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.