Anterior Segment Dysgenesis and Early-Onset Glaucoma in nee Mice with Mutation of Sh3pxd2b

PURPOSE. Mutations in SH3PXD2B cause Frank-Ter Haar syndrome, a rare condition characterized by congenital glaucoma, as well as craniofacial, skeletal, and cardiac anomalies. The nee strain of mice carries a spontaneously arising mutation in Sh3pxd2b. The purpose of this study was to test whether nee mice develop glaucoma. METHODS. Eyes of nee mutants and strain-matched controls were comparatively analyzed at multiple ages by slit lamp examination, intraocular pressure recording, and histologic analysis. Cross sections of the optic nerve were analyzed to confirm glaucomatous progression. RESULTS. Slit lamp examination showed that, from an early age, nee mice uniformly exhibited severe iridocorneal adhesions around the entire circumference of the eye. Presumably as a consequence of aqueous humor outflow blockage, they rapidly developed multiple indices of glaucoma. By 3 to 4 months of age, they exhibited high intraocular pressure (30.8 +/- 12.5 mm Hg; mean +/- SD), corneal opacity, and enlarged anterior chambers. Although histologic analyses at P17 did not reveal any indices of damage, similar analysis at 3 to 4 months of age revealed a course of progressive retinal ganglion cell loss, optic nerve head excavation, and axon loss. CONCLUSIONS. Eyes of nee mice exhibit anterior segment dysgenesis and early-onset glaucoma. Because SH3PXD2B is predicted to be a podosome adaptor protein, these findings implicate podosomes in normal development of the iridocorneal angle and the genes influencing podosomes as candidates in glaucoma. Because of the early-onset, high-penetrance glaucoma, nee mice offer many potential advantages as a new mouse model of the disease. (Invest Ophthalmol Vis Sci. 2011;52:2679-2688) DOI:10.1167/iovs.10-5993