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Seyyedhassan Paylakhi, Cassandre LabelleDumais, Michael Sellarole, Saidas Nair; Prss56 Mutant Mouse: a Model for Nanophthalmos-Related Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5381.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in human PRSS56 cause nanophthalmos/posterior microphthalmia. Nanophthalmic eyes exhibit severely reduced ocular axial length and high hyperopia. Moreover, these eyes are susceptible to developing uveal effusion characterized by suprachroidal fluid accumulation due to trans-scleral drainage defects. Leakage of the accumulated fluid into the subretinal space induces retinal detachment. Mice with a mutation in Prss56 recapitulate features of human nanophthalmos (hyperopia and reduced ocular axial length). Here, we assess if Prss56 mutant mice are susceptible to developing retinal detachment. Furthermore, we employ a genetic strategy to rescue the ocular size reduction in Prss56 mutant mice and utilize this new model to study the link between ocular size and retinal detachment.
1) To detect retinal detachment, we examined the retina of Prss56 mutant and control littermates between 2 and 12 months of age, using funduscopy, optical coherence tomography (OCT), fluorescein angiography and histology. 2) We bred Egr1 knockout mouse, a previously reported model for ocular axial elongation/myopia, to a Prss56 mutant mouse to study the genetic interaction between Egr1 and Prss56 for ocular size regulation and retinal detachment. Ocular dimensions and refraction were measured using a digital vernier caliper and mouse photo-refractor respectively.
1) Fundus examination revealed the presence of retinal lesions in Prss56 mutant eyes starting at 5 months of age. OCT examination suggests that these lesions correspond to areas of retinal detachment. Histological analysis confirmed the presence of focal retinal detachment in Prss56 mutant eyes. The retinal detachment exacerbates with age. The retinal detachment is accompanied by vascular leakage and gliosis. 2) Inactivation of Egr1 partially rescues the Prss56 mutant mediated reduction in ocular axial length and corrects hyperopia. In addition, inactivation of Egr1 rescues retinal detachment observed in Prss56 mutant eyes.
In addition to ocular size reduction and hyperopia, Prss56 mutant mice develop progressive, age-related retinal detachment. Importantly, inactivation of Egr1 rescues the retinal detachment observed in Prss56 mutant mice, likely through its effect on partially reversing the reduction in ocular size. Thus, Prss56 mutant mice constitute a valuable model to study the role of ocular size and related defects in retinal detachment.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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