ID1 and ID3 are Negative Regulators of TGFbeta2-Induced Ocular Hypertension and Compromised Aqueous Humor Outflow Facility in Mice

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dc.creatorMody, Avani A.
dc.creatorMillar, J. Cameron
dc.creatorClark, Abbot F.
dc.creator.orcid0000-0003-3594-6560 (Clark, Abbot F.)
dc.date.accessioned2022-09-13T16:34:17Z
dc.date.available2022-09-13T16:34:17Z
dc.date.issued2021-05-03
dc.description.abstractPurpose: In POAG, elevated IOP remains the major risk factor in irreversible vision loss. Increased TGFbeta2 expression in POAG aqueous humor and in the trabecular meshwork (TM) amplifies extracellular matrix (ECM) deposition and reduces ECM turnover in the TM, leading to a decreased aqueous humor (AH) outflow facility and increased IOP. Inhibitor of DNA binding proteins (ID1 and ID3) inhibit TGFbeta2-induced fibronectin and PAI-1 production in TM cells. We examined the effects of ID1 and ID3 gene expression on TGFbeta2-induced ocular hypertension and decreased AH outflow facility in living mouse eyes. Methods: IOP and AH outflow facility changes were determined using a mouse model of Ad5-hTGFbeta2C226S/C288S-induced ocular hypertension. The physiological function of ID1 and ID3 genes were evaluated using Ad5 viral vectors to enhance or knockdown ID1/ID3 gene expression in the TM of BALB/cJ mice. IOP was measured in conscious mice using a Tonolab impact tonometer. AH outflow facilities were determined by constant flow infusion in live mice. Results: Over-expressing ID1 and ID3 significantly blocked TGFbeta2-induced ocular hypertension (P < 0.0001). Although AH outflow facility was significantly decreased in TGFbeta2-transduced eyes (P < 0.04), normal outflow facility was preserved in eyes injected concurrently with ID1 or ID3 along with TGFbeta2. Knockdown of ID1 or ID3 expression exacerbated TGFbeta2-induced ocular hypertension. Conclusions: Increased expression of ID1 and ID3 suppressed both TGFbeta2-elevated IOP and decreased AH outflow facility. ID1 and/or ID3 proteins thus may show promise as future candidates as IOP-lowering targets in POAG.
dc.description.sponsorshipPartially supported by Sigma Xi grant G20141015669897.
dc.identifier.citationMody, A. A., Millar, J. C., & Clark, A. F. (2021). ID1 and ID3 are Negative Regulators of TGFβ2-Induced Ocular Hypertension and Compromised Aqueous Humor Outflow Facility in Mice. Investigative ophthalmology & visual science, 62(6), 3. https://doi.org/10.1167/iovs.62.6.3
dc.identifier.issn1552-5783
dc.identifier.issue6
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31728
dc.identifier.volume62
dc.publisherARVO Journals
dc.relation.urihttps://doi.org/10.1167/iovs.62.6.3
dc.rights.holderCopyright 2021 The Authors
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceInvestigative Ophthalmology & Visual Science
dc.subject.meshAdenoviridae / genetics
dc.subject.meshAnimals
dc.subject.meshAqueous Humor / physiology
dc.subject.meshFemale
dc.subject.meshGene Knockdown Techniques
dc.subject.meshGenetic Vectors
dc.subject.meshInhibitor of Differentiation Protein 1 / physiology
dc.subject.meshInhibitor of Differentiation Proteins / physiology
dc.subject.meshIntraocular Pressure / drug effects
dc.subject.meshIntravitreal Injections
dc.subject.meshMice
dc.subject.meshMice, Inbred BALB C
dc.subject.meshOcular Hypertension / chemically induced
dc.subject.meshOcular Hypertension / metabolism
dc.subject.meshTonometry, Ocular
dc.subject.meshTrabecular Meshwork / drug effects
dc.subject.meshTrabecular Meshwork / metabolism
dc.subject.meshTransforming Growth Factor beta2 / pharmacology
dc.titleID1 and ID3 are Negative Regulators of TGFbeta2-Induced Ocular Hypertension and Compromised Aqueous Humor Outflow Facility in Mice
dc.typeArticle
dc.type.materialtext

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