Retina-derived signals regulating development of the vitreous hyaloid vasculature

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DESCRIPTION (provided by applicant): The hyaloid vascular system (HVS) is a transient vascular network that nourishes the immature lens and retina before formation of the retinal vasculature. Defects in HVS development can lead to serious congenital eye diseases, including persistent hyperplastic primary vitreous (PHPV). PHPV is characterized by the presence of fibrovascular retrolental mass tissue in the vitreous, microphthalmia and leukokoria, and is associated with cataract, retinal folding and detachment. A better understanding of how development of the HVS is governed should provide insights into the pathogenesis of such congenital eye diseases. We found that selective knockout of the gene for the Wnt receptor Frizzled-5 (Fzd5) in the developing mouse retina and optic stalk causes early hyperplasia of the vitreous hyaloid vasculature and persistence at later stages, resembling the human disease PHPV. Since Fzd5 was selectively disrupted in the retina and not the vasculature itself, the effect is non-autonomous. We hypothesize that loss of Fzd5 in the retina alters signaling between the retina and components of the developing HVS, resulting in hyperplasia and subsequent persistence of this tissue. The goal of this proposal is to identify candidate retina-derived factors and reveal the mechanisms through which the development of the HVS may be regulated by signals from retina. This may lead to novel strategies to treat congenital eye disease such as PHPV. PUBLIC HEALTH RELEVANCE: The hyaloid vascular system (HVS) is a transient arterial network that nourishes the immature lens as well as the retinal neuroepithelium before formation of the retinal vasculature. The mechanisms governing the normal development of the HVS have not been well defined. Defects in HVS development can lead to serious congenital eye diseases, including persistent hyperplastic primary vitreous (PHPV). A better understanding of this process may lead to strategies to potentially prevent or treat congenital eye diseases such as PHPV.