title: Fibulin 2, a tyrosine O-sulfated protein, is up-regulated following retinal detachment.
abstract: Retinal detachment is the physical separation of the retina from the retinal pigment epithelium. It occurs during aging, trauma, or during a variety of retinal disorders such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, or as a complication following cataract surgery. This report investigates the role of fibulin 2, an extracellular component, in retinal detachment. A major mechanism for detachment resolution is enhancement of cellular adhesion between the retina and the retinal pigment epithelium and prevention of its cellular migration. This report shows that fibulin 2 is mainly present in the retinal pigment epithelium, Bruch membrane, choriocapillary, and to a lesser degree in the retina. In vitro studies revealed the presence of two isoforms for fibulin 2. The small isoform is located inside the cell, and the large isoform is present inside and outside the cells. Furthermore, fibulin 2 is post-translationally modified by tyrosine sulfation, and the sulfated isoform is present outside the cell, whereas the unsulfated pool is internally located. Interestingly, sulfated fibulin 2 significantly reduced the rate of cellular growth and migration. Finally, levels of fibulin 2 dramatically increased in the retinal pigment epithelium following retinal detachment, suggesting a direct role for fibulin 2 in the re-attachment of the retina to the retinal pigment epithelium. Understanding the role of fibulin 2 in enhancing retinal attachment is likely to help improve the current therapies or allow the development of new strategies for the treatment of this sight-threatening condition.
authors.affiliation: From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Kanan
authors.forename: Daniel
authors.initials: D
authors.lastname: Brobst
authors.forename: Zongchao
authors.initials: Z
authors.lastname: Han
authors.forename: Muna I
authors.initials: MI
authors.lastname: Naash
authors.forename: Muayyad R
authors.initials: MR
authors.lastname: Al-Ubaidi
mesh_terms: D000368:Aged; D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D011499:Protein Processing, Post-Translational; D012163:Retinal Detachment / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; C084612:fibulin 2; D014443:Tyrosine
keywords: Extracellular Matrix; Fibronectin; Post-translational Modification; Retinal Degeneration; Retinal Detachment; Retinal Pigment Epithelium; Tyrosine Sulfation