Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
29 08 2022
29 08 2022
Historique:
received:
16
02
2022
accepted:
17
08
2022
revised:
15
08
2022
entrez:
29
8
2022
pubmed:
30
8
2022
medline:
1
9
2022
Statut:
epublish
Résumé
Current therapies for treatment of proliferative retinopathy focus on retinal neovascularization (RNV) during advanced disease and can trigger adverse side-effects. Here, we have tested a new strategy for limiting neurovascular injury and promoting repair during early-stage disease. We have recently shown that treatment with a stable, pegylated drug form of the ureohydrolase enzyme arginase 1 (A1) provides neuroprotection in acute models of ischemia/reperfusion injury, optic nerve crush, and ischemic stroke. Now, we have determined the effects of this treatment on RNV, vascular repair, and retinal function in the mouse oxygen-induced retinopathy (OIR) model of retinopathy of prematurity (ROP). Our studies in the OIR model show that treatment with pegylated A1 (PEG-A1), inhibits pathological RNV, promotes angiogenic repair, and improves retinal function by a mechanism involving decreased expression of TNF, iNOS, and VEGF and increased expression of FGF2 and A1. We further show that A1 is expressed in myeloid cells and areas of RNV in retinal sections from mice with OIR and human diabetic retinopathy (DR) patients and in blood samples from ROP patients. Moreover, studies using knockout mice with hemizygous deletion of A1 show worsened RNV and retinal injury, supporting the protective role of A1 in limiting the OIR-induced pathology. Collectively, A1 is critically involved in reparative angiogenesis and neuroprotection in OIR. Pegylated A1 may offer a novel therapy for limiting retinal injury and promoting repair during proliferative retinopathy.
Identifiants
pubmed: 36038541
doi: 10.1038/s41419-022-05196-8
pii: 10.1038/s41419-022-05196-8
pmc: PMC9424300
doi:
Substances chimiques
Polyethylene Glycols
3WJQ0SDW1A
Arginase
EC 3.5.3.1
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
745Subventions
Organisme : BLRD VA
ID : I01 BX001233
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY031631
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY029318
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY011766
Pays : United States
Organisme : NEI NIH HHS
ID : R00 EY029373
Pays : United States
Informations de copyright
© 2022. The Author(s).
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