Investigation of the efficacy of intraperitoneal administration of cryptotanshinone and decorin in oxygen-induced retinopathy model in rats

The aim of this study was to investigate the therapeutic efficacy of cryptotanshinone (CPT) and decorin (DCN) in an in vivo oxygen-induced retinopathy (OIR) rat model and to compare our results with bevacizumab which has proven success in premature retinopathy (ROP). A total of 35 Sprague Dawley rats, 7 in each group were used in this study. OIR model was created by exposing oxygen fluctuating between 50% and 10% for 14 days to 28 rats other than group A after their birth. Any of medical and surgical intervention was not performed in group A without OIR model and in group B with OIR model. Between the 15th and 17th days of the experiment intraperitoneal CPT, DCN and bevacizumab injections were applied respectively to each treatment group C, D and E with creating OIR model. For the quantitative assessment of retinal neovascularization the nuclei of neovascular endothelial cells on the vitreal side of the inner limiting membrane (ILM) were counted. Immunohistochemical analysis of vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) has been done according to a histoscore obtained by the intensity and extent of the immunoreactive stained cells. Neovascular endothelial cell nucleus was not observed in the vitreal surface of ILM in group A. In groups B, C, D and E, mean neovascular endothelial cell nuclei were observed 13,14±1,34, 7,28±0,75, 6,57±1,51 and 6,71±1,49, respectively. The mean number of neovascular endothelial cell nuclei decreased significantly in group C, D and E compared to group B (p<0,001). The mean number of neovascular endothelial cell nuclei was similar between group E and groups C and D (p=0,897, p=0,999, respectively). In immunohistochemical staining, the immunoreactivity of VEGF were 0,07±0,02, 0,97±0,21, 0,29±0,14, 0.37±0.12 and 0,23±0,17, respectively and TNF-α were 0,02±0,02, 1,11±0,36, 0,38±0,31, 0,37±0,13 and 0,62±0,21, respectively. In group B, VEGF and TNF-α immunoreactivity were significantly increased compared to group A (p<0,001). Immunoreactivity of VEGF and TNF-α was significantly decreased in group C, D and E compared to group B (p<0,001). VEGF and TNF-α immunoreactivities were similar between group E and groups C and D (VEGF; p=0,951, p=0,449, respectively and TNF-α; p=0,359, p=0,304, respectively). In conclusion, neovascularization was significantly suppressed by CPT or DCN treatment in the OIR model and this effect was similar when compared with bevacizumab. Our results are promising in terms of ROP treatment. However, further experimental studies on IV use and dose adjustment of these agents are required. Key words: Cryptotanshinone, decorin, retinopathy of premature, oxygen induced retinopathy