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Abstract #60528 Published in IGR 16-4
A Novel Mgp-Cre Knock-in Mouse Reveals an Anti-calcification/anti-stiffness Candidate Gene in the Trabecular Meshwork and Scleral Peripapillary Region
Borras T; Smith MH; Buie LKInvestigative Ophthalmology and Visual Science 2015; 56: 2203-2214
PURPOSE: Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp Knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Since tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues utilize Mgp's function using Knock-in mice. METHODS: An Mgp-Cre Knock-in mouse, containing Mgp DNA plus an IRES-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ Knock-in) and controls, 1-8 months were assayed for β-gal enzyme histochemistry. RESULTS: As expected, Mgp-lacZ Knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began mid-sclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body and retina were negative. All mice exhibited similar staining patterns. All controls were negative. CONCLUSIONS: MGP's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. MGP's anti-calcification/anti-stiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma.
Ophthalmology, University of North Carolina, 4109C Neuroscience Research Bld., Campus Box 7041, Chapel Hill, North Carolina, 27599, United States tborras@med.unc.edu.
Full articleClassification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
2.3 Sclera (Part of: 2 Anatomical structures in glaucoma)
2.14 Optic disc (Part of: 2 Anatomical structures in glaucoma)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
