Month: 16 May 2016
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Gene therapy using angiotensin-converting enzyme 2 reverses diabetic retinopathy in animal model
Research, conducted at the University of Florida College of Medicine, has shown that adeno-associated viral (AAV) delivery of angiotensin-converting enzyme (ACE)-2 is capable of preventing and partially reversing diabetic retinopathy in models of type-1 diabetes. The finding provides encouraging data for the development of therapeutic opportunities to tackle a global public health challenge expected to severely stretch national health services over the coming decades. Diabetic retinopathy (DR) is estimated to occur in 30% of diabetic patients with 5–10% suffering proliferative DR and diabetic macular edema (DME). The size of the challenge has been illustrated in a recent meta-analysis of 35 population-based studies which report that > 90 million people are estimated to have DR, 21 million have DME and 17 million have proliferative DR.
The gene therapy research, conducted at the Department of Pharmacology and Therapeutics, and the Department of Ophthalmology and Powell Gene Therapy Center at University of Florida, delivered AAV-ACE-2 to the retina of normal murine models that were subsequently made diabetic with streptozoticin and to models that had already developed diabetes for over 6 months. The different cohorts allowed the researchers to test the ability of the therapy to alter the diabetic phenotype as it developed and also to test the potential for reversing the disease when it was established. According to the research team, the delivered therapeutic, ACE-2, is the “primary enzyme of the vasoprotective axis of the renin angiotensin system (RAS) that regulates the classic renin angiotensin system axis.” As such, over-expression of the enzyme was expected to act by opposing the classic RAS converting the proinflammatory / vasoconstrictive Ang II into the anti-inflammatory / vasodilatory Ang(1-7).
According to the research team, the current study was the first to show a potential therapy to reverse DR in the presence of persistent untreated hyperglycemia. The study indicated that over-expression of ACE-2 prevented and reversed the diabetes-induced increase of macrophages / microglia and prevented the increase of macroglia immunoreactivity. In addition, the therapy prevented and reversed the occurrence of leukostasis. In conclusion, the researchers comment that, “the results of this set of studies provide further support for the hypothesis that an imbalance between the two axes of the RAS is a key initial event that leads to development of diabetic microvascular complications. The use of AAV-ACE2 via intravitreal injection may represent a novel strategy for DR in humans and should be considered as a possible therapeutic approach for other microvascular and macrovascular complications of diabetes.”Back to previous