Abstract
Vascular endothelial growth factor (VEGF) is a major regulator in retinal and choroidal angiogenesis, which are common causes of blindness in all age groups. Recently anti-VEGF treatment using anti-VEGF antibody has revolutionarily improved the visual outcome in patients with vaso-proliferative retinopathies. Herein, we demonstrated that bevacizumab as an anti-VEGF antibody could inhibit differentiation of retinoblastoma cells without affection to cellular viability, which would be mediated via blockade of extracellular signal-regulated kinase (ERK) 1/2 activation. The retinoblastoma cells expressed VEGFR-2 as well as TrkA which is a neurotrophin receptor associated with differentiation of retinoblastoma cells. TrkA in retinoblastoma cells was activated with VEGF treatment. Interestingly even in the concentration of no cellular death, bevascizumab significantly attenuated the neurite formation of differentiated retinoblastoma cells, which was accompanied by inhibition of neurofilament and shank2 expression. Furthermore, bevacizumab inhibited differentiation of retinoblastoma cells by blockade of ERK 1/2 activation. Therefore, based on that the differentiated retinoblastoma cells are mostly photoreceptors, our results suggest that anti-VEGF therapies would affect to the maintenance or function of photoreceptors in mature retina.
Highlights
As originally discovered as an endothelial-specific growth factor [1], vascular endothelial growth factor (VEGF) plays a critical role in physiological and pathological angiogenesis [2]
Trk A expression as a negative control [24], TrkA was highly expressed in both retinoblastoma cell lines of Y79 and SNUOTRb1. (Figure 1A) to determine whether VEGFR-2 and TrKA, as a neurotrophin receptor are expressed in retinoblastoma cells, the expression of VEGFR-2 and TrkB was measured in retinoblastoma cell lines, Y79 and SNUOT-Rb1, by western blot analysis
Base on our reports that differentiation of retinoblastoma cells would be mediated by extracellular signal-regulated kinase (ERK) 1/2 activation [23,25], we addressed whether ERK 1/2 activation is changed in differentiated retinoblastoma cells by 1 mg/ml bevacizumab
Summary
As originally discovered as an endothelial-specific growth factor [1], vascular endothelial growth factor (VEGF) plays a critical role in physiological and pathological angiogenesis [2]. VEGF generated from the nervous system has been documented to function in neurons as well as endothelial cells [3]. VEGF seems to share common molecular triggers and signaling pathways in neurons and endothelial cells of the nervous system as our previous suggestion [4,5]. The neurotrophic and neuroprotective effect of VEGF could be mediated through its tyrosine kinase receptor, VEGFR-2 which is widely expressed in neurons and glias [6]. With recent observations to unravel the direct effect of VEGF on neurons and glias, VEGF appears to be essential for neuronal development and survival in physiological and pathological conditions [7]. With recent development of antiVEGF therapy using anti-VEGF antibody, the visual outcome in patients with retinal and choroidal vascular diseases has been revolutionarily improved [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
