Abstract
Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.Electronic supplementary materialThe online version of this article (doi:10.1186/0717-6287-47-58) contains supplementary material, which is available to authorized users.
Highlights
The overall prevalence of diabetic retinopathy (DR) in diabetic patients is about 34% worldwide and it is the leading cause of blindness in the working population (16–64 years old) [1]
It was found a positive correlation between vitreous levels of might release metalloproteases (MMPs)-9 and vascular endothelial growth factor (VEGF) with proliferative DR [75], and levels of Alpha-1 antitrypsin (AAT) were found increased in different types of vitreoretinal diseases [76]
Through these mechanisms described above AAT might protect the structures of the vessel walls of retinal capillaries that are damaged in DR development
Summary
The overall prevalence of diabetic retinopathy (DR) in diabetic patients is about 34% worldwide and it is the leading cause of blindness in the working population (16–64 years old) [1]. In the retina of diabetic rats the activation of cytosolic MMP-9 and MMP-2 is an early event, which is followed by their accumulation in the mitochondria [74] In humans, it was found a positive correlation between vitreous levels of MMP-9 and VEGF with proliferative DR [75], and levels of AAT were found increased in different types of vitreoretinal diseases [76]. We previously pointed out the capacity of AAT to inhibit protease-activated receptors, to diminish neutrophil chemotaxis, to hinder NFkB activation, to reduce the effect of TNF-alpha and to inhibit caspases Through these mechanisms described above AAT might protect the structures of the vessel walls of retinal capillaries that are damaged in DR development.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
