Figure 2

Severe iris disease in double-congenic B6. Tyrp1 ^b Gpnmb ^R150X mice. Cohorts of B6.Tyrp1 ^isa Gpnmb ^R150Xmice were aged and analyzed by slit-lamp examination; representative eyes of indicated ages are shown. Each row contains three images of the same eye. The left column shows broad-beam illumination. The middle column shows transillumination defects. The right column shows the relative dimensions of the anterior chamber. The degree of pigment dispersion and iris atrophy is remarkably similar in both timing and severity to that of D2 mice (see reference [19] for comparable image of D2 eyes). (A to C) Until 5 months, B6.Tyrp1 ^b Gpnmb ^R150Xeyes were indistinguishable from wild-type, with a complex iris morphology, no transillumination, and anterior chambers of normal dimension with a closely juxtaposed cornea and iris. (D to F) By 6 months, all B6.Tyrp1 ^b Gpnmb ^R150Xeyes exhibit a clear phenotype characterized by slight swelling of peripupillary tissue. This timing and phenotype closely resembles the initial stages of the D2 iris disease. (G to I) In 9-month-old eyes, the peripupillary region becomes notably atrophic, transillumination is obvious, and dispersed pigment is present on both the lens and cornea. Beyond this age, a steadily worsening course ensues, which at (J to L) 12 months, (M to O) 14 months, and (P to R) 18 months is characterized by increasing degrees of iris atrophy that include full-thickness iris holes, profound transillumination, pigment dispersion and frequent pigment accumulation on the lens and cornea, and changes to the dimensions of the anterior chamber. No sex-specific differences were evident in these phenotypes. This synopsis of disease progression involved >146 eyes aged 2–20+ months, with each of the cohorts described above involving groups of at least 14 eyes.