Different responses of the MIO­M1 Mueller cell line to angiotensin II under hyperglycemic or hypoxic conditions.

Members of the renin-angiotensin aldosterone system (RAAS) are expressed by various retinal tissues including Mueller glial cells. As the RAAS is hypothesized to play an important role in the pathogenesis of diseases that threaten vision, such as diabetic macular edema or retinal vein occlusion, the possible changes induced by exposure of the human cell line MIO-M1, an established model of Mueller cells, to angiotensin II or aldosterone for 6 h under hypoxic and/or hyperglycemic conditions were investigated. The mRNA expression levels of the members of the RAAS were assessed by reverse transcription-quantitative PCR, and the secretion of cytokines was assessed by ELISA. Under hyperglycemic conditions, the mRNA expression levels of the angiotensin-converting enzyme 2 (ACE2), angiotensin II receptors, AT1 and AT2, and the receptor of angiotensin (1-7) MAS1 were significantly higher after exposure to angiotensin II, and the expression of ACE2, AT2, and IL-6 (a marker of inflammation) was significantly increased after treatment with aldosterone; the expression of the other targets investigated remained unchanged. Significantly more IL-6 was secreted by MIO-M1 cells exposed to hyperglycemia and angiotensin. When cells were cultured in a hypoxic environment, additional treatment with aldosterone significantly increased the mRNA expression levels of ACE, but significantly more ACE2 mRNA was expressed in the presence of angiotensin II. Under hypoxic plus hyperglycemic conditions, significantly less ACE but more AT2 was expressed after treatment with angiotensin II, which also led to strongly elevated expression of IL-6. The mRNA expression levels of the angiogenic growth factor VEGF-A and secretion of the encoded protein were notably increased under hypoxic and hypoxic plus hyperglycemic conditions, irrespective of additional treatment with angiotensin II or aldosterone. These findings suggest that angiotensin II induces a pro-inflammatory response in MIO-M1 cells under hyperglycemic conditions despite activation of the counteracting ACE2/MAS1 signaling cascade. However, hypoxia results in an increased expression of angiogenic VEGF-A by these cells, which is not altered by angiotensin II or aldosterone.

[Use of antiglaucomatous drugs in the urban adult population : New Insights into the prevalence of glaucoma from the Hamburg City Health Study]. / Anwendung von Antiglaukomatosa in der urbanen erwachsenen Bevölkerung : Erkenntnisse zur Glaukomprävalenz aus der Hamburg City Health Study.

BACKGROUND: Glaucoma is a widespread ophthalmological disease. Knowledge about the spread of the disease in the population is necessary with respect to further questions on comorbidities, risk factors and the provision of care. OBJECTIVE: An analysis of the use of glaucoma medications and the prevalence of glaucoma in an urban adult population was carried out. MATERIAL AND METHODS: The Hamburg City Health Study (HCHS) is a prospective, long-term, population-based cohort study that includes a random sample of 45,000 participants aged between 45 and 79 years from the general population of Hamburg, Germany. Apart from various medical parameters, data include premedication and the medical history of the participants. The use of antiglaucomatous medication among the first 10,000 study participants was analyzed and the prevalence of glaucoma was estimated according to the use of medications as well as by the self-reported history of glaucoma. Descriptive analysis and logistic regression analysis were performed to analyze the data and to calculate correlations by age and gender. RESULTS: In the study population 319 persons were on medication to lower the intraocular pressure (IOP, mean age 67.1 years, SD = 7.57 years), which is equivalent to an estimated prevalence of 3.35% (95% confidence interval, CI 3.00-3.70%). A positive correlation was observed between age and the use of IOP-lowering medication, which is statistically highly significant (p = < 0.001). The analysis by gender showed a slightly higher prevalence among women, which was not statistically significant. The estimated prevalence according to glaucoma medication and history were only partly congruent. DISCUSSION: This estimated prevalence of glaucoma is comparable to other epidemiological studies. The study results cover not only patients with manifest glaucoma but also persons who were treated for ocular hypertension. The inconsistency between the prevalence of glaucoma medication and the diagnosis of glaucoma can be explained by different treatment strategies and also by information deficits.