Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy
Pigment epithelium-derived factor (PEDF), an endogenous Wnt signaling inhibitor in the serine proteinase inhibitors (SERPIN) super family, is present in multiple organs, including the vitreous. Significantly low levels of PEDF in the vitreous are found to associate with pathological retinal vascular...
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| Format: | Article |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.1049678/full |
| _version_ | 1828090410430365696 |
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| author | Qiang Qu Kyoungmin Park Kevin Zhou Drew Wassel Rafal Farjo Tracy Criswell Jian-xing Ma Yuanyuan Zhang |
| author_facet | Qiang Qu Kyoungmin Park Kevin Zhou Drew Wassel Rafal Farjo Tracy Criswell Jian-xing Ma Yuanyuan Zhang |
| author_sort | Qiang Qu |
| collection | DOAJ |
| description | Pigment epithelium-derived factor (PEDF), an endogenous Wnt signaling inhibitor in the serine proteinase inhibitors (SERPIN) super family, is present in multiple organs, including the vitreous. Significantly low levels of PEDF in the vitreous are found to associate with pathological retinal vascular leakage and inflammation in diabetic retinopathy (DR). Intravitreal delivery of PEDF represents a promising therapeutic approach for DR. However, PEDF has a short half-life after intravitreal injection, which represents a major hurdle for the long-term treatment. Here we report the prolonged therapeutic effects of a 34-mer peptide of the PEDF N-terminus, encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEDF34-NP), on DR. PEDF34-NP inhibited hypoxia-induced expression of vascular endothelial growth factor and reduced levels of intercellular adhesion molecule 1 (ICAM-1) in cultured retinal cells. In addition, PEDF34-NP significantly ameliorated ischemia-induced retinal neovascularization in the oxygen-induced retinopathy rat model, and significantly reduced retinal vascular leakage and inflammation in streptozotocin-induced diabetic rats up to 4 weeks after intravitreal injection, as compared to PLGA-NP control. Intravitreal injection of PEDF34-NP did not display any detectable toxicities to retinal structure and function. Our findings suggest that PEDF34-NP can confer sustained therapeutic effects on retinal inflammation and vascular leakage, having considerable potential to provide long-term treatment options for DR. |
| first_indexed | 2024-04-11T05:57:01Z |
| format | Article |
| id | doaj.art-eecfdf07ae8f495991c732a11ae649eb |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T05:57:01Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-eecfdf07ae8f495991c732a11ae649eb2022-12-22T04:41:52ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-12-011010.3389/fcell.2022.10496781049678Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathyQiang Qu0Kyoungmin Park1Kevin Zhou2Drew Wassel3Rafal Farjo4Tracy Criswell5Jian-xing Ma6Yuanyuan Zhang7Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaJoslin Diabetes Center, Harvard Medical School, Boston, MA, United StatesDepartment of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, United StatesEyeCro LLC., Oklahoma City, OK, United StatesEyeCro LLC., Oklahoma City, OK, United StatesInstiture for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United StatesDepartment of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, United StatesInstiture for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United StatesPigment epithelium-derived factor (PEDF), an endogenous Wnt signaling inhibitor in the serine proteinase inhibitors (SERPIN) super family, is present in multiple organs, including the vitreous. Significantly low levels of PEDF in the vitreous are found to associate with pathological retinal vascular leakage and inflammation in diabetic retinopathy (DR). Intravitreal delivery of PEDF represents a promising therapeutic approach for DR. However, PEDF has a short half-life after intravitreal injection, which represents a major hurdle for the long-term treatment. Here we report the prolonged therapeutic effects of a 34-mer peptide of the PEDF N-terminus, encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEDF34-NP), on DR. PEDF34-NP inhibited hypoxia-induced expression of vascular endothelial growth factor and reduced levels of intercellular adhesion molecule 1 (ICAM-1) in cultured retinal cells. In addition, PEDF34-NP significantly ameliorated ischemia-induced retinal neovascularization in the oxygen-induced retinopathy rat model, and significantly reduced retinal vascular leakage and inflammation in streptozotocin-induced diabetic rats up to 4 weeks after intravitreal injection, as compared to PLGA-NP control. Intravitreal injection of PEDF34-NP did not display any detectable toxicities to retinal structure and function. Our findings suggest that PEDF34-NP can confer sustained therapeutic effects on retinal inflammation and vascular leakage, having considerable potential to provide long-term treatment options for DR.https://www.frontiersin.org/articles/10.3389/fcell.2022.1049678/fullpigment epithelium-derived factoranti-inflammatoryanti-vascular leakagediabetic retinopathywnt signalingPLGA |
| spellingShingle | Qiang Qu Kyoungmin Park Kevin Zhou Drew Wassel Rafal Farjo Tracy Criswell Jian-xing Ma Yuanyuan Zhang Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy Frontiers in Cell and Developmental Biology pigment epithelium-derived factor anti-inflammatory anti-vascular leakage diabetic retinopathy wnt signaling PLGA |
| title | Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy |
| title_full | Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy |
| title_fullStr | Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy |
| title_full_unstemmed | Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy |
| title_short | Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy |
| title_sort | sustained therapeutic effect of an anti inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy |
| topic | pigment epithelium-derived factor anti-inflammatory anti-vascular leakage diabetic retinopathy wnt signaling PLGA |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.1049678/full |
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