Mechanistic Insight into Age-Related Macular Degeneration (AMD): Anatomy, Epidemiology, Genetics, Pathogenesis, Prevention, Implications, and Treatment Strategies to Pace AMD Management.

One of the most complicated eye disorders is age-related macular degeneration (AMD) which is the leading cause of irremediable blindness all over the world in the elderly. AMD is classified as early stage to late stage (advanced AMD), in which this stage is divided into the exudative or neovascular form (wet AMD) and the nonexudative or atrophic form (dry AMD). Clinically, AMD primarily influences the central area of retina known as the macula. Importantly, the wet form is generally associated with more severe vision loss. AMD has a systemic component, where many factors, like aging, genetic, environment, autoimmune and non-autoimmune disorders are associated with this disease. Additionally, healthy lifestyles, regular exercise, maintaining a normal lipid profile and weight are crucial to decreasing the risk of AMD. Furthermore, therapeutic strategies for limiting AMD should encompass a variety of factors to avoid and improve drug interventions, and also need to take into account personalized genetic information. In conclusion, with the development of technology and research progress, visual impairment and legal blindness from AMD have been substantially reduced in incidence. This review article is focused on identifying and developing the knowledge about the association between genetics, and etiology with AMD. We hope that this review will encourage researchers and lecturers, open new discussions, and contribute to a better understanding of AMD that improves patients' visual acuity, and upgrades the quality of life of AMD patients.

Comparison of miRNA signature versus conventional biomarkers before and after off-pump coronary artery bypass graft.

Circulating levels of microRNAs (miRNAs) and their expression patterns are supposed to serve as signatures for diagnosis or prognosis of cardiovascular events. The present study aimed at determining if there is any correlation between the release pattern of 2 miRNAs and the plasma levels of conventional biomarkers cardiac troponin I (cTnI), creatine kinase (CK) and uric acid (UA) in patients undergoing their first off-pump coronary artery bypass graft (OCABG). Seventy OCABG patients (69% men, aged 59.2±8.2years) were enrolled. Emergencies, re-operations, abnormal preoperative serum cTnI and combined procedures were excluded from this study. Pre-operative mean ejection fraction was 45.8±8.6%, the average number of grafts was 3±0.87/patient, and the internal mammary artery was used for all. Beside conventional clinical assays, we performed real-time quantitative PCR to analyze the circulating levels of miR-155, miR-126 and miR-499 at 1day before surgery as well as 4days after surgery. Importantly, there was no report of myocardial infarction in our patients, pre- or post-operatively. In contrast to conventional biomarkers cTnI and CK, circulating levels of miRNAs decreased significantly (P<0.01) after revascularization surgery. A significant positive correlation was seen between the cTnI and miR-499 (r∼0.53, P<0.01) and between miR-126 and UA (r∼0.5, P<0.01). Time course study of circulating miR-499, miR-126 and miR-155 in cardiac surgery clarified their advantage and correlations to the traditional biomarkers cTnI, total CK, CK-MB and UA. Our results suggest that this signature is a novel, early biomarker which indicates myocardial ischemia in cardiac surgery. It could be postulated that the application of these miRNAs may be considered for monitoring of response to pharmacological interventions aimed at reducing cardiac ischemia, especially in OCABG candidates.

Circulating miR-126 and miR-499 reflect progression of cardiovascular disease; correlations with uric acid and ejection fraction.

BACKGROUND: The aim of this study was to assess plasma levels of endothelium- and heart-associated microRNAs (miRNAs) miR-126 and miR-499, respectively, using quantitative reverse transcriptase polymerase chain reaction. METHODS: A two-step analysis was conducted on 75 patients undergoing off-pomp coronary artery bypass graft (CABG) surgery. Five biomarkers of inflammation and cardiac injury were assessed in addition to the above-mentioned miRNAs. RESULTS: Plasma concentrations of miRNAs were found to be significantly correlated with plasma levels of cardiac troponin I (cTnI) (miR-499, r 0.49, p~0.002; miR-126, r = 0.30, p~0.001), indicating cardiac damage. Data analysis revealed that miR-499 had higher sensitivity and specificity for cardiac injury than miR-126, which reflects more endothelial activation. Interestingly, a strong correlation was observed between both miRNAs and uric acid (UA) levels with ventricular contractility measured as ejection fraction (EF) (miR-499/EF%, r = 0.58, p~0.004; UA/EF%, r = -0.6, p~0.006; UA/miR-499, r = -0.34; UA/miR-126, r = 0.5, p~0.01). CONCLUSIONS: In patients undergoing CABG, circulating miR-126/499 is associated with presentation of traditional risk factors and reflects post-operative response to injury. Plasma pool of miRNAs likely reflects extracellular miRNAs which are proportional to intracellular miRNA levels. Therefore, circulating levels of these miRNAs have prognostic implications in detection of higher risk of future cardiovascular events.