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Claudia Prospero Ponce, Dan Gombos, Aravindh Ganapathy, Patricia Chevez-Barrios; High Risk Retinoblastoma: Correlation Between Expression of Angiogenic Factors and Neovascular Glaucoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1257.
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To analyze the expression of angiogenic factors in the eye(retina, iris and tumor) in retinoblastoma(Rb) cases with high risk features(HRF) and Non-HRF. Angiogenesis is essential for tumor growth and metastasis. In Rb tumors, angiogenesis may complicate the clinical presentation by inducing glaucoma due to iris neovascularization(NVI) with secondary peripheral synechiae(PAS) formation. The expression of angiogenic factors in specific ocular and tumor cells determines the tumor growth and complications.
We analyzed 10 Rb eyes with NVI and glaucoma. These were classified as HRF(4/10) if they showed invasion to choroid and/or optic nerve post lamina cribrosa. Double staining by immunohistochemistry was performed with vascular endothelial growth factor(VEGF)-glial fibrillary acidic protein(GFAP; glial cells) and VEGFR-2(receptor)-CD105(endoglin; new vessels). Quantitative analysis per area (μm2) of expression and co-localization of angiogenic factors with different cell types was performed using Image-J software(NIH).
VEGF expression: The highest expression is seen in the tumor of HRF eyes. The iris shows about equal expression in both groups. The retina however, shows less expression of VEGF in HRF cases. VEGF-GFAP co-expression: In tumors, the co-expression is higher in HRF eyes. This co-expression is higher in Non-HRF retina. VEGFR-2 expression: Tumor and iris in HRF eyes have higher expression than the Non-HRF. The retina shows lower expression in HRF. CD105 expression: Tumors demonstrate similar expression(average in μm2: HRF 144 vs Non-HRF 132). In the iris, the CD105 is expressed ~60% more than in the Non-HRF. In the HRF retina, the vessels have lower expression than Non-HRF; The expression is ~95% lower in HRF than in Non-HRF at the level of tumor invasion into the retina. CD105-VEGFR-2 co-expression: There is higher co-expression in HRF eyes in the tumor(average in μm2: HRF 68 vs Non-HRF 14) and in the iris(average in μm2: HRF 54 vs. Non-HRF 38).
Eyes with HRF show increased expression of VEGF and its receptor VEGFR-2 in both the tumor and the iris. CD105 expression(newly formed vessels) is elevated in tumors but is particularly higher in the iris of HRF eyes. Therefore in HRF eyes, treatments that target cells expressing angiogenic factors and/or the factors alone may be useful to prevent complications such as development of neovascular glaucoma.
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