. Through the descriptive analysis of previous treatments as well as the comparative analysis between naïve and non-naïve patients, the existence of patients with insufficient response to the current therapies was confirmed, and therefore, there is an unmet need for the research of new drugs to treat neovascular ocular diseases. Taken altogether, these results suggest an overexpression of vitreous levels for the three studied cytokines. The correlations between VEGF-A and VEGF-B growth factors confirmed they may be simultaneously increased in neovascular eye pathologies. The correlations with diabetic retinopathy stage as well with structural and functional characteristics of studied neovascular disorders demonstrated the action of these cytokines in the progression of the disease. Targeting VEGF-A or VEGF-B or PIGF inhibition may have beneficial and impactful implications in the treatment of neovascular diseases, not only in terms of better outcomes but also in the regression of disease (in the case of diabetes). The identification of serum markers or other disease characteristics is easily measurable. Their correlation with vitreous levels will also lead to early intervention in disease prevention through the detention of ocular neovascularization before the appearance of clinical symptoms, subsequently leading to the prevention of blindness.