Conditional knockout of Fbn1 in mouse non-pigmented ciliary epithelium led to reduced zonular tensile strength, zonular rupture, and ectopia lentis by 3 months.
Does targeted deletion of Fbn1 in mouse NPCE cause ocular phenotypes associated with Marfan syndrome?
Conditional knockout of Fbn1 in the mouse non-pigmented ciliary epithelium successfully models key ocular features of Marfan syndrome, providing insights into fibrillin-1's role in eye disease.
ABSTRACT Fibrillin is an evolutionarily ancient protein that lends elasticity and resiliency to a variety of tissues. In humans, mutations in fibrillin-1 cause Marfan and related syndromes, conditions in which the eye is often severely affected. To gain insights into the ocular sequelae of Marfan syndrome, we targeted Fbn1 in mouse lens or non-pigmented ciliary epithelium (NPCE). Conditional knockout of Fbn1 in NPCE, but not lens, profoundly affected the ciliary zonule, the system of fibrillin-rich fibers that centers the lens in the eye. The tensile strength of the fibrillin-depleted zonule was reduced substantially, due to a shift toward production of smaller caliber fibers. By 3 months, zonular fibers invariably ruptured and mice developed ectopia lentis, a hallmark of Marfan syndrome. At later stages, untethered lenses lost their polarity and developed cataracts, and the length and volume of mutant eyes increased. This model thus captures key aspects of Marfan-related syndromes, providing insights into the role of fibrillin-1 in eye development and disease.
Jones et al. (Tue,) conducted a other in Marfan syndrome ocular phenotypes. Conditional knockout of Fbn1 in NPCE or lens was evaluated on Development of ectopia lentis and other ocular phenotypes. Conditional knockout of Fbn1 in mouse non-pigmented ciliary epithelium led to reduced zonular tensile strength, zonular rupture, and ectopia lentis by 3 months.