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: John D Hulleman
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 854 Pg. 153-8 ( 2016) ISSN: 0065-2598 [Print] United States
• PMID: 26427406 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• EFEMP1 protein, human
• Extracellular Matrix Proteins

Topics

• Animals
• Corneal Dystrophies, Hereditary (genetics, pathology, therapy)
• Disease Models, Animal
• Extracellular Matrix Proteins (genetics)
• Genetic Predisposition to Disease (genetics)
• Humans
• Macular Degeneration (genetics, pathology, therapy)
• Mice
• Mutation, Missense
• Optic Disk Drusen (congenital)
• Retina (metabolism, pathology)