Octreotide Inhibits Choroidal Neovascularization in Rats

Qu, Yi; Zhang, Shuihua; Xu, Xin; Wang, Hong; Li, Jinghai; Zhou, Fang; Wei, Fang

doi:10.1159/000219683

Cited by 9 publications

(8 citation statements)

References 76 publications

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“…Although we did not find any of the more commonly reported side effects like severe gastrointestinal problems (for example, necrotizing enterocolitis) [19] , hypothyroidism, cholelithiasis [20,21] and retinal problems [22,23] , we did find a relatively high occurrence of PPHN which required treatment.…”

Section: Discussioncontrasting

confidence: 77%

Is Octreotide Treatment Useful in Patients with Congenital Chylothorax?

2011

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Background: Congenital chylothorax (CC) is a severe congenital disorder characterized by the collection of chyle in the pleural space. Recent case reports suggest that the use of octreotide in the treatment of CC may be useful. Objective: To evaluate the effect of octreotide on pleural effusions in CC. Methods: Hospital records of 7 patients with a CC, who were admitted to the Neonatal Intensive Care Unit of the Radboud University Nijmegen Medical Centre between 2006 and 2010 and were treated with octreotide, were retrospectively evaluated. Results: There was no clear and consistent effect of octreotide treatment on pleural effusions. Pleural effusions eventually decreased in all patients after reaching a dose of 5–6 µg/kg/min, but this could also reflect the natural history of CC. Out of 7 patients, 4 were diagnosed with persistent pulmonary hypertension of the newborn. No other known side effects of octreotide were found. There was a mortality rate of 30%. Conclusions: No clear and consistent effect of octreotide was identified. Pulmonary hypertension was a common problem in this patient group. It is not clear whether or not this was caused or maintained by octreotide treatment. A randomized controlled trial is needed to investigate the safety and usefulness of octreotide. Until then, clinicians should be careful in using octreotide, especially when persistent pulmonary hypertension is present.

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Section: Discussioncontrasting

confidence: 77%

Is Octreotide Treatment Useful in Patients with Congenital Chylothorax?

2011

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“…Recently published methods include describing CNV staining on FA relative to the size of optic nerve head (Sickenberg et al, 1999), by measuring diameter of CNV lesion along an axis (Criswell et al, 2008), by assessing lesion size based on the presence or absence of leakage (Dobi et al, 1989; Husain et al, 1999; Kanai et al, 2000; Obana et al, 2000; Tobe et al, 1998; Zacks et al, 2002), by using a qualitative grading method (Nishiwaki et al, 2002; Qu et al, 2009;Wang et al, 2007), and by measuring the CNV staining perimeter using imaging software (Funakoshi et al, 2006). None of these methods have been validated and many of them are arguably unable to detect small, but significant, changes in CNV lesion size due to their subjective and categorical (mild, moderate, severe) nature.…”

Section: Discussionmentioning

confidence: 99%

“…However, results vary considerably depending on which technique is used to quantify the CNV lesions, making it difficult to compare results among the above referenced studies. For instance, some methods are unable to detect small, but significant, changes in CNV lesions due to their subjective and categorical nature, such as classifying lesions as mild, moderate, severe or based on the presence or absence of leakage (Dobi et al, 1989; Husain et al, 1999; Kanai et al, 2000; Nishiwaki et al, 2002; Obana et al, 2000; Qu et al, 2009; Tobe et al, 1998; Wang et al, 2007; Zacks et al, 2002). Therefore, the purpose of this study is to develop new and compare existing methods of analyzing laser-induced CNV, on both choroidal mounts and FAs, to determine their validity and reliability in order to make recommendations that may improve the consistency of CNV reporting.…”

