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Ronald Hobbs, Saad Munzar, Genevieve S. Ball, Faizah N. Bhatti; MyD88 Mediated TLR2 and TLR4 Activation Leads to Expression of Surfactant Protein A in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2533.
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© ARVO (1962-2015); The Authors (2016-present)
We have successfully shown the developmental pattern of Surfactant Proteins A (SP-A) and D (SP-D) in the mouse retina. These proteins belong to the superfamily of collectin molecules which are involved in innate host defense. SP-A activity can be mediated by toll like receptor (TLR) signaling, especially by TLR2 and TLR4. MyD88 is an important intermediary between TLR2/TLR4 activation and NF B signaling. NF B is a nuclear transcription factor for many collectin molecules including SP-A. No data currently exists regarding surfactant protein signaling pathways in the retina. Our objective was to study the in vivo role of TLR2 and TLR4 activation on retinal SP-A expression using TLR ligands in the retinas of TLR2-/-, TLR4-/- and MyD88-/- mice.
For this study 6-10 week old C57BL/6J (WT) and TLR2-/-, TLR4-/- and MyD88-/- mice were used. Intravitreal injections of the TLR2 ligand PamC3 and the TLR4 ligand LPS were performed with PBS as control in all the mice. After euthanasia, retinas were harvested at 6, 12, 18 and 24 hours after injection and SP-A levels were measured in whole retinal homogenate by ELISA. Results were analyzed by Student's t-test with a p value of <0.05 significance.
Intravitreal injection of LPS in WT mice resulted in a fourfold increase in retinal SP-A levels as compared to control (p value 0.028) with a peak observed at 12 hours, while PamC3 resulted in a two-fold increase of SP-A as compared to control (p value 0.036) with a peak at 6 hours. In MyD88-/- mice, injection with LPS and PamC3 led to no increase in SP-A compared to control.
In the mouse retina, TLR2 as well as TLR4 activation leads to increased expression of SP-A. As this is attenuated in MyD88-/- mice, we hypothesize that this effect is mediated via TRAF6 and NF B. This needs further investigation to examine the precise mechanisms involved. We are now in the process studying these pathways in SP-A-/- null mice and looking to determine if hyperoxia and stress also up regulate this anti-inflammatory protein.
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