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IOP is the steady-state result of the balance among AH secretion (AHs), circulation (AHc), and drainage (AHd). AHs are modeled as a given volumetric flow rate electrically corresponding to an input current source. AHc is modeled by the series of two linear hydraulic conductances (HCs) representing the posterior and anterior chambers. AHd is modeled by the parallel of three HCs: a linear HC for the conventional adaptive route (ConvAR), a nonlinear HC for the hydraulic component of the unconventional adaptive route (UncAR), and a nonlinear HC for the drug-dependent component of the UncAR. The proposed model is implemented in a computational virtual laboratory to study the value attained by the IOP under physiological and pathological conditions. Simulation results (i) confirm the conjecture that the UncAR acts as a relief valve under pathological conditions, (ii) indicate that the drug-dependent AR is the major opponent to IOP increase in the case of elevated trabecular meshwork resistance, and (iii) support the use of the model as a quantitative tool to complement in vivo studies and help design and optimize medications for ocular diseases.<\/jats:p>","DOI":"10.1063\/5.0151091","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T11:24:35Z","timestamp":1686137075000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["The role of conventional and unconventional adaptive routes in lowering of intraocular pressure: Theoretical model and simulation"],"prefix":"10.1063","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3239-9995","authenticated-orcid":false,"given":"Riccardo","family":"Sacco","sequence":"first","affiliation":[{"name":"Dipartimento di Matematica, Politecnico di Milano 1 , 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-3446","authenticated-orcid":false,"given":"Greta","family":"Chiaravalli","sequence":"additional","affiliation":[{"name":"Center for Nanoscience and Technology, Istituto Italiano di Tecnologia 2 , 20133 Milano, Italy"},{"name":"Dipartimento di Fisica, Politecnico di Milano 3 , 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9897-4676","authenticated-orcid":false,"given":"Gal","family":"Antman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Icahn School of Medicine at Mount Sinai 4 , New York, New York 10029, USA"},{"name":"Department of Ophthalmology, Rabin Medical Center 5 , Petah Tikva 4941492, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Guidoboni","sequence":"additional","affiliation":[{"name":"College of Engineering, University of Maine 6 , Orono, Maine 04469, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6956-905X","authenticated-orcid":false,"given":"Alice","family":"Verticchio","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Icahn School of Medicine at Mount Sinai 4 , New York, New York 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6260-1700","authenticated-orcid":false,"given":"Brent","family":"Siesky","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Icahn School of Medicine at Mount Sinai 4 , New York, New York 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8770-3726","authenticated-orcid":false,"given":"Alon","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Icahn School of Medicine at Mount Sinai 4 , New York, New York 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2023,6,7]]},"reference":[{"key":"2023121515470280000_c1","first-page":"3145","article-title":"Flow of aqueous humor in humans","volume":"32","year":"1991","journal-title":"Invest. 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