Abstract
Retinal phenotypes of the PPCD1 mouse, a mouse model of posterior polymorphous corneal dystrophy, have been characterized. PPCD1 mice on the DBA/2J background (D2.Ppcd1) have previously been reported to develop an enlarged anterior chamber due to epithelialization and proliferation of the corneal endothelium and subsequent blockage of the iridocorneal angle. Results presented here show that D2.Ppcd1 mice develop increased intraocular pressure (IOP), with measurements at three months of age revealing significant increases in IOP. Significant retinal ganglion cell layer cell loss is observed at five months of age. D2.Ppcd1 animals also exhibit marked degeneration of the outer nuclear layer in association with hyperplasia of the retinal pigment epithelium. Evidence of retinal detachment is present as early as three weeks of age. By 3.5 months of age, focal areas of outer nuclear layer loss are observed. Although the GpnmbR150X mutation leads to increased IOP and glaucoma in DBA/2J mice, development of anterior segment and retinal defects in D2.Ppcd1 animals does not depend upon presence of the GpnmbR150X mutation.
Highlights
Human posterior polymorphous corneal dystrophy (PPCD, OMIM #122000) is an autosomal dominant disorder characterized by metaplasia of the corneal endothelium [1,2,3,4]
We demonstrate that D2.Ppcd1 animals develop increased intraocular pressure and loss of retinal ganglion cell layer (RGCL) cells, as well as abnormalities of the retinal pigment epithelium leading to outer nuclear layer (ONL) degeneration
The anterior chamber is clearly enlarged at postnatal day 8, suggesting that increased intraocular pressure develops at an early age in D2.Ppcd1 animals
Summary
Human posterior polymorphous corneal dystrophy (PPCD, OMIM #122000) is an autosomal dominant disorder characterized by metaplasia of the corneal endothelium [1,2,3,4]. PPCD and autosomal dominant congenital hereditary endothelial corneal dystrophy, as well as the sporadic disorder, iridocorneal endothelial syndrome (ICE), exhibit overlapping clinical and pathological features, including ultrastructural changes and abnormal patterns of cytokeratin expression consistent with epithelialization of the corneal endothelium. Steepening of the cornea has been reported, suggesting a link to keratoconus [6], as well as a single case of colloid drusen formation [7]. Human PPCD has been linked to three chromosomal loci, PPCD1 (OVOL2) on Chromosome 20 [5, 8,9,10], PPCD2 (COL8A2) on Chromosome
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