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

Mohammed A Majid; Valerie A Smith; David L Easty; Andrew H Baker; Andrew C Newby

doi:10.1016/s0014-5793(02)03359-8

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

FEBS Lett. 2002 Oct 9;529(2-3):281-5. doi: 10.1016/s0014-5793(02)03359-8.

Authors

Mohammed A Majid¹, Valerie A Smith, David L Easty, Andrew H Baker, Andrew C Newby

Affiliation

¹ Institute of Ophthalmology, University of Bristol, Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK.

PMID: 12372614
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 overexpression 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 P<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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / physiology*
Fundus Oculi*
Humans
Pigment Epithelium of Eye / cytology
Pigment Epithelium of Eye / metabolism*
Retinal Diseases / metabolism*
Tissue Inhibitor of Metalloproteinase-3 / chemistry
Tissue Inhibitor of Metalloproteinase-3 / physiology*
Tumor Cells, Cultured

Substances

Tissue Inhibitor of Metalloproteinase-3