Sorsby's fundus dystrophy mutant tissue inhibitors of metalloproteinase-3 induce apoptosis of retinal pigment epithelial and MCF-7 cells

Majid, M. A., Smith, V. A., Easty, D. L., Baker, A. H. and Newby, A. C. (2002) Sorsby's fundus dystrophy mutant tissue inhibitors of metalloproteinase-3 induce apoptosis of retinal pigment epithelial and MCF-7 cells. FEBS Letters, 529(2-3), pp. 281-285. (doi: 10.1016/S0014-5793(02)03359-8)

Abstract

C-terminal domain tissue inhibitor of metalloproteinases-3 (TIMP-3) mutations cause the rare hereditary blindness Sorsby’s fundus dystrophy (SFD), which involves loss of retinal pigment epithelial (RPE) cells. Since wild-type TIMP-3 causes apoptosis, we investigated whether SFD TIMP-3 might kill RPE and other cells. Plasmid-mediated overexpresion of Ser-156, Gly-167, Tyr-168 and Ser-181 SFD mutant TIMP-3 decreased RPE viability to 22±8, 20±6, 32±5, 30±12% (SFD mutants all <i>P</i><0.01 versus wild-type 50±8%) and similarly increased propidium iodide staining and in situ end labelling. Adenovirus-mediated overexpression of the Gly-167 mutant also caused RPE apoptosis dose-dependently. Apoptosis of RPE cells might therefore contribute to the pathology of SFD.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Baker, Professor Andrew
• Authors: Majid, M. A., Smith, V. A., Easty, D. L., Baker, A. H., and Newby, A. C.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: FEBS Letters
• Publisher: Elsevier BV
• ISSN: 0014-5793
• ISSN (Online): 1873-3468
• Published Online: 13 September 2002