title: Elevation of intraocular pressure in rodents using viral vectors targeting the trabecular meshwork.
abstract: Rodents are increasingly being used as glaucoma models to study ocular hypertension, optic neuropathy, and retinopathy. A number of different techniques are used to elevate intraocular pressure in rodent eyes by artificially obstructing the aqueous outflow pathway. Another successful technique to induce ocular hypertension is to transduce the trabecular meshwork of rodent eyes with viral vectors expressing glaucoma associated transgenes to provide more relevant models of glaucomatous damage to the trabecular meshwork. This technique has been used to validate newly discovered glaucoma pathogenesis pathways as well as to develop rodent models of primary open angle glaucoma. Ocular hypertension has successfully been induced by adenovirus 5 mediated delivery of mutant MYOC, bioactivated TGFβ2, SFRP1, DKK1, GREM1, and CD44. Advantages of this approach are: selective tropism for the trabecular meshwork, the ability to use numerous mouse strains, and the relatively rapid onset of IOP elevation. Disadvantages include mild-to-moderate ocular inflammation induced by the Ad5 vector and sometimes transient transgene expression. Current efforts are focused at discovering less immunogenic viral vectors that have tropism for the trabecular meshwork and drive sufficient transgene expression to induce ocular hypertension. This viral vector approach allows rapid proof of concept studies to study glaucomatous damage to the trabecular meshwork without the expensive and time-consuming generation of transgenic mouse lines.
authors.affiliation: North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA; Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA; Department of Cell Biology & Immunology, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Iok-Hou
authors.initials: IH
authors.lastname: Pang
authors.affiliation: North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA; Department of Cell Biology & Immunology, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: J Cameron
authors.initials: JC
authors.lastname: Millar
authors.affiliation: North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA; Department of Cell Biology & Immunology, University of North Texas Health Science Center, Fort Worth, TX, USA. Electronic address: abe.clark@unthsc.edu.
authors.forename: Abbot F
authors.initials: AF
authors.lastname: Clark
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005822:Genetic Vectors; D005901:Glaucoma / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007429:Intraocular Pressure / Q000502:physiology*; D008822:Mice, Transgenic; D014129:Trabecular Meshwork / Q000378:metabolism* / Q000821:virology; D019076:Transgenes; D014780:Viruses / Q000235:genetics*
keywords: Animal models; Glaucoma; Viral vectors