Computer-aided quantification of retinal neovascularization

Stahl, Andreas; Connor, Kip M.; Sapieha, Przemysław; Willett, Keirnan; Krah, Nathan M.; Dennison, R. J.; Chen, J.; Guerin, Karen I.; Smith, Lois E H

doi:10.1007/s10456-009-9155-3

Cited by 134 publications

(131 citation statements)

References 16 publications

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“…NV at P17 was quantitated by using an automated protocol. 15 Eya3 VEC-KO retinas had nearly 40% less NV than did control retinas ( Figure 3C). Interestingly, residual VO in the central avascular area was comparable in the control and Eya3…”

Section: Targeted Deletion Of Eya3 In Ecs Attenuates Nv In the Oxygenmentioning

confidence: 94%

The Eyes Absent Proteins in Developmental and Pathological Angiogenesis

Wang

Tadjuidje

Pandey

et al. 2016

The American Journal of Pathology

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Management of neoangiogenesis remains a high-value therapeutic goal. A recently uncovered association between the DNA damage repair pathway and pathological angiogenesis could open previously unexplored possibilities for intervention. An attractive and novel target is the Eyes absent (EYA) tyrosine phosphatase, which plays a critical role in the repair versus apoptosis decision after DNA damage. This study examines the role of EYA in the postnatal development of the retinal vasculature and under conditions of ischemia-reperfusion encountered in proliferative retinopathies. We find that the ability of the EYA proteins to promote endothelial cell (EC) migration contributes to a delay in postnatal development of the retinal vasculature when Eya3 is deleted specifically in ECs. By using genetic and chemical biology tools, we show that EYA contributes to pathological angiogenesis in a model of oxygen-induced retinopathy. Both in vivo and in vitro, loss of EYA tyrosine phosphatase activity leads to defective assembly of g-H2AX foci and thus to DNA damage repair in ECs under oxidative stress. These data reveal the potential utility of EYA tyrosine phosphatase inhibitors as therapeutic agents in inhibiting pathological neovascularization with a range of clinical applications. (Am J Pathol 2016, 186: 568e578; http:// dx

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Section: Targeted Deletion Of Eya3 In Ecs Attenuates Nv In the Oxygenmentioning

confidence: 94%

The Eyes Absent Proteins in Developmental and Pathological Angiogenesis

Wang

Tadjuidje

Pandey

et al. 2016

The American Journal of Pathology

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“…Neonatal mice with their nursing mother were exposed to 75% oxygen from P7-12 to induce retinopathy and killed at P17, followed by retinal dissection and staining overnight with fluorescent Griffonia simplicifolia isolectin B 4 (Invitrogen). Vaso-obliteration and neovascularization in OIR were quantified by using Adobe Photoshop and ImageJ (48). Quantification was performed with the identity of the samples masked, with n being the number of mice quantified.…”

Section: Methodsmentioning

confidence: 99%

Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

Liu

Sun

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.neovascularization | endothelial cells | microRNA | miR-150 | retinopathy

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“…At P17, mice were anesthetized, and retinas were dissected followed by either RNA isolation or fluoresceinated isolectin IB 4 (Griffonia simplicifolia) (Invitrogen, Carlsbad, CA, USA) staining to visualize vessels on whole-mount retinas. Areas of retinal vaso-obliteration and pathological neovascularization were quantified as a percentage of total retinal areas using Adobe Photoshop (Adobe Systems, San Jose, CA, USA) and ImageJ (National Institutes of Health, Bethesda, MD, USA) according to previous protocols (31). Sg/ Sg mice and WT mice were maintained within normal body weight range for OIR (5-7.5 g at P17) (32) through adjusting litter size.…”

Section: Oirmentioning

confidence: 99%

RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis

et al. 2017

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Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood. Here we showed that retinoic acid receptor-related orphan receptor a (RORa), a nuclear receptor and transcription factor, is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in a mouse model of oxygen-induced proliferative retinopathy. We found that genetic deficiency of RORa substantially induced Sema3e expression in retinopathy. Both RORa and SEMA3E were expressed in retinal ganglion cells. RORa directly bound to a specific ROR response element on the promoter of Sema3e and negatively regulated Sema3e promoter-driven luciferase expression. Suppression of Sema3e using adeno-associated virus 2 carrying short hairpin RNA targeting Sema3e promoted disoriented pathological neovascularization and partially abolished the inhibitory vascular effects of RORa deficiency in retinopathy. Our findings suggest that RORa is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in pathological retinal angiogenesis.-Sun, Y., Liu, C.-H., Wang, Z., Meng, S. S., Burnim, S. B., SanGiovanni, J. P., Kamenecka, T. M., Solt, L. A., Chen, J. RORa modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis. FASEB J. 31, 4492-4502 (2017). www.fasebj.org

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Computer-aided quantification of retinal neovascularization

Cited by 134 publications

References 16 publications

The Eyes Absent Proteins in Developmental and Pathological Angiogenesis

The Eyes Absent Proteins in Developmental and Pathological Angiogenesis

Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis

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