Expression of TIMP3 mRNA is elevated in retinas affected by simplex retinitis pigmentosa.
To explore the molecular and cellular mechanisms associated with photoreceptor death in retinitis pigmentosa (RP), we have investigated altered transcriptional activity in RP retinas by a differential cDNA screening approach. We identified a clone (K222) showing over-expression in simplex RP retinas compared with controls. K222 encodes a partial cDNA of the human tissue inhibitor of metalloproteinases-3 (TIMP3) gene, a member of a family of genes implicated in extracellular matrix (ECM) remodelling. Increased expression of TIMP3 in degenerating RP retinas may reflect restructuring of the ECM architecture, and disruption of photoreceptor-matrix interactions could contribute to activation of apoptotic cell death processes.
Jones
S E
SE
Department of Pharmacology, Rayne Institute, UMDS, Guy's Hospital, London, UK.
Jomary
C
C
Neal
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001483:Base Sequence; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D018076:DNA, Complementary / Q000032:analysis; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012160:Retina / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D019717:Tissue Inhibitor of Metalloproteinase-3
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D008666:Metalloendopeptidases