title: Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy: Similarities to Age-Related Macular Degeneration and Potential Therapies.
abstract: Fibulin-3 (F3) is a secreted, disulfide-rich glycoprotein which is expressed in a variety of tissues within the body, including the retina. An Arg345Trp (R345W) mutation in F3 was identified as the cause of a rare retinal dystrophy, Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy (ML/DHRD). ML/DHRD shares many phenotypic similarities with age-related macular degeneration (AMD). The most prominent feature of ML/DHRD is the development of radial or honeycomb patterns of drusen which can develop as early as adolescence. Two independent mouse models of ML/DHRD show evidence of complement activation as well as retinal pigment epithelium (RPE) atrophy, strengthening the phenotypic connection with AMD. Because of its similarities with AMD, ML/DHRD is receiving increasing interest as a potential surrogate disease to study the underpinnings of AMD. This mini-review summarizes the current knowledge of F3 and points toward potential therapeutic strategies which directly or indirectly target cellular dysfunction associated with R345W F3.
authors.affiliation: Departments of Ophthalmology and Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., 75390-9057, Dallas, TX, USA. John.Hulleman@UTSouthwestern.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Hulleman
mesh_terms: D000818:Animals; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000473:pathology / Q000628:therapy; D051379:Mice; D020125:Mutation, Missense; D015594:Optic Disk Drusen / Q000151:congenital; D012160:Retina / Q000378:metabolism / Q000473:pathology
chemical_list: C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins
keywords: Age-related macular degeneration; Drusen; Fibulin-3; Malattia leventinese/Doyne honeycomb retinal dystrophy; Protein misfolding; Retinal degeneration; Therapeutics