Melatonin prevents blood-retinal barrier breakdown and mitochondrial dysfunction in high glucose and hypoxia-induced in vitro diabetic macular edema model.

Diabetic macular edema (DME) is a leading cause of blindness in diabetic retinopathy. Prolonged hyperglycemia plus hypoxia contributes to DME pathogenesis. Retinal pigmented epithelial cells comprise the outer blood-retinal barrier and are essential for maintaining physiological functioning of the retina. Melatonin acts as an antioxidant and regulator of mitochondrial bioenergetics and has a protective effect against ocular diseases. However, the role of mitochondrial dysfunction and the therapeutic potential of melatonin in DME remain largely unexplored. Here, we used an in vitro model of DME to investigate blood-retinal barrier integrity and permeability, angiogenesis, mitochondrial dynamics, and apoptosis signaling to evaluate the potential protective efficacy of melatonin in DME. We found that melatonin prevents cell hyper-permeability and outer barrier breakdown by reducing HIF-1α, HIF-1ß and VEGF and VEGF receptor gene expression. In addition, melatonin reduced the expression of genes involved in mitochondrial fission (DRP1, hFis1, MIEF2, MFF), mitophagy (PINK, BNip3, NIX), and increased the expression of genes involved in mitochondrial biogenesis (PGC-1α, NRF2, PPAR-γ) to maintain mitochondrial homeostasis. Moreover, melatonin prevented apoptosis of retinal pigmented epithelial cells. Our results suggest that mitochondrial dysfunction may be involved in DME pathology, and melatonin may have therapeutic value in DME, by targeting signaling in mitochondria.

In spontaneous intracerebral hematoma patients, prediction of the hematoma expansion risk and mortality risk using radiological and clinical markers and a newly developed scale.

Objective: In patients with spontaneous intracerebral hematoma (ICH), early-stage hematoma expansion has been associated with poor prognosis in literature. This study aimed to develop predictive parameter(s) as well as a new scale to define hematoma expansion and short-term prognosis in patients with ICH.Methods: In 46 patients with ICH, Glasgow Coma Scale (GCS) scores, non-contrast CT (NCCT) markers (hematoma volume on admission and follow-up, hypodensity, intraventricular hemorrhage, blend and island sign, BAT score), and modified Rankin Scale scores were evaluated for predicting the hematoma expansion risk and mortality risk. Furthermore, a newly developed scale called the 'HEMRICH scale' was constituted using the GCS score, hematoma volumes, and some NCCT markers.Results: Roc-Curve and Logistic Regression test results revealed that GCS score, initial hematoma volume value, hypodensity, intraventricular haemorrhage, BAT score, and HEMRICH scale score could be the best markers in predicting hematoma expansion risk whereas GCS score, intraventricular haemorrhage, BAT score, hematoma expansion, and HEMRICH scale score could be the best markers in predicting mortality risk (p = 0.01). Moreover, Factor analysis and Reliability test results showed that HEMRICH scale score could predict both hematoma expansion and mortality risks validly (Kaiser-Meyer-Olkin test value = 0.729) and reliably (Cronbach's alpha = 0.564).Conclusion: It was concluded that the GCS score, intraventricular haemorrhage, and BAT score could predict both hematoma expansion risk and mortality risk in the early stage in patients with ICH. Furthermore, it was suggested that the newly produced HEMRICH scale could be a valid and reliable scale for predicting both hematoma expansion and mortality risk.