Investigating pigment dispersion syndrome using an inducible mouse model

Abstract

Purpose: Pigment dispersion syndrome (PDS) is an important glaucoma risk factor. PDS can lead to elevated intraocular pressure (IOP). Many, but not all, eyes afflicted with PDS develop IOP elevation. The biological events shaping how an eye responds to PDS are currently not well understood. The purpose of these experiments is to create an inducible mouse model of pigment dispersion to study the progression of PDS to elevated IOP.

Methods: Cohorts (n=5 mice each) of C57BL/6J (B6) mice homozygous for the Tyr^c-2J allele (B6.Tyr^c-2J/J) received intraocular infusion of donor iris preparations made from dissected irides of B6, B6.Tyr^c-2J/J mice, or vehicle only control. Ocular phenotypes of recipient mice were collected pre- (baseline) and post-infusion (response) using slit lamp and gonioscopic imaging, rebound tonometry to measure IOP, and histology.

Results: Infusion of recipient eyes with donor iris preparations results in anterior chamber phenotypes resembling PDS without overt signs of inflammation. Slit lamp photography illustrates that iridial melanin localizes to the tissues at the iridocorneal angle. Histological analyses show a sustained presence of pigment in macrophages and throughout the trabecular meshwork. Recipient eyes infused with iris preparations from Tyr^+/+ donors exhibit significant IOP elevation (p<0.02,) whereas preparations from Tyr^c-2J do not.

Conclusions: These results demonstrate that ocular phenotypes of PDS can be recapitulated in this inducible mouse model. The presence of melanin in the infused iris preparations is critical for IOP elevation. In ongoing work, this inducible model will be used to study biological responses in the eye that contribute or protect from IOP elevation.

Keywords: 735 trabecular meshwork • 571 iris • 536 gene modifiers