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Ashok Kumar, Anuj Singla; Expression of Neurotrophins and Their Receptors in Bacterial Endophthalmitis: Role of Toll-like Receptor Signaling. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2769.
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Neurotrophins (NTs) play a pivotal role in protecting the retinal neurons from deleterious changes. Despite their promising therapeutic potential in various retinal diseases, including AMD and diabetic retinopathy, their role in bacterial endophthalmitis is largely unknown. The aim of this study is to determine the expression of neurotrophins and their receptors in bacterial endophthalmitis and to assess the involvement of Toll-like receptor signaling.
C57BL/6 mice were given intravitreal injections of S. aureus (RN 6390 strain) or various TLR ligands. At various time points post-infection, retinas were removed and subjected to RNA extraction and cDNA synthesis. The mRNA expression of neurotrophins was determined by Taqman probe based real-time PCR, whereas their protein levels were assessed by dot blot. To assess the source of neurotrophins in the retina, their expression and secretion were also assessed in cultured human retinal muller glia following S. aureus or TLR ligand challenge.
Expression of NTF3, NTF5, GDNF, and NGF in S. aureus infected WT mice was found to be significantly higher in comparison to the PBS-injected controls, reaching a peak around 12 h p.i.. However, no significant changewas observed in the expression levels of BDNF and CNTF. Intravitreal injection of ligands for TLR2, 3, 4, and 5 also increased the expression of NTs. Increased expression of neurotrophin receptors NGFR and NTrk2 at 12 h p.i. was also observed in S. aureus-infected retina. Similar to the in vivo study, stimulation of retinal Muller glia by bacteria or TLR ligands significantly increased the expression and secretion of NTs.
These findings demonstrate that the expression of NTs and their receptors is altered in bacterial endophthalmitis. Moreover, increased expression of NTs by TLR ligands suggest that TLR signaling is potentially involved in regulating their expression, which may provide novel therapeutic targets for preventing retinal damage in endophthalmitis.
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