July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Systematic treatment with trimethoprim/sulfamethoxazole (Ditrim) significantly inhibits spontaneous choroidal neovascularization (sCNV) in the JR5558 mouse model
Author Affiliations & Notes
  • YU SU
    Schepens Eye Research Institute,Massachusetts Eye and Ear,Harvard Medical School Affiliate, Boston, Massachusetts, United States
    Ophthalmic Center, Renmin Hospital of Wuhan University, Wuhan, Huibei Province, China
  • Franco Rossato
    Schepens Eye Research Institute,Massachusetts Eye and Ear,Harvard Medical School Affiliate, Boston, Massachusetts, United States
  • Ashley Mackey
    Schepens Eye Research Institute,Massachusetts Eye and Ear,Harvard Medical School Affiliate, Boston, Massachusetts, United States
  • Yin Shan Eric Ng
    Schepens Eye Research Institute,Massachusetts Eye and Ear,Harvard Medical School Affiliate, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   YU SU, None; Franco Rossato, None; Ashley Mackey, None; Yin Shan Eric Ng, None
  • Footnotes
    Support  This project is supported by Grimshaw Foundation AMD Research Grant from Mass Eye and Ear , Bright Focus Foundation AMD Research grant and NIH National Eye – Institute core grant (P30EYE003790). Yu Su is supported from China Scholarship Council (Grant No. 201606275174) and National Natural Science Foundation of China (Grant No. 81500744)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 70. doi:
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      YU SU, Franco Rossato, Ashley Mackey, Yin Shan Eric Ng; Systematic treatment with trimethoprim/sulfamethoxazole (Ditrim) significantly inhibits spontaneous choroidal neovascularization (sCNV) in the JR5558 mouse model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):70.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : We hypothesized that sub-clinical infection induces chronic inflammation of the retinal pigment epithelium (RPE), which could contribute to CNV pathogenesis. To investigate the role of sub-clinical infection in the development of CNV, the effect of systematic treatment with the broad-spectrum antibiotic Ditrim on sCNV development was determined using the JR5558 mouse model.

Methods : Two breeding groups of JR5558 mice were set up using mice from the same litter (F0) that were confirmed to have multiple CNV lesions (at least 10 CNV per eye) by fluorescein angiography (FA). The treatment groups (2 cages of F1 generation, 1 male and 1 female cage) were given Ditrim in the drinking water (0.96mg/ml) continuously from set up until the F1 mice were 30 days old, while the untreated control groups (2 cages of F1 generation) that were set up at the same time were given regular drinking water. FA was performed on F1 mice at P30 and eyes were collected for histological analyses. FITC-conjugated isolection B4 (IB4) and anti-CD45 antibody staining were used to identify sCNV and immune cells in the eyecup samples, respectively.

Results : From the FA analysis the number of sCNV lesions per eye in the treatment group was significantly reduced compared to the untreated control group (8.04±3.96 vs 16.17±3.31, P=0.0005). Immunohistological staining data from eyecups showed that both the number of CNV lesions (11.2±6.71 vs 30±10.40, P=0.0003) and the area of CNV per eye (21629.7±13475.07 pixel area vs 92697.25±57837.94 pixel area,P=0.0016) were significantly reduced in the Ditrim treatment group. Furthermore, the numbers of sCNV-associated CD45-positive leukocytes were significantly reduced in the treatment group when compared to the untreated control group (89.8±36.80 vs 283.625±52.57, P<0.001).

Conclusions : Our results demonstrate that systemic treatment with the broad-spectrum antibiotic Ditrim inhibits the development of sCNV lesions, which is correlated with the reduction of CNV-associated inflammation, suggesting that chronic sub-clinical infection could play an important role in CNV pathogenesis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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