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Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair.

ABSTRACT: 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.

SUBMITTER: Fouda AY

PROVIDER: S-EPMC9424300 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair.

Fouda Abdelrahman Y AY Xu Zhimin Z Suwanpradid Jutamas J Rojas Modesto M Shosha Esraa E Lemtalsi Tahira T Patel Chintan C Xing Ji J Zaidi Syed A SA Zhi Wenbo W Stansfield Brain K BK Cheng Paul Ning-Man PN Narayanan S Priya SP Caldwell R William RW Caldwell Ruth B RB

Cell death & disease 20220829 8

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 isc ...[more]

PMID: 36038541

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Project description:BackgroundDiabetic retinopathy (DR) is a leading cause of blindness due to diabetic macular edema (DME) or complications of proliferative diabetic retinopathy (PDR). Optical coherence tomography (OCT) is a noninvasive imaging technique well established for DME but less used to assess neovascularization in PDR. Developments in OCT imaging and the introduction of OCT angiography (OCTA) have shown significant potential in PDR.ObjectivesTo describe the tomographic features of PDR, namely of neovascularization, both of the optic disc (NVD) and elsewhere (NVE), intraretinal microvascular abnormalities (IRMA), retinal nonperfusion areas (NPA), status of the posterior vitreous, vitreoschisis and vitreous and subhyaloid/sub-ILM hemorrhages.Data sourcesElectronic database search on PubMed and EMBASE, last run on December 19th 2019.Study eligibility criteria participants and interventionsPublications assessing OCT and/or OCTA findings in PDR patients. All study designs were allowed except for case-reports, conference proceedings and letters.Study appraisalNewcastle-Ottawa Scale for observational studies was used for purposes of risk of bias assessment.ResultsFrom the 1300 studies identified, 283 proceeded to full-text assessment and 60 were included in this comprehensive review. OCT was useful in detecting NVD and NVE, such as in characterizing disease activity and response to laser and/or anti-VEGF therapies. The absence of posterior vitreous detachment seemed determinant for neovascular growth, with the posterior hyaloid acting as a scaffold. OCTA allowed a more detailed characterization of the neovascular complexes, associated NPA and disease activity, allowing the quantification of neovessel area and flow index. However, changes in OCTA blood flow signal following local therapies did not necessarily correlate with structural regression. Widefield and ultra-widefield OCTA were highly sensitive in the detection of PDR, adding value to disease staging and monitoring. Compared to fluorescein angiography, OCTA was more sensitive in detecting microvascular changes indicating disease progression.LimitationsPublication languages were restricted. Most included studies were observational and non-comparative. Risk of bias regarding case representativeness.ConclusionsOCT-based retinal imaging technologies are advancing rapidly and the trend is to be noninvasive and wide-field. OCT has proven invaluable in diagnosing, staging and management of proliferative diabetic disease with daily application in clinical and surgical practices.

Dataset Information

Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair.

Publications

Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair.

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