Preclinical Efficacy of Pro- and Anti-Angiogenic Peptide Hydrogels to Treat Age-Related Macular Degeneration
Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea®). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the contr...
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| Published in | Bioengineering (Basel) Vol. 8; no. 12; p. 190 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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MDPI AG
23.11.2021
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| ISSN | 2306-5354 2306-5354 |
| DOI | 10.3390/bioengineering8120190 |
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| Abstract | Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea®). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness. Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept. Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period. |
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| AbstractList | Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea®). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness. Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept. Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period. Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea®). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness. Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept. Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period.Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea®). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness. Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept. Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period. Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea ). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness. Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept. Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period. Pro-angiogenic and anti-angiogenic peptide hydrogels were evaluated against the standard of care wet age-related macular degeneration (AMD) therapy, Aflibercept (Eylea ® ). AMD was modeled in rats (laser-induced choroidal neovascularization (CNV) model), where the contralateral eye served as the control. After administration of therapeutics, vasculature was monitored for 14 days to evaluate leakiness. Rats were treated with either a low or high concentration of anti-angiogenic peptide hydrogel (0.02 wt% 8 rats, 0.2 wt% 6 rats), or a pro-angiogenic peptide hydrogel (1.0 wt% 7 rats). As controls, six rats were treated with commercially available Aflibercept and six with sucrose solution (vehicle control). Post lasering, efficacy was determined over 14 days via fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Before and after treatment, the average areas of vascular leak per lesion were evaluated as well as the overall vessel leakiness. Unexpectedly, treatment with pro-angiogenic peptide hydrogel showed significant, immediate improvement in reducing vascular leak; in the short term, the pro-angiogenic peptide performed better than anti-angiogenic peptide hydrogel and was comparable to Aflibercept. After 14 days, both the pro-angiogenic and anti-angiogenic peptide hydrogels show a trend of improvement, comparable to Aflibercept. Based on our results, both anti-angiogenic and pro-angiogenic peptide hydrogels may prove good therapeutics in the future to treat wet AMD over a longer-term treatment period. |
| Author | Sanyal, Sreya Shi, Siyu Kaja, Simon Acevedo-Jake, Amanda Schur, Rebecca Siddiqui, Zain Yuan, Alex Kumar, Vivek A. |
| AuthorAffiliation | 3 Department of Biology, New Jersey Institute of Technology, Newark, NJ 07102, USA; ss3742@njit.edu 4 Cole Eye Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA; SCHURR@ccf.org (R.S.); yuana@ccf.org (A.Y.) 5 Research & Development Division, Experimentica Ltd., 70211 Kuopio, Finland; kaja@experimentica.com 8 Department of Restorative Dentistry, Rutgers School of Dental Medicine, Newark, NJ 07102, USA 6 Department of Ophthalmology, Loyola University Chicago, Maywood, IL 60153, USA 7 Department of Chemical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA 1 Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA; mauvocado@gmail.com (A.A.-J.); zs67@njit.edu (Z.S.) 2 Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA; siyushi@stanford.edu |
| AuthorAffiliation_xml | – name: 6 Department of Ophthalmology, Loyola University Chicago, Maywood, IL 60153, USA – name: 4 Cole Eye Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA; SCHURR@ccf.org (R.S.); yuana@ccf.org (A.Y.) – name: 8 Department of Restorative Dentistry, Rutgers School of Dental Medicine, Newark, NJ 07102, USA – name: 1 Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA; mauvocado@gmail.com (A.A.-J.); zs67@njit.edu (Z.S.) – name: 5 Research & Development Division, Experimentica Ltd., 70211 Kuopio, Finland; kaja@experimentica.com – name: 3 Department of Biology, New Jersey Institute of Technology, Newark, NJ 07102, USA; ss3742@njit.edu – name: 7 Department of Chemical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA – name: 2 Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA; siyushi@stanford.edu |
| Author_xml | – sequence: 1 givenname: Amanda surname: Acevedo-Jake fullname: Acevedo-Jake, Amanda – sequence: 2 givenname: Siyu surname: Shi fullname: Shi, Siyu – sequence: 3 givenname: Zain surname: Siddiqui fullname: Siddiqui, Zain – sequence: 4 givenname: Sreya surname: Sanyal fullname: Sanyal, Sreya – sequence: 5 givenname: Rebecca surname: Schur fullname: Schur, Rebecca – sequence: 6 givenname: Simon surname: Kaja fullname: Kaja, Simon – sequence: 7 givenname: Alex surname: Yuan fullname: Yuan, Alex – sequence: 8 givenname: Vivek A. orcidid: 0000-0001-7536-9281 surname: Kumar fullname: Kumar, Vivek A. |
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| CitedBy_id | crossref_primary_10_1016_j_xcrm_2023_101353 crossref_primary_10_1016_j_ijpharm_2024_124258 crossref_primary_10_3390_electronics11152294 crossref_primary_10_1021_acs_biomac_3c01345 crossref_primary_10_1021_acsami_3c15660 crossref_primary_10_1021_acsbiomaterials_3c00672 crossref_primary_10_29328_journal_abse_1001024 |
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| Keywords | tissue regeneration anti-angiogenic wet age-related macular degeneration hydrogel pro-angiogenic biomaterials multi-functional scaffolds |
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| SubjectTerms | Age Age related diseases Amino acids Angiogenesis Angiography anti-angiogenic Antiangiogenics Biocompatibility Bioengineering biomaterials Biomedical materials Blood vessels Design Diabetic retinopathy Eye diseases Fluorescein hydrogel Hydrogels Lasers Macular degeneration Medical imaging Peptides Permeability pro-angiogenic Sucrose Tissue engineering tissue regeneration Tomography Vascularization wet age-related macular degeneration |
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| Title | Preclinical Efficacy of Pro- and Anti-Angiogenic Peptide Hydrogels to Treat Age-Related Macular Degeneration |
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