Figure 2

D2- Gpnmb⁺ bone marrow suppresses iris depigmentation and anterior chamber enlargement. Representative eyes of the indicated strains and ages are shown. The three left most columns show broad beam illumination to assay for the presence of dispersed pigment within the anterior chamber and iris stromal morphology. The fourth column shows a transilluminating view assaying the degree of iris depigmentation, detectable as red areas within the image where reflected light is passing through the iris. The fifth column show anterior chamber dimensions. Each row represents a different genetic context of either unmanipulated mice (rows 1 & 2) or bone marrow chimeras (rows 3 & 4). (A to E) Unmanipulated D2-Gpnmb⁺ mice (WT) exhibit a characteristic iris stromal atrophy phenotype caused by the Tyrp1^bmutation that is largely devoid of significant pigment dispersion at all examined ages (1–15 mo). Eyes of D2-Gpnmb⁺ mice do not develop significant transillumination and maintain a normal anterior chamber depth with very little space between the iris and cornea. (F to J) Unmanipulated D2 mice (homozygous for the Gpnmb^{R 150X}mutation) develop a severe pigment dispersing iris disease. At 5–6 mos, the initial stages of iris disease are apparent by a slight peripupillary thickening and subtle changes to the morphology of the iris stroma (note slightly roughened appearance). Subsequently, dispersed pigment becomes aberrantly deposited on a variety of structures including the surface of the iris, lens, and cornea. Dispersed pigment is also deposited in the aqueous humor drainage structures, leading to increased IOP and enlargement of the anterior chamber (space indicated by arrows in J). (K to O) D2-Gpnmb⁺marrow transferred to D2.Gpnmb^{R 150X}recipients (WT → R150X) exhibit a pronounced suppression of the typical D2 disease progression. Most notably, the extent of iris degeneration is lessened (compare the peripupillary region of M vs H, and degree of transillumination defects in N vs I) and the anterior chamber does not become enlarged (compare O vs J). (P to T) D2 marrow transferred to D2-Gpnmb⁺ recipients (R150X → WT) exhibit no alterations in ocular phenotype compared to unmanipulated D2-Gpnmb⁺ mice.