Computer-aided quantification of retinal neovascularization

Rodent models of retinal angiogenesis play a pivotal role in angiogenesis research. These models are a window to developmental angiogenesis, to pathological retinopathy, and are also in vivo tools for anti-angiogenic drug screening in cancer and ophthalmic research. The mouse model of oxygen-induced retinopathy (OIR) has emerged as one of the leading in vivo models for these purposes. Many of the animal studies that laid the foundation for the recent breakthrough of anti-angiogenic treatments into clinical practice were performed in the OIR model. However, readouts from the OIR model have been time-consuming and can vary depending on user experience. Here, we present a computer-aided quantification method that is characterized by (i) significantly improved efficiency, (ii) high correlation with the established hand-measurement protocols, and (iii) high intra- and inter-individual reproducibility of results. This method greatly facilitates quantification of retinal angiogenesis while at the same time increasing lab-to-lab reproducibility of one of the most widely used in vivo models in angiogenesis research.

[1]  P. Carmeliet,et al.  Oxygen-Induced Retinopathy in Mice: Amplification by Neonatal IGF-I Deficit and Attenuation by IGF-I Administration , 2009, Pediatric Research.

[2]  Lois E. H. Smith,et al.  Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis , 2007, Nature Medicine.

[3]  Lois E. H. Smith,et al.  Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[4]  K. Yu,et al.  Diltiazem reduces retinal neovascularization in a mouse model of oxygen induced retinopathy. , 1999, Current eye research.

[5]  L. Aiello,et al.  Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Martin Friedlander,et al.  T2-TrpRS inhibits preretinal neovascularization and enhances physiological vascular regrowth in OIR as assessed by a new method of quantification. , 2006, Investigative ophthalmology & visual science.

[7]  Lois E. H. Smith,et al.  Oxygen-induced retinopathy in the mouse. , 1994, Investigative ophthalmology & visual science.

[8]  R. Ali,et al.  Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1 , 2002, Gene Therapy.

[9]  Paolo Valerio,et al.  Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic. , 2006, Current medicinal chemistry.

[10]  H. Shapiro,et al.  Ranibizumab for Neovascular Age-Related Macular Degeneration (AMD): Optical Coherence Tomography (OCT) vs. Visual Acuity (VA) Changes in PIER Study , 2008 .

[11]  Philip J Rosenfeld,et al.  Ranibizumab for neovascular age-related macular degeneration. , 2006, The New England journal of medicine.

[12]  Lois E. H. Smith,et al.  Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor , 1999, Nature Medicine.

[13]  H. Suzuki,et al.  Effects of intraocular or systemic administration of neutralizing antibody against vascular endothelial growth factor on the murine experimental model of retinopathy. , 1999, Life sciences.

[14]  P. Campochiaro,et al.  Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization. , 2000, The American journal of pathology.

[15]  M. Capogrossi,et al.  Marked inhibition of retinal neovascularization in rats following soluble‐flt‐1 gene transfer , 2004, The journal of gene medicine.

[16]  Donald Kennedy,et al.  Breakthrough of the Year , 2007, Science.

[17]  G. Haddad,et al.  Genetic and pharmacological inhibition of JNK ameliorates hypoxia-induced retinopathy through interference with VEGF expression , 2009, Proceedings of the National Academy of Sciences.

[18]  D Kennedy,et al.  Breakthrough of the Year , 2003, Science.

[19]  S. Pri-chen,et al.  An increase in superoxide dismutase ameliorates oxygen-induced retinopathy in transgenic mice , 2005, Eye.

[20]  Lois E. H. Smith,et al.  Erythropoietin deficiency decreases vascular stability in mice. , 2008, The Journal of clinical investigation.