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Oscar Manouchehrian, Karin Arner, Antonio Boza Serrano, Ulf Nilsson, Hakon Leffler, Tomas Deierborg, Linnea Taylor; Attenuation of photoreceptor cell death using the Galectin-3 inhibitor TD139 in an in vitro model of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2244.
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© ARVO (1962-2015); The Authors (2016-present)
Galectin-3 (Gal-3) is a multifunctional lectin which has been shown to mediate neuroinflammation and microglial phagocytosis in the brain. Our group recently showed that the absence of Gal-3 significantly increased neuronal survival, attenuated the glial inflammatory response, and conserved retinal architecture in mice subjected to chronic cerebral hypoperfusion. The adult porcine retinal tissue culturing system has been well described to display rapid neuronal degeneration and glial activation. Therefore, we wanted to explore the effects of blocking Gal-3 with a novel inhibitor, TD139, in this model.
Full-thickness retinal sheets (7x7mm) were isolated from adult pigs and cultured for 2 and 5 days in vitro with different concentrations of TD139 (5µl/10ml and 0.5µl/10ml) or DMSO added to the medium. Specimens were analyzed using morphological staining (HTX & eosin), and immunohistochemistry for neuronal cell survival (NeuN, Rec etc) and glial reactivity and inflammatory markers (CD45, Iba1, GFAP, TLR4, GS).
2 day specimens revealed no significant difference with regards to neuronal survival, glial reactivity or neuroinflammation. However, explants treated with the high concentration of TD139 for 5 days displayed a significant increased photoreceptor survival compared to solvent-only counterparts. Treated and non-treated groups displayed Gal-3 in microglia and Müller cells, with no significant difference in levels of expression. No differences were found between the groups with respect to other neuroinflammatory markers and glial reactivity.
We observed a significantly increased photoreceptor survival after 5 days in the TD139-treated specimens suggesting that Gal-3 may have potential as a pharmaceutical target for retinal diseases. Further research is required to elucidate the mechanism behind the rescue effect in this model.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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