Absence of SPARC leads to impaired lens circulation.
SPARC is a matricellular glycoprotein involved in regulation of extracellular matrix, growth factors, adhesion, and migration. SPARC-null mice have altered basement membranes and develop posterior sub-capsular cataracts with cell swelling and equatorial vacuoles. Exchange of fluid, nutrients, and waste products in the avascular lens is driven by a unique circulating ion current. In the absence of SPARC, increased circulation of fluid, ions, and small molecules led to increased fluorescein distribution in vivo, loss of resting membrane polarization, and altered distribution of small molecules. Microarray analysis of SPARC-null lenses showed changes in gene expression of ion channels and receptors, matrix and adhesion genes, cytoskeleton, immune response genes, and cell signaling molecules. Our results confirm the hypothesis that the regulation of SPARC on cell-capsular matrix interactions can increase the circulation of fluid and ions in the lens, and the phenotype in the SPARC-null mouse lens is the result of multiple intersecting functional pathways.
Greiling
Teri M S
TM
University of Washington, Department of Biological Structure, Seattle, WA 98195-7420, USA. teri@u.washington.edu
Stone
Brad
B
Clark
John I
JI
D000818:Animals; D002386:Cataract / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D019793:Fluorescein; D020869:Gene Expression Profiling; D018698:Glutamic Acid / Q000378:metabolism; D007903:Lens Capsule, Crystalline / Q000378:metabolism / Q000503:physiopathology; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014617:Vacuoles / Q000378:metabolism
D005136:Eye Proteins; D015676:Osteonectin; D018698:Glutamic Acid; D019793:Fluorescein