Antiangiogenic Therapy for Ischemic Retinopathies

Al-Latayfeh, Motasem; Silva, Paolo S.; Sun, Jennifer K.; Aiello, Lloyd Paul

doi:10.1101/cshperspect.a006411

Cited by 61 publications

(48 citation statements)

References 129 publications

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“…Our findings suggest that AOSLO imaging ca provide complementary information because fluid accumulation is readily visualized as darkening of the image, presumably due to increased intraretinal scatter, and hard exudates even of only a few microns in diameter are readily detected. Improvements in detection and quantification are desirable because while anti-VEGF and other anti-inflammatory therapies are successful, there remains a wide range in the success for specific patients and over time for these interventional treatments [48,49]. A better method of monitoring the effects of treatment may be helpful.…”

Section: Discussionmentioning

confidence: 99%

In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy

Burns

Elsner

Chui

et al. 2014

Biomed. Opt. Express

118

136

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Abstract:We used a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) to image the retina of subjects with nonproliferative diabetic retinopathy (NPDR). To improve visualization of different retinal features, the size and alignment of the confocal aperture