Deletion of Efemp1 Is Protective Against the Development of Sub-RPE Deposits in Mouse Eyes

• Published in: Investigative ophthalmology & visual science Vol. 58; no. 3; pp. 1455 - 1461
• Main Authors: Stanton, James B, Marmorstein, Alan D, Zhang, Youwen, Marmorstein, Lihua Y
• Format: Journal Article
• Language: English
• Published: United States The Association for Research in Vision and Ophthalmology 01.03.2017
• Subjects: Animals; Disease Models, Animal; DNA - genetics; DNA Mutational Analysis; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Follow-Up Studies; Gene Deletion; Macular Degeneration - genetics; Macular Degeneration - metabolism; Macular Degeneration - pathology; Mice; Mice, Knockout; Mutation; Oxidative Stress; Pigment Epithelium of Eye - metabolism; Pigment Epithelium of Eye - pathology; Retinal Cell Biology; Time Factors
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.16-20955

EFEMP1 (fibulin-3) is mutated in Malattia Leventinese/Doyne's honeycomb retinal dystrophy (ML/DHRD), an inherited macular dystrophy similar to AMD. Both ML/DHRD and AMD are characterized by the presence of sub-RPE deposits. Efemp1 knockout mice do not develop sub-RPE deposits. This study was to test whether sub-RPE deposits can be induced in Efemp1 knockout mice by experimentally applied stress conditions that cause wild-type mice to develop sub-RPE deposits. Efemp1 knockout and control mice at 6, 18, or 24 months old were fed with a synthetic high-fat diet (HFD). Beginning 1 month after starting the HFD, one group of mice was exposed to cigarette smoke daily for 1 month, and another group of mice was subjected to photochemical injury every other day for 2 weeks from a 488-nm argon laser. After the treatments, histologic analysis was performed to assess whether sub-RPE deposits were induced. Basal laminar deposits (BLamDs), a form of sub-RPE deposits, were observed in the 18- and 24-month-old wild-type mice but not in Efemp1 knockout mice in any age groups after exposure to HFD and cigarette smoke or laser injury. Mice lacking fibulin-3 do not develop sub-RPE deposits. Environmental oxidative stressors (HFD/cigarette smoke or HFD/laser) known to cause BLamD formation in wild-type mice failed to induce BLamD formation in Efemp1 knockout mice. These results suggest that fibulin-3 is a central player in the development of BLamD, and deletion of fibulin-3 is protective against the development of BLamD.