Expert Reviews in Molecular Medicine

 


Review Article

TIMP3 mutation in Sorsby's fundus dystrophy: molecular insights

Zheng Li a1, Michael P. Clarke a2, Michael D. Barker a3 and Norman McKie a1c1
a1 Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle, NE4 6BH, UK.
a2 Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK.
a3 Academic Unit of Pathology, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Rd, Sheffield, S10 2RX, UK.

Abstract

Sorsby's fundus dystrophy (SFD) is a rare autosomal dominant disorder that results in degeneration of the macular region of the retina, with onset usually in the fourth to fifth decade of life. It leads to the rapid loss of central vision, often followed by further loss of peripheral vision. SFD shares several pathological features commonly found in the ‘wet’ or exudative form of age-related macular degeneration (AMD), the most common cause of blindness in the elderly in developed countries. These phenotypic similarities have led to SFD being proposed as an acceptable genetic model for AMD. Whereas AMD appears to have a complex aetiology, with both genetic and environmental factors playing a role, SFD has been shown to be a single-gene disorder, linked to mutations in exon 5 of the tissue inhibitor of metalloproteinases 3 (TIMP3) gene on chromosome 22q12-q13. This review confines itself to a discussion of the known biochemical properties of the wild-type and SFD TIMP3 proteins and attempts to relate these to the pathology encountered in SFD patients. We also discuss briefly how, despite the lack of inherited mutations in the structural gene, the TIMP3 protein might play a role in the onset and progression of AMD.


Key Words: TIMP3; Sorsby's Fundus Dystrophy; Macula; Retina; Degeneration; Mechanism.

Correspondence:
c1 Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle, NE4 6BH, UK. Tel: +44 (0)191 222 7541; Fax: +44 (0)191 222 5455; E-mail: norman.mckie@ncl.ac.uk

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