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Toan Phan, Joan Stein-Streilein; Retinal Laser Burn (RLB) alter inflammatory Toll-like receptors (TLRs) in the retina in a Substance P dependent manner. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3579.
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To investigate trauma (retinal laser burn) induced substance P (SP) dependent mechanisms that cause the loss of ocular immune privilege. To test the hypothesis that SP causes an exaggeration of the immune response in the eye post RLB by influencing the expression of inflammatory TLRs.
Four laser spots (810 nm diode laser, 50mW, 50ms, 200 µm dot size) were delivered to the right eye of the experimental (Wild type C57BL/6J or Substance P KO mice) mice. The burned (ipsilateral) and non-burned (contralateral) eyes of RLB mice as well as naïve (untreated) eyes were enucleated 24h , 48h or 72 h later. The neural retinas of ipsilateral and contralateral eyes were dissected and qRT-PCR was performed to assess for changes in TLR2 and TLR4 mRNA expressions. qRT-PCR of TLR2 and TLR4 mRNA expression was also performed on both eyes of Wild type B6 mice that received anterior chamber(a.c.) inoculation of ovalbumin(OVA), SP, or OVA with SP in the ipsilateral eye.
The baseline negative mRNA expression for TLR2 and TLR4 was determined in eyes of untreated mice. Post RLB, there was an increase in TLR2 and TLR4 mRNA expressions in the ipsilateral eye beginning at 24h and increased with time through 48h and 72 h. Changes in TLR2 and TLR4 expressions in the contralateral eye were slightly delayed but also increased. Unlike B6 WT, SP KO mice did not show a significant increase in TLR2 or TLR4 mRNA expression 48 h post RLB. 48 h post inoculation of SP increased TLR2 and TLR4 mRNA expression in both eyes of B6 WT mice.
We showed that RLB upregulates TLR2 and TLR4 in WT but not SP KO mice . Also, direct inoculation of SP induced TLR2 and TLR4 upregulation in both eyes. These data support the posit that RLB induces an exaggerated inflammatory response in both burned and nonburned eyes by upregulating inflammatory TLRs in a SP dependent manner. Thus we can conclude that Substance P contributes to the alteration in immune homeostasis in the retina by modifying the type of TLR expressed and allowing inflammatory TLRs to be available to bind danger signals released into the eye post RLB. Antagonists to inflammatory toll-like receptors or NKR1.1 (Substance P receptor) may be therapeutic in relieving the immune inflammatory sequelae post ocular trauma such as laser injury.
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