{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:50:21Z","timestamp":1758635421387,"version":"3.41.2"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> 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 (<jats:italic>n<\/jats:italic> = 10; control group); daily eye drops of the \u03b2-adrenoreceptor agonist isoproterenol (<jats:italic>n<\/jats:italic> = 10); daily eye drops of the \u03b2-adrenoreceptor antagonist propranolol (<jats:italic>n<\/jats:italic> = 10); sympathetic internal carotid nerve (ICN) transection 6 weeks prior to laser-induced CNV (<jats:italic>n<\/jats:italic> = 10). In the second study, rats underwent laser-induced CNV followed by ICN transection at different time points: immediately after the laser injury (<jats:italic>n<\/jats:italic> = 6), 7 days after the laser injury (<jats:italic>n<\/jats:italic> = 6), and sham surgery 7 days after the laser injury (<jats:italic>n<\/jats:italic> = 6; control group). All animals were euthanized 14 days after laser application. CNV development was quantified with fluorescein angiography and optical coherence tomography (<jats:italic>in vivo<\/jats:italic>), as well as lesion volume analysis using 3D confocal reconstruction (postmortem). Angiogenic growth factor protein levels in the choroid were measured with ELISA.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> 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 (<jats:italic>P<\/jats:italic> &amp;lt; 0.001). Stimulating ocular sympathetic activity with isoproterenol also led to a reduction in lesion volume, but only by 27% versus controls (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). VEGF protein levels in the choroid were elevated in the three treatment groups (<jats:italic>P<\/jats:italic> &amp;lt; 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.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> 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.<\/jats:p>","DOI":"10.3389\/fnins.2021.780841","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T06:10:23Z","timestamp":1641795023000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization"],"prefix":"10.3389","volume":"15","author":[{"given":"Juan Carlos","family":"Martinez-Camarillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine K.","family":"Spee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria Paulina","family":"Trujillo-Sanchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Hinton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Giarola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Pikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun","family":"Sridhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Humayun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C.","family":"Weitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/nrd4351","article-title":"Bioelectronic medicines: a research roadmap.","volume":"13","author":"Birmingham","year":"2014","journal-title":"Nat. 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