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Cristante, E.

Publications and source records attributed to Cristante, E..

2 recordsLinked to original sources

Improved daylight vision following AAV-mediated expression of R9AP in murine rod photoreceptors

Cone photoreceptors mediate daylight vision and are the primary cells responsible for vision in humans. Cone dysfunction leads to poor quality daylight vision because rod photoreceptors become saturated and non-functional at high light levels. Here we demonstrate that in mice lacking cone function, AAV-mediated over-expression of Rgs9-anchor protein (R9AP), a critical component of the GTPase complex that mediates the deactivation of the phototransduction cascade, results in desensitization of rod function and a "photopic shift" of the rod-driven electroretinogram. This treatment enables rods to respond to brighter light (up to [~]2.0 log) with increased visually-evoked cortical responses to high intensity stimulation. These results suggest that AAV-mediated transfer of R9ap into rods might be used to improve daylight vision in humans visually handicapped by cone dysfunction.

bioengineering↗

Syndecan-4 is required for VE-Cadherin trafficking during pathological angiogenesis

New blood vessel formation, or angiogenesis, is characteristic of chronic diseases such as cancer, rheumatoid arthritis and vision-threatening conditions. Vascular Endothelial growth factor (VEGFA) and its receptor VEGFR2 drive neovascularization and hyperpermeability in these pathologies. One consequence of VEGFR2 activation is decreased stability of endothelial cell (EC) junctions through internalization of VE-Cadherin, allowing re-arrangement of sprouting ECs. Evidence suggests roles for heparan sulfate proteoglycans in angiogenesis and we show that Syndecan-4 (SDC4) expression is upregulated during pathological angiogenesis and is required for efficient VE-Cadherin internalization. Angiogenic responses in both tumor and neovascular eye disease models are impaired in Syndecan-4 null mice (Sdc4-/-), as is dermal hyper-permeability response to VEGFA. We show SDC4 resides at EC junctions and interacts with VE-Cadherin, an association lost upon VEGFA-stimulation, and this is SDC4 phosphorylation-dependent. Finally, we show that pathological angiogenic responses can be inhibited in a model of age-related macular degeneration by targeting SDC4. This study identifies SDC4 as a key component of VE-Cadherin trafficking and, as such, a critical regulator of pathological angiogenesis and vascular permeability.

cell biology↗