Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate

Tolentino, Michael J.; McLeod, D. Scott; Taomoto, Makoto; Otsuji, Tsuyoshi; Adamis, Anthony P.; Lutty, Gerard A.

doi:10.1016/s0002-9394(01)01381-2

Cited by 226 publications

(131 citation statements)

References 24 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…42,43 Repeated injections of high concentrations of VEGF in eyes of nondiabetic monkeys provoke retinal changes that resemble those observed in the early stages of DR, including vascular tortuosity and microaneurysms. 44,45 Clinical trials using anti-VEGF therapies are showing promising results against advanced stages of DR. 46,47 Thus, without excluding the activation of other transduction pathways associated with retinal IPC, such as adenosine, K ATP channels, protein kinase C, 12,48 -49 and NO, 50 among others, and based on the fact that ischemia pulses abrogated the increase in VEGF, it is tempting to speculate that the induction of ischemic conditioning could behave as an anti-VEGF therapy. In fact, it was shown that injection of VEGF into healthy eyes of animals can induce diabetes-associated ocular diseases.…”

Section: Discussionmentioning

confidence: 99%

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Fernandez

Sande

Chianelli

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Diabetic retinopathy is a leading cause of acquired blindness. Available treatments are not very effective. We investigated the effect of a weekly application of retinal ischemia pulses (ischemic conditioning) on retinal damage induced by experimental diabetes. Diabetes was induced by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 minutes; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, whereas the contralateral eye was submitted to a sham procedure. Diabetic retinopathy was evaluated in terms of i) retinal function (electroretinogram and oscillatory potentials), ii) integrity of blood-retinal barrier (by albumin-Evans blue complex leakage and astrocyte glial fibrillary acidic protein IHC), iii) optical and electron microscopy histopathologic studies, and iv) vascular endothelial growth factor levels (using Western blot analysis and IHC). Brief ischemia pulses significantly preserved electroretinogram a-and b-wave and oscillatory potentials, avoided albumin-Evans blue leakage, prevented the decrease in astrocyte glial fibrillary acidic protein levels, reduced the appearance of retinal edemas, and prevented the increase in vascular endothelial growth factor levels induced by experimental diabetes. When the application of ischemia pulses started 6 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies for diabetic retinopathy treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Fernandez

Sande

Chianelli

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…In PDR, the growth of new vessels from the retina or optic nerve, is thought to occur as a result of vascular endothelial grow factor (VEGF) release into the vitreous cavity as a response to ischaemia. [2][3][4] Because VEGF has been shown to play a major role in retinal neovascularization (RN), 2,3 although other factors may be involved as well, 5,6 anti-VEGF treatments have been hypothesized as an alternative adjunctive treatment for RN. 7,8 Bevacizumab (Avastin TM Genentech Inc., San Francisco, CA, USA) is a complete full-length humanized antibody that binds to all subtypes of VEGF and is successfully used in tumour therapy as a systemic drug.…”

Section: Introductionmentioning

confidence: 99%

Intravitreal bevacizumab (avastin) for proliferative diabetic retinopathy: 6-months follow-up

Arévalo¹,

Sánchez³

et al. 2007

Eye

117

101

View full text Add to dashboard Cite

Aims To study the effects of intravitreal bevacizumab (Avastin) on retinal neovascularization (RN) in patients with proliferative diabetic retinopathy (PDR). Methods Retrospective study of patients with RN due to PDR who were treated with at least one intravitreal injection of 1.25 or 2.5 mg of bevacizumab. Patients underwent ETDRS best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at baseline and follow-up visits.Results Forty-four eyes of 33 patients with PDR and a mean age of 57.2-years (range: 23-82 years) participated in the study. Thirty-three eyes (75%) had previous panretinal photocoagulation (PRP). Twenty-seven eyes (61.4%) showed total regression of RN on fundus examination with absence of fluorescein leakage, 15 eyes (34.1%) demonstrated partial regression of RN on fundus examination and FA. Follow-up had a mean of 28.4 weeks (range from 24 to 40 weeks). BCVA and OCT demonstrated improvement (Po0.0001). Three eyes without previous PRP ('naive' eyes) and with vitreous haemorrhage have avoided vitreo-retinal surgery. One eye (2.2%) had PDR progression to tractional retinal detachment requiring vitrectomy, and one eye (2.2%) had vitreous haemorrhage with increased intraocular pressure (ghost cell glaucoma). No systemic adverse events were observed. Conclusions Intravitreal bevacizumab resulted in marked regression of RN in patients with PDR and previous PRP, and rapid resolution of vitreous haemorrhage in three naive eyes. Six-months results of intravitreal bevacizumab at doses of 1.25 or 2.5 mg in patients with PDR do not reveal any safety concerns.

show abstract

“…Uma única injeção intravítrea de VEGF em olhos de primatas leva à neovascularização iriana, retiniana e pré-retiniana (15,16,33) . Em outro estudo, observou-se que a razão VEGF 164 / VEGF 120 na retina de ratos com neovascularização retiniana induzida por isquemia era de 25.3 + 8.7, enFigura 1: A família de fatores de crescimento derivados do endotélio (VEGF) e seus receptores (VEGFR) encontrados nas células endoteliais vasculares e linfáticas; MMP9 = matrix metaloproteinase (9) Antiangiogênicos no glaucoma Rev Bras Oftalmol.…”

Section: Elevação Dos Níveis De Vegf Induz Neovascularização Ocularunclassified

“…Diversos estudos estabeleceram claramente que o bloqueio do VEGF pode inibir a neovascularização da íris (17) , coróide (19) , córnea (35) e retina (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) . Uma pesquisa experimental com primatas demonstrou que a injeção intravítrea de um anticorpo monoclonal antiVEGF previne a formação de neovasos de íris em um modelo de isquemia retiniana, após oclusão venosa induzida com laser (17) .…”

Section: Inativação Do Vegf Impede a Neovascularização Ocularunclassified

Antiangiogênicos no glaucoma

Lucena¹,

Yamane²

2008

Rev. bras.oftalmol.

View full text Add to dashboard Cite

RESUMOA angiogênese é um processo complexo que resulta na formação de novos vasos sangüíneos. Ocorre tanto em situações fisiológicas quanto patológicas e está envolvida com várias patologias oculares. Dentre os mediadores químicos da angiogênese, o fator de crescimento do endotélio vascular (VEGF) é reconhecido como um dos mais importantes. Nos últimos anos, agentes antiVEGF foram introduzidos para o tratamento de neovascularizações do segmento posterior com resultados muito positivos. Alguns autores demonstraram benefícios do uso dessas substâncias no controle do glaucoma em situações específicas.

show abstract

Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate

Cited by 226 publications

References 24 publications

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Intravitreal bevacizumab (avastin) for proliferative diabetic retinopathy: 6-months follow-up

Antiangiogênicos no glaucoma

Contact Info

Product

Resources

About