RGD Reference Report - Antiglaucomatous effects of the activation of intrinsic Angiotensin-converting enzyme 2. - Rat Genome Database

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Antiglaucomatous effects of the activation of intrinsic Angiotensin-converting enzyme 2.

Authors: Foureaux, G  Nogueira, JC  Nogueira, BS  Fulgencio, GO  Menezes, GB  Fernandes, SO  Cardoso, VN  Fernandes, RS  Oliveira, GP  Franca, JR  Faraco, AA  Raizada, MK  Ferreira, AJ 
Citation: Foureaux G, etal., Invest Ophthalmol Vis Sci. 2013 Jun 21;54(6):4296-306. doi: 10.1167/iovs.12-11427.
RGD ID: 9685447
Pubmed: PMID:23702784   (View Abstract at PubMed)
PMCID: PMC3739491   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.12-11427   (Journal Full-text)

PURPOSE: To evaluate the effects of the activation of endogenous angiotensin-converting enzyme 2 (ACE2) using the compound diminazene aceturate (DIZE) in an experimental model of glaucoma in Wistar rats. METHODS: DIZE (1 mg/kg) was administered daily, either systemically or topically, and the IOP was measured weekly. To examine the role of the Mas receptor in the effects of DIZE, the Ang-(1-7) antagonist A-779 was co-administered. Drainage of the aqueous humor was evaluated by using scintigraphy. The analysis of ACE2 expression by immunohistochemistry and the counting of retinal ganglion cells (RGCs) were performed in histologic sections. Additionally, the nerve fiber structure was evaluated by transmission electron microscopy. RESULTS: The systemic administration and topical administration (in the form of eye drops) of DIZE increased the ACE2 expression in the eyes and significantly decreased the IOP of glaucomatous rats without changing the blood pressure. Importantly, this IOP-lowering action of DIZE was similar to the effects of dorzolamide. The antiglaucomatous effects of DIZE were blocked by A-779. Histologic analysis revealed that the reduction in the number of RGCs and the increase in the expression of caspase-3 in the RGC layer in glaucomatous animals were prevented by DIZE. This compound also prevented alterations in the cytoplasm of axons in glaucomatous rats. In addition to these neuroprotective effects, DIZE facilitated the drainage of the aqueous humor. CONCLUSIONS: Our results evidence the pathophysiologic relevance of the ocular ACE2/Ang-(1-7)/Mas axis of the renin-angiotensin system and, importantly, indicate that the activation of intrinsic ACE2 is a potential therapeutic strategy to treat glaucoma.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glaucoma treatmentISOAce2 (Rattus norvegicus)9685447; 9685447 RGD 
glaucoma treatmentIDA 9685447 RGD 
glaucoma treatmentISOMas1 (Rattus norvegicus)9685447; 9685447 RGD 
glaucoma treatmentIMP 9685447 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ace2  (angiotensin converting enzyme 2)
Mas1  (MAS1 proto-oncogene, G protein-coupled receptor)

Genes (Mus musculus)
Ace2  (angiotensin converting enzyme 2)
Mas1  (MAS1 oncogene)

Genes (Homo sapiens)
ACE2  (angiotensin converting enzyme 2)
MAS1  (MAS1 proto-oncogene, G protein-coupled receptor)


Additional Information