Abstract
Purpose: :
Toll-like receptor 3 (TLR3) is a pattern-recognition receptor that detects and binds double-stranded RNA. Recently it has been shown that signaling through TLR3 in vivo by various small interfering RNAs effectively suppresses choroidal neovascularization in a laser-injury mouse model. The purpose of this study is to investigate the expression of TLR3 in choroidal neovascular (CNV) membranes from patients with age-related macular degeneration.
Methods: :
Formalin-fixed, paraffin-embedded sections of CNV membranes from eight patients were immunostained using an anti-human TLR3 antibody. Expression in retinal pigment epithelial (RPE) cells, endothelial cells, and fibroblasts was evaluated in each CNV membrane. Additionally, eyes from four donors (aged 17, 53, 87 and 90 years) without CNV membranes were obtained from the Eye Bank of Canada and immunostained for TLR3 expression. Sections of placenta were used as a positive control.
Results: :
Strongly or moderately positive RPE cells were found in 7 of 8 (88%) CNV membranes. The fibroblasts and endothelial cells of all membranes were negative for TLR3. In the donor eyes, TLR3 was positive in the RPE of the three oldest patients. RPE cells were moderately positive adjacent to the ora serrata yet were completely negative at the posterior pole in these three patients. Additionally, TLR3 was expressed in photoreceptor inner segments and ciliary body non-pigmented epithelial cells in all four donor eyes.
Conclusions: :
To the best of our knowledge, this is the first study examining the expression of TLR3 in human CNV membranes. TLR3 was found in all but one CNV membrane and was expressed exclusively in RPE cells. Interestingly, no expression was observed in the RPE at the posterior pole of control eyes. This observation supports the idea that TLR3 may play an important role in the development of CNV. Further studies are necessary to fully elucidate the role of TLR3 in disease pathogenesis.
Keywords: choroid: neovascularization • age-related macular degeneration • immunohistochemistry