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Abstract #86634 Published in IGR 21-2

Targeted deletion of Cyp1b1 in pericytes results in attenuation of retinal neovascularization and trabecular meshwork dysgenesis

Falero-Perez J; Larsen MC; Teixeira LBC; Zhang HF; Lindner V; Sorenson CM; Jefcoate CR; Sheibani N
Trends in developmental biology 2019; 12: 1-12

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Mutations in cytochrome P450 1B1 (CYP1B1) gene are reported in patients with primary congenital glaucoma. -deficient (-/-) mice show dysgenesis of the trabecular meshwork (TM) tissue and attenuation of retinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Although retinal vascular cells, including endothelial cells (EC), pericytes (PC), astrocytes (AC), and TM endothelial cells express CYP1B1, the cell autonomous contribution of CYP1B1 to attenuation of retinal neovascularization and TM tissue dysgenesis remains unknown. Here we determined the impact lack of CYP1B1 expression in EC, PC or AC has on retinal neovascularization and TM tissue integrity. We generated -transgenic mice with vascular cell-specific targeted Cre-deletion in EC (), in PC () and in AC (). Pathologic retinal neovascularization during OIR was evaluated by collagen IV staining of retinal wholemounts. Structural morphology of TM tissue was examined by transmission electron microscopy (TEM). The assessment of retinal neovascularization indicated a significant decrease in retinal neovascular tufts only in mice compared with control mice. TEM evaluation demonstrated mice also exhibited a defect in TM tissue morphology and integrity similar to that reported in -/- mice. Thus, Cyp1b1 expression in PC plays a significant role in retinal neovascularization and the integrity of TM tissue.

Departments of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

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Classification:

2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
3.9 Pathophysiology (Part of: 3 Laboratory methods)

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