Adeno-Associated Virus Overexpression of Angiotensin-Converting Enzyme-2 Reverses Diabetic Retinopathy in Type 1 Diabetes in Mice

dc.contributor.authorDominguez, James M., II
dc.contributor.authorHu, Ping
dc.contributor.authorCaballero, Sergio
dc.contributor.authorMoldovan, Leni
dc.contributor.authorVerma, Amrisha
dc.contributor.authorOudit, Gavin Y.
dc.contributor.authorLi, Qiuhong
dc.contributor.authorGrant, Maria B.
dc.contributor.departmentDepartment of Ophthalmology, School of Medicineen_US
dc.date.accessioned2017-11-06T18:37:34Z
dc.date.available2017-11-06T18:37:34Z
dc.date.issued2016
dc.description.abstractAngiotensin-converting enzyme (ACE)-2 is the primary enzyme of the vasoprotective axis of the renin angiotensin system that regulates the classic renin angiotensin system axis. We aimed to determine whether local retinal overexpression of adenoassociated virus (AAV)-ACE2 prevents or reverses diabetic retinopathy. Green fluorescent protein (GFP)-chimeric mice were generated to distinguish resident (retinal) from infiltrating bone marrow-derived inflammatory cells and were made diabetic using streptozotocin injections. Retinal digestion using trypsin was performed and acellular capillaries enumerated. Capillary occlusion by GFP(+) cells was used to measure leukostasis. Overexpression of ACE2 prevented (prevention cohort: untreated diabetic, 11.3 ± 1.4; ACE2 diabetic, 6.4 ± 0.9 per mm(2)) and partially reversed (reversal cohort: untreated diabetic, 15.7 ± 1.9; ACE2 diabetic, 6.5 ± 1.2 per mm(2)) the diabetes-associated increase of acellular capillaries and the increase of infiltrating inflammatory cells into the retina (F4/80(+)) (prevention cohort: untreated diabetic, 24.2 ± 6.7; ACE2 diabetic, 2.5 ± 1.6 per mm(2); reversal cohort: untreated diabetic, 56.8 ± 5.2; ACE2 diabetic, 5.6 ± 2.3 per mm(2)). In both study cohorts, intracapillary bone marrow-derived cells, indicative of leukostasis, were only observed in diabetic animals receiving control AAV injections. These results indicate that diabetic retinopathy, and possibly other diabetic microvascular complications, can be prevented and reversed by locally restoring the balance between the classic and vasoprotective renin angiotensin system.en_US
dc.eprint.versionFinal published version
dc.identifier.citationDominguez, J. M., Hu, P., Caballero, S., Moldovan, L., Verma, A., Oudit, G. Y., … Grant, M. B. (2016). Adeno-Associated Virus Overexpression of Angiotensin-Converting Enzyme-2 Reverses Diabetic Retinopathy in Type 1 Diabetes in Mice. The American Journal of Pathology, 186(6), 1688–1700. http://doi.org/10.1016/j.ajpath.2016.01.023en_US
dc.identifier.urihttps://hdl.handle.net/1805/14455
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.ajpath.2016.01.023en_US
dc.relation.journalAmerican Journal of Pathologyen_US
dc.sourcePMCen_US
dc.subjectAngiotensin converting enzymeen_US
dc.subjectMiceen_US
dc.subjectDiabetic retinopathyen_US
dc.titleAdeno-Associated Virus Overexpression of Angiotensin-Converting Enzyme-2 Reverses Diabetic Retinopathy in Type 1 Diabetes in Miceen_US
dc.typeArticleen_US
ul.alternative.fulltexthttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901140/en_US
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