Section: Introductionmentioning

confidence: 99%

Improved assessment of laser-induced choroidal neovascularization

Toma

Barnett

Penn

et al. 2010

Microvascular Research

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The primary objective of this study was to develop and evaluate new methods of analyzing laser-induced choroidal neovascularization (CNV), in order to make recommendations for improving the reporting of experimental CNV in the literature. Six laser burns of sufficient power to rupture Bruch's membrane were concentrically placed in each eye of 18 adult Norway rats. Eyes received intravitreal injections of either triamcinolone acetonide, ketorolac, or balanced salt solution (BSS). Fluorescein angiography (FA) was performed 2 and 3 weeks after injection, followed by choroidal flat mount preparation. Vascular leakage on FAs and vascular budding on choroidal mounts were quantified by measuring either the cross-sectional area of each CNV lesion contained within the best-fitting polygon using Adobe Photoshop (Lasso Technique or Quick Selection Technique), or the area of bright pixels within a lesion using Image-Pro Plus. On choroidal mounts, the Lasso Technique and Image-Pro Plus detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while the Quick Selection Technique did not (Lasso Technique, 0.78 and 0.64; Image-Pro Plus, 0.77 and 0.65). On FA, the Lasso Technique and Quick Selection Technique detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while Image-Pro Plus did not (Lasso Tool, 0.81 and 0.54; Quick Selection Tool, 0.76 and 0.57). Choroidal mounts and FA are both valuable for imaging experimental CNV. Adobe Photoshop and Image-Pro Plus are both able to detect subtle differences in CNV lesion size, when images are not manipulated. The combination of choroidal mounts and FA provides a more comprehensive assessment of CNV anatomy and physiology.

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“…Studies showed that the formation of subretinal neovascularization arising from the choriocapillaris reaches maximal approximately 14 days post-laser induction [22][23][24] . In the present study, similar laser parameters to those in the previous studies were adopted, and the changes of CNV lesions and some hypoxia-regulated genes were detected on day 14 of rat CNV model after laser injury.…”

Section: Discussionmentioning

confidence: 99%

Blockade of the sonic hedgehog signalling pathway inhibits choroidal neovascularization in a laser-induced rat model

Zhang

et al. 2010

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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Sonic hedgehog (Shh) signaling has recently been shown to be involved in the pathological angiogenesis in response to tissue hypoxia and ischemic injury. Hypoxia/ischemia is considered to play an important role in the development of choroidal neovascularization (CNV). This study was aimed to examine the effect of blockade of the Shh signaling pathway on CNV and the underlying mechanism. A total of 64 male Brown-Norway (BN) rats were used in this study. One eye of each rat underwent laser photocoagulation. The other eye served as normal control. After the laser treatment, the 64 rats were divided into four groups (n=16 in each group): Blank control group, in which no intravitreal administration was given; cyclopamine group, recombinant Shh N-terminals protein (rShh) group and phosphate-buffered saline (PBS) group, in which cyclopamine (a Shh inhibitor), rShh (a Shh activator) and PBS were intravitreally injected into the laser-treated eyes respectively every other day for a total of four intravitreal injections immediately after the laser treatment. Fourteen days after the intravitreal administration, the changes of CNV-related variables, including positive CNV lesion percentage, CNV membrane area and CNV membrane thickness, were evaluated by fluorescein angiography, indocyanine green angiography and pathological examinations. The mRNA and protein expression of PTCH1, Gli1, HIF-1(α), VEGF and DLL4 in each group on 14 days of CNV model was detected by real-time quantitative PCR and western blot analysis, and the relationship between the Shh cascade and the HIF-1(α)-VEGF-DLL4 cascade in CNV was analyzed. The results showed that the CNV membrane area and the CNV membrane thickness were decreased by 62.5% and 41.9% in the cyclopamine group and increased by 85.7% and 64.3% in the rShh group in comparison to those in the blank control group (P<0.01 for each). There was no significant difference in the CNV membrane area and thickness between the blank control group and PBS group (P=0.102 and P=0.063, respectively). Real-time quantitative PCR revealed a 5.23-, 4.14-, 2.97-, 2.78- and 2.39-fold up-regulation of the mRNA expression of PTCH1, Gli1, HIF-1(α), VEGF and DLL4 genes in the laser-treated eyes compared with the normal control eyes in the control group. In the cyclopamine group, the mRNA and protein expression of Gli1, HIF-1(α), VEGF and DLL4 was significantly down-regulated (P<0.05 for each) while the expression of PTCH1 showed no significant changes at the mRNA (P=0.293) and protein level (P=0.304). The mRNA expression and protein expression (P=0.001 and P=0.021, respectively) of PTCH1, Gli1, HIF-1(α), VEGF and DLL4 was significantly increased in the rShh group when compared with the control group. The expression level of these genes was related to the severity of the CNV. It was concluded that intravitreal administration of cyclopamine can effectively inhibit the formation of laser-induced experimental CNV by down-regulating the expression of the HIF-1(α)-VEGF-DLL4 cascade in CNV. The Shh signaling pathway as an ...

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Octreotide Inhibits Choroidal Neovascularization in Rats

Cited by 9 publications

References 76 publications

Is Octreotide Treatment Useful in Patients with Congenital Chylothorax?

Is Octreotide Treatment Useful in Patients with Congenital Chylothorax?

Improved assessment of laser-induced choroidal neovascularization

Blockade of the sonic hedgehog signalling pathway inhibits choroidal neovascularization in a laser-induced rat model

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