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Sorsby's fundus dystrophy mutant tissue inhibitors of metalloproteinase‐3 induce apoptosis of retinal pigment epithelial and MCF‐7 cells
Author(s) -
Majid Mohammed A,
Smith Valerie A,
Easty David L,
Baker Andrew H,
Newby Andrew C
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03359-8
Subject(s) - apoptosis , propidium iodide , microbiology and biotechnology , matrix metalloproteinase , mutant , retinal pigment epithelium , retinal , biology , chemistry , programmed cell death , biochemistry , gene
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 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.