NDLI: Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2.

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Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2.

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Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Buie, Lakisha K. Smith, Matthew H. Karim, Md Zahidul Borrás, Teresa
Description	Country affiliation: United States Author Affiliation: Buie LK ( Department of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7041, USA.)
Abstract	PURPOSE: To determine whether inducing calcification in the trabecular meshwork results in elevated IOP in living rats. To use this property to create an elevated IOP animal model by gene transfer of bone morphogenetic protein 2 (BMP2). METHODS: Calcification was assessed by alizarin red staining in primary human trabecular meshwork (HTM) cells and alkaline phosphatase (ALP) activity in the angle tissue. Brown Norway (BN) and Wistar rats were intracamerally injected with Ad5BMP2 (OS) and control Ad5.CMV-Null (OD). IOPs were taken twice a week and expressed as mean integral pressures. Morphology was assessed on fixed, paraffin-embedded anterior segments. Retinal ganglion cells (RGCs) were quantified on retrograde and Brn-3a-labeled flat mounts using MetaMorph software. RESULTS: BMP2-treated cells displayed marked increase in calcification. Trabecular meshwork tissue showed moderate ALP activity at 13 days postinjection. Fifty-four of 55 BN and 15 of 19 Wistar rats displayed significantly elevated IOP. In a representative 29-day experiment, the integral IOP difference between treated and control eyes was 367.7 ± 83 mm Hg-days (P = 0.007). Morphological evaluation revealed a well-organized trabecular meshwork tissue, exhibiting denser matrix in the treated eyes. The Ad5BMP2-treated eye showed 34.4% ± 4.8% (P = 0.00002) loss of peripheral RGC over controls. CONCLUSIONS: Gene transfer of the calcification inducer BMP2 gene to the trabecular meshwork induces elevated IOP in living rats without altering the basic structure of the tissue. This strategy generates an elevated IOP model in rats that would be useful for evaluation of glaucoma drugs targeting the outflow pathway.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.13-11651
Journal	Investigative Opthalmology & Visual Science
Issue Number	8
Volume Number	54
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2013-08-13
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Bone Morphogenetic Protein 2 Genetics Gene Expression Regulation Gene Transfer Techniques Intraocular Pressure Physiology Ocular Hypertension Trabecular Meshwork Pathology Adolescent Animals Administration & Dosage Biosynthesis Calcinosis Metabolism Cells, Cultured Disease Models, Animal Immunohistochemistry Physiopathology Rats, Inbred Bn Rats, Wistar Real-time Polymerase Chain Reaction Drug Effects Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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