Purchase this article with an account.
Alecia Cutler, Bela Anand-Apte, Vera Bonilha, Dilara Hatipoglu, Heidi Stoehr; Hyaluronan and Tissue Inhibitor of Metalloproteinases-3 in Sorsby's Fundus Dystrophy and AMD. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6079.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine the effects of alterations in TIMP-3 on hyaluronic acid (HA) in the retina.
ARPE-19 cells were transfected with either SFD S156C-TIMP-3, wild-type TIMP-3 or the empty vector. Cells were stained for HA with HA binding protein and imaged by confocal microscopy. Posterior eye sections from wild type, TIMP-3 knockout and SFD-TIMP-3 mice were analyzed for HA expression by immunohistochemistry (IHC) using biotinylated HA binding protein. Sections of postmortem human donor eyes with and without AMD were also stained for HA using IHC as above.
Increased HA levels were observed in the extracellular matrix (ECM) of ARPE-19 cells transfected with SFD TIMP-3. Increased expression of HA was observed in Bruch’s membrane and RPE in both the TIMP-3 knockout and SFD TIMP-3 mice. Interestingly, HA expression was also increased in the retina and choroid of the human eyes with wet AMD but not in patients with dry AMD.
The increased amounts of HA in ARPE cells, TIMP-3 deficient mice and SFD mutant mice as well as in human wet AMD eyes suggests that HA may play a significant role in the development of AMD and SFD. Strategies to inhibit this effect may be useful for treating AMD and SFD.
This PDF is available to Subscribers Only