Journal
EXPERIMENTAL AND THERAPEUTIC MEDICINE
Volume 13, Issue 6, Pages 3360-3368Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2017.4431
Keywords
diabetic retinopathy; ranibizumab; retinal ganglion cells; type IV collagen; vascular endothelial growth factor A
Categories
Funding
- National Natural Science Foundation of China [81460092, 81160118, 81400372]
- Clinical Medicine Research Special-purpose Foundation of China [L2012052]
- Jiangxi Province Voyage Project [2014022]
- Jiangxi province Degree and Postgraduate Education Reform Project [2015]
- Science and Technology Platform Construction Project of Jiangxi Province [2013116]
- Youth Science Foundation of Jiangxi Province [20151BAB215016]
- Technology and Science Foundation of Jiangxi Province [20151BBG70223]
- Jiangxi Province Education Department Scientific Research Foundation [GJJ14170]
- Health Development Planning Commission Science Foundation of Jiangxi Province [20155154]
- Scholar Project of Ganjiang River
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The aim of the present study was to investigate the effect of intravitreal injection of ranibizumab on retinal ganglion cells and microvessels at the early stage of diabetic retinopathy (DR) in rats with streptozotocin-induced diabetes mellitus (DM). DM was induced by a single intraperitoneal injection of 60 mg/kg body weight streptozotocin. A total of 80 diabetic rats were randomly assigned to four treatment groups (n=20 in each group) and were treated with an oculus dexter intravitreal injection of ranibizumab. Groups A and B were injected with ranibizumab two and four weeks after DM-induction, respectively, while groups a and b (controls) were injected with phosphate-buffered saline at the same time points. In addition, 20 normal rats were assigned to group N (blank control; without intraocular injection). Vitreous humors were isolated for vascular endothelial growth factor (VEGF) -A ELISA and retinas were obtained for hematoxylin and eosin staining, periodic acid-Schiff staining and fluorescence imaging techniques at six and eight weeks after the onset of DM. At six and eight weeks, a significantly increased in retinal ganglion cells (RGCs) was observed in group A compared with group a (P<0.01), and in group B compared with group b (P<0.01). In addition, there was a significant difference in the RGC level between groups A and B at six weeks after DM induction (P<0.01), but not at eight weeks (P>0.05). VEGF-A concentrations in rat vitreous humors were significantly lower in groups A and B compared with groups a and b at six and eight weeks after DM induction (P<0.01). Furthermore, the ratio of endotheliocytes to pericytes in groups A and B was significantly lower compared with groups a and b at six and eight weeks (P<0.05). Furthermore, it was also demonstrated that type IV collagen-positive strands were not present in group A during the eight-week observation period, which was significantly different from groups a, b and B (P<0.01). In conclusion, intravitreal injection of ranibizumab at a very early stage of DR in streptozotocin-induced DM rats slowed the progression of DR by reducing vascular regression or damage and maintaining RGC numbers, as well as reducing VEGF-A concentrations.
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