Lama1 mutations lead to vitreoretinal blood vessel formation, persistence of fetal vasculature, and epiretinal membrane formation in mice

Although astrocytes and blood vessels initially migrate into Lama1 mutant retinas, both traverse the peripapillary ILM into the vitreous by P3. Once in the vitreous, blood vessels anastomose with vessels of the vasa hyaloidea propria, part of the FVV, and eventually re-enter the retina where they dive to form the inner and outer retinal capillary networks. Astrocytes continue proliferating within the vitreous to form a dense mesh that resembles epiretinal membranes associated with persistent fetal vasculature and proliferative vitreoretinopathy.Lama1 and a fully intact ILM are required for normal retinal vascular development. Mutations in Lama1 allow developing retinal vessels to enter the vitreous where they anastomose with vessels of the hyaloid system which persist and expand. Together, these vessels branch into the retina to form fairly normal inner retinal vascular capillary plexi. The Lama1 mutants described in this report are potential models for studying the human conditions persistent fetal vasculature and proliferative vitreoretinopathy.The retinal vasculature, which nourishes the inner retina, consists of three plexi: the superficial in the nerve fiber layer, the intermediate in the inner plexiform layer, and the deep in the outer plexiform layer. The photoreceptors in the outer retina are maintained by the choroidal vessels. Retinal vessels develop in man during fetal development [1] but in mice during the first 3 post-natal weeks [2]. Prior to the formation of retinal vessels, the lens and developing inner retina are nourished by the hyaloid vasculature. This three component vasculature (hyaloid artery, vasa hyaloidea propria, and tunica vasculosa lentis) lies in the vitreous, a gel-like structure separating the retina and the lens. The hyaloid vessels regress as retinal vessels form and are gone in humans by birth and by three weeks in the mouse. The portion of the hyaloid vasculature closest to the retina is the vasa hyaloidea propria (VHP) which is a