Purchase this article with an account.
Pachiappan Arjunan, Zhongshu Tang, Lijin Dong, Zhijian Wu, Pamela M Martin, Cutler W Christopher, Xuri Li; Neuro and vasoprotective effects of vascular endothelial growth factor-B in Retinitis pigmentosa . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3646. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa is a heterogeneous inherited retinal dystrophy characterized by progressive loss of photoreceptors and subsequent degeneration of retinal pigmented epithelial cells. Despite its early discovery and high sequence homology to the other VEGF family members, the molecular mechanism of VEGF-B in retinal and blood vessel degeneration in a disease model of retinitis pigmentosa has not been delineated yet. Thus, we aimed to test our hypothesis that either VEGF-B functions as a potent photoreceptors/vascular survival or rescue factor in retinal degenerative disease.
We used different animal models and cultured cells to show that VEGF-B is a potent vascular protective and survival factor. Blood vessel densities and retinal thickness were measured by IF and H&E staining in VEGF-B, AAV2+VEGF-B treated rd1 and VEGF-B-/- mice retinae compared with their respective controls. TUNEL assay was performed in VEGF-B & anti-VEGF-B injected mice retinae. VEGF-B regulated genes related to neurotrophic/survival, angiogenic, apoptotic, antioxidants & oxidative stress were tested using pathway focused PCR array and quantified by qPCR & western. Role of VEGF-B mediated survival of photoreceptors and RPE cells were examined after VEGF-B and H2O2 treatment using MTT and confirmed by qPCR.
Increased retinal thickness was observed in VEGF-B treatment whereas reduced in VEGFB-/- mice compared with their littermates. VEGF-B treatment rescues retinal and vascular cells from apoptosis and preserve both the photoreceptors and blood vessels in rd1 mice. VEGF-B activates the expression of the protein and antioxidant defense, cell survival related genes whereas inhibits oxidative damage, cell death related genes in rd1 mic retinae. Western & IF confirms VEGF-B specificity and increased rho-4D2 positivity, respectively, in AAV2+VEGF-B treated rd1 mice retina compared with GFP.
Our finding shows that VEGF-B treatment up-regulates the array of survival & antioxidant related genes, which activates the glutathione defense system and rescues the retinal vasculature and protect photoreceptor cells in rd1 mice. Thus, our data shows VEGF-B play a pivotal role in conserving vascular survival under pathological condition and may be of therapeutic value in treating retinal degenerative disease Retinitis pigmentosa.
This PDF is available to Subscribers Only