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Youwen Zhang, James Brett Stanton, Yong S Lee, Alan D Marmorstein, Lihua Marmortein; Deletion of EFEMP1 is protective against the development of basal deposits in mouse eyes.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2973.
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EFEMP1 (fibulin-3) is mutated in Malattia Leventinese/Doyne’s honeycomb retinal dystrophy (ML/DHRD), an autosomal dominantly inherited macular degenerative disease with strong similarities to age-related macular degeneration (AMD). Both ML/DHRD and AMD are characterized by basal deposits beneath the retinal pigment epithelium (RPE). While basal deposits develop in knock-in mice carrying the diseasing-causing mutation R345W in Efemp1, they are not observed in knock-out mice lacking Efemp1. A number of experimentally applied stress conditions have been shown to cause the formation of basal deposits in wild-type mice, including combinational treatments of high-fat diet (HFD) and cigarette smoke, or HFD and laser photochemical injury. This study is to test whether basal deposits develop in Efemp1 knock-out mice exposed to HFD/cigarette smoke or HFD/laser injury.
Efemp1 knock-out mice and wild-type littermates (control) were fed with a synthetic HFD. Mice of the same genotype at the same age were fed with standard laboratory rodent diet as controls. Beginning one month after starting the HFD, one group of mice under each condition was exposed to cigarette smoke daily for one month using a Teague Enterprises mouse smoking system (TE-10z), and another group of mice was subjected to photochemical injury every other day for two weeks from a 488 nm blue argon laser. Following the stress treatments, ocular phenotype analysis was performed to assess whether basal deposits developed in any of the mouse eyes.
In wild type mice, basal laminar deposits (BLD) were observed in the 18 month age group after exposure to HFD and cigarette smoke or laser injury. No BLD or other deposit was observed in younger age groups of wild type mice after the exposure. BLD was observed in 24 month old wild type mice with or without exposure to HFD/cigarette smoke or HFD/laser. In Efemp1 knock-out mice, BLD was not observed in any age groups with or without the exposure.
Mice lacking Efemp1 do not develop basal deposits. Environmental oxidative stressors (HFD/cigarette smoke or HFD/laser) known to cause BLD formation in wild type mice failed to induce BLD formation in Efemp1 knock-out mice. These results suggest that EFEMP1 is a central player in the development of BLD, and deletion of EFEMP1 is protective against the development of BLD.
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