Drug Modification of Angiogenesis in a Rat Cornea Model

Schwartz, Shulamit; George, Jacob; Ben-Shoshan, Jeremy; Luboshits, Galia; Avni, Isaac; Levkovitch-Verbin, Hani; Ziv, Hana; Rosner, Mordechai; Barak, Adiel

doi:10.1167/iovs.06-1337

Cited by 17 publications

(6 citation statements)

References 20 publications

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“…Introduced in 1974 by Gimbrone et al ,27 this method was originally developed for rabbits, although it has been adapted for both rats28 and mice 29. An advantage of the corneal angiogenesis assay over the CAM assay is that the cornea is avascular.…”

Section: Existing In Vivo Assays Of Angiogenesismentioning

confidence: 99%

Microcomputed Tomography Characterization of Neovascularization in Bone Tissue Engineering Applications

Young

Kretlow

Nguyen

et al. 2008

Tissue Engineering Part B: Reviews

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Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs.

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Section: Existing In Vivo Assays Of Angiogenesismentioning

confidence: 99%

Microcomputed Tomography Characterization of Neovascularization in Bone Tissue Engineering Applications

Young

Kretlow

Nguyen

et al. 2008

Tissue Engineering Part B: Reviews

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“…As shown in Figure 3 a , in the circle area of 10 mm diameter around the filter paper disc, the formation of novel blood vessels (pointed with black arrows) was obviously blocked by indirubin (5 and 10 μg/disc), suggesting that indirubin inhibited CAM angiogenesis. To further confirm the effect of indirubin on antiangiogenesis in vivo , we subsequently performed the mice corneal micropocket assay which is considered as the “gold standard” for in vivo analysis of angiogenesis 29. Our results showed that the density and the length of the neovasculature in indirubin‐treated group were much less than that of control group (Fig.…”

Section: Resultsmentioning

confidence: 86%

Reply:

2013

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We appreciate the observations made by Harris et al. regarding the differences in claudin-1 expression in human liver between the report by Reynolds et al. 1 and our work. 2 The main objective of our study was to assess the potential changes in tight junction proteins claudin-1 and occludin following hepatitis C virus (HCV) graft infection. We observed an increased expression of claudin-1 and occludin over time in HCV-infected patients. The increase in claudin-1 was particularly significant in individuals with cholestatic hepatitis. It is important to notice that when we applied very low threshold values to create a surface for quantification, it was almost impossible to discriminate basolateral claudin-1 staining from either unspecific staining or tissue autofluorescence. More restrictive thresholding guarantees the quantification of specific signal, although it should be noted that this is at the expense of decreased sensitivity. Thus, it is a possibility that we may have underestimated claudin-1 expression in the basolateral membrane because we quantified fluorescence intensity using a single threshold value.The detection of minor pools of basolateral claudin-1 is an interesting finding. Further studies are required to investigate the role of nonjunctional claudin-1 in HCV entry and the physiopathological consequences of increased levels of claudin-1 expression in HCV disease progression. Harrington et al. discuss the clinical relevance of detectable, but not quantifiable, hepatitis C viral (HCV) RNA during treatment with the two recently approved direct-acting antivirals (DAAs), boceprevir and telaprevir. 1 The clinical trials used to assess the efficacy of these new DAAs were not designed to assess response-guided therapy using the less than lower limit of quantification [LLOQ] cutoff. However, a viremia below the LLOQ, but with detectable amounts of virus, clearly indicates that peripheral clearance has not occurred and, by implication, that replicating virus is still present in the liver. The endpoint for the LLOQ for most clinical trials is 25 IU/mL (1.39 log 10 ). The reduction in the sustained virological response (SVR) rate between those patients that have a viremia less than the LLOQ and those that have no detectable viremia clearly indicates that lack of peripheral suppression is still a good surrogate for persistence. No assay currently available detects HCV down to a level of 0.001 IU/mL, as outlined in Figure 1 of Harrington et al. 1 We have assessed the decreasing confidence interval (CI) associated with HCV reverse-transcriptase polymerase chain reaction (RT-PCR) on a panel of characterized HCV genotype 1b samples (100, 37, 10, 3.7, 1, 0.37, and 0.04 IU/mL; AcroMetrix; Invitrogen, Carlsbad, CA). The test platform was the Roche AmpliPrep and TaqMan 48 (Roche Molecular Diagnostics, Pleasanton, CA). Tests were replicated between 13 and 25 times. A 100% hit rate was achieved for the 100-and 37-IU/mL samples. A 95% CI was achieved at 9.914 (range, 5.737-26.578; n ¼ 13). Probit analysis yield...

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“…Schwartz et al 28 studied the effect of timolol, a nonselective beta-adrenergic antagonist, on corneal NV. Timolol was shown to have no inhibitory effect on NV.…”

Section: Discussionmentioning

confidence: 99%