Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization
Purpose: To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD).Methods: In the first of two studies, Brown Norway rats underwent laser-induced CNV and were assigned to one...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.780841/full |
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| author | Juan Carlos Martinez-Camarillo Juan Carlos Martinez-Camarillo Christine K. Spee Gloria Paulina Trujillo-Sanchez Gloria Paulina Trujillo-Sanchez Anthony Rodriguez David R. Hinton David R. Hinton Alessandra Giarola Victor Pikov Arun Sridhar Mark S. Humayun Mark S. Humayun Andrew C. Weitz Andrew C. Weitz |
| author_facet | Juan Carlos Martinez-Camarillo Juan Carlos Martinez-Camarillo Christine K. Spee Gloria Paulina Trujillo-Sanchez Gloria Paulina Trujillo-Sanchez Anthony Rodriguez David R. Hinton David R. Hinton Alessandra Giarola Victor Pikov Arun Sridhar Mark S. Humayun Mark S. Humayun Andrew C. Weitz Andrew C. Weitz |
| author_sort | Juan Carlos Martinez-Camarillo |
| collection | DOAJ |
| description | Purpose: To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD).Methods: In the first of two studies, Brown Norway rats underwent laser-induced CNV and were assigned to one of the following groups: daily eye drops of artificial tears (n = 10; control group); daily eye drops of the β-adrenoreceptor agonist isoproterenol (n = 10); daily eye drops of the β-adrenoreceptor antagonist propranolol (n = 10); sympathetic internal carotid nerve (ICN) transection 6 weeks prior to laser-induced CNV (n = 10). In the second study, rats underwent laser-induced CNV followed by ICN transection at different time points: immediately after the laser injury (n = 6), 7 days after the laser injury (n = 6), and sham surgery 7 days after the laser injury (n = 6; control group). All animals were euthanized 14 days after laser application. CNV development was quantified with fluorescein angiography and optical coherence tomography (in vivo), as well as lesion volume analysis using 3D confocal reconstruction (postmortem). Angiogenic growth factor protein levels in the choroid were measured with ELISA.Results: In the first study, blocking ocular sympathetic activity through pharmacological or surgical manipulation led to a 75% or 70% reduction in CNV lesion volume versus the control group, respectively (P < 0.001). Stimulating ocular sympathetic activity with isoproterenol also led to a reduction in lesion volume, but only by 27% versus controls (P < 0.05). VEGF protein levels in the choroid were elevated in the three treatment groups (P < 0.01). In the second study, fluorescein angiography and CNV lesion volume analysis indicated that surgically removing the ocular sympathetic supply inhibited progression of laser-induced CNV, regardless of whether ICN transection was performed on the same day or 7 days after the laser injury.Conclusion: Surgical and pharmacological block of ocular sympathetic activity can inhibit progression of CNV in a rat model. Therefore, electrical block of ICN activity could be a potential bioelectronic medicine strategy for treating wet AMD. |
| first_indexed | 2024-12-20T06:26:17Z |
| format | Article |
| id | doaj.art-bf683afde8274573958abea9554effc2 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-20T06:26:17Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-bf683afde8274573958abea9554effc22022-12-21T19:50:17ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-01-011510.3389/fnins.2021.780841780841Blocking Ocular Sympathetic Activity Inhibits Choroidal NeovascularizationJuan Carlos Martinez-Camarillo0Juan Carlos Martinez-Camarillo1Christine K. Spee2Gloria Paulina Trujillo-Sanchez3Gloria Paulina Trujillo-Sanchez4Anthony Rodriguez5David R. Hinton6David R. Hinton7Alessandra Giarola8Victor Pikov9Arun Sridhar10Mark S. Humayun11Mark S. Humayun12Andrew C. Weitz13Andrew C. Weitz14USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesUSC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, United StatesDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesUSC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesUSC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, United StatesDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesUSC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, United StatesDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesGalvani Bioelectronics, Stevenage, United KingdomGalvani Bioelectronics, Stevenage, United KingdomGalvani Bioelectronics, Stevenage, United KingdomUSC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesUSC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, United StatesUSC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesUSC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, United StatesPurpose: To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD).Methods: In the first of two studies, Brown Norway rats underwent laser-induced CNV and were assigned to one of the following groups: daily eye drops of artificial tears (n = 10; control group); daily eye drops of the β-adrenoreceptor agonist isoproterenol (n = 10); daily eye drops of the β-adrenoreceptor antagonist propranolol (n = 10); sympathetic internal carotid nerve (ICN) transection 6 weeks prior to laser-induced CNV (n = 10). In the second study, rats underwent laser-induced CNV followed by ICN transection at different time points: immediately after the laser injury (n = 6), 7 days after the laser injury (n = 6), and sham surgery 7 days after the laser injury (n = 6; control group). All animals were euthanized 14 days after laser application. CNV development was quantified with fluorescein angiography and optical coherence tomography (in vivo), as well as lesion volume analysis using 3D confocal reconstruction (postmortem). Angiogenic growth factor protein levels in the choroid were measured with ELISA.Results: In the first study, blocking ocular sympathetic activity through pharmacological or surgical manipulation led to a 75% or 70% reduction in CNV lesion volume versus the control group, respectively (P < 0.001). Stimulating ocular sympathetic activity with isoproterenol also led to a reduction in lesion volume, but only by 27% versus controls (P < 0.05). VEGF protein levels in the choroid were elevated in the three treatment groups (P < 0.01). In the second study, fluorescein angiography and CNV lesion volume analysis indicated that surgically removing the ocular sympathetic supply inhibited progression of laser-induced CNV, regardless of whether ICN transection was performed on the same day or 7 days after the laser injury.Conclusion: Surgical and pharmacological block of ocular sympathetic activity can inhibit progression of CNV in a rat model. Therefore, electrical block of ICN activity could be a potential bioelectronic medicine strategy for treating wet AMD.https://www.frontiersin.org/articles/10.3389/fnins.2021.780841/fullwet AMDinternal carotid nervechoroidal neovascularizationocular sympathetic activitylaser-induced CNVβ-adrenoreceptor modulation |
| spellingShingle | Juan Carlos Martinez-Camarillo Juan Carlos Martinez-Camarillo Christine K. Spee Gloria Paulina Trujillo-Sanchez Gloria Paulina Trujillo-Sanchez Anthony Rodriguez David R. Hinton David R. Hinton Alessandra Giarola Victor Pikov Arun Sridhar Mark S. Humayun Mark S. Humayun Andrew C. Weitz Andrew C. Weitz Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization Frontiers in Neuroscience wet AMD internal carotid nerve choroidal neovascularization ocular sympathetic activity laser-induced CNV β-adrenoreceptor modulation |
| title | Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization |
| title_full | Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization |
| title_fullStr | Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization |
| title_full_unstemmed | Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization |
| title_short | Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization |
| title_sort | blocking ocular sympathetic activity inhibits choroidal neovascularization |
| topic | wet AMD internal carotid nerve choroidal neovascularization ocular sympathetic activity laser-induced CNV β-adrenoreceptor modulation |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.780841/full |
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