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.
Background Alpha-1-antitrypsin is a protein involved in avoidance of different processes that are seen in diabetic retinopathy pathogenesis. These processes include apoptosis, extracellular matrix remodeling and damage of vessel walls and capillaries. Furthermore, because of its antiinflammatory effects, alpha-1-antitrypsin has been proposed as a possible therapeutic approach for diabetic retinopathy. Our group tested alpha-1-antitrypsin in a type 1 diabetes mouse model and observed a reduction of inflammation and retinal neurodegeneration. Thus, shedding light on the mechanism of action of alpha-1-antitrypsin at molecular level may explain how it works in the diabetic retinopathy context and show its potential for use in other retinal diseases. Methods In this work, we evaluated alpha-1-antitrypsin in an ARPE-19 human cell line exposed to high glucose. We explored the expression of different mediators on signaling pathways related to pro-inflammatory cytokines production, glucose metabolism, epithelial-mesenchymal transition and other proteins involved in the normal function of retinal pigment epithelium by RT-qPCR and Western Blot. Results We obtained different expression patterns for evaluated mediators altered with high glucose exposure and corrected with the use of alpha-1-antitrypsin.
The COVID-19 pandemic has forced all nations to take an active role in infection control incorporating recommendations and measures to control viral dissemination. The epidemiological impact is very diverse and dynamic, even within the same region. Scientific knowledge regarding SARS-CoV-2 continues to improve every day with protocols needing to be updated and adjusted on a regular basis. Ophthalmology is a medical specialty identified to be at high risk for several reasons: it has very close doctor-patient contact, the virus has been detected in tears, and the ocular surface serves as a gateway to developing the infection. We have reviewed the current information on SARS-CoV-2 in the ophthalmologic field and provide up-to-date recommendations to help create protocols that can adapt to the dynamic situation of ophthalmologic institutions, patient cases, economic situations and access to diagnostic tests. This paper outlines the main recommendations regarding the initial consultation and outpatient clinics, measures to apply in the operating room (OR), and suggestions for post-surgical controls. Triage, according to the patient's conditions and eye pathology, reduction of the time the patient is at the institution, social distancing, correct use of personal protective equipment (PPE), barrier methods, hygiene, as well as other recommendations mentioned in this document, will allow physicians to take care of the visual health of the patients while reducing the impact of the COVID-19 pandemic.
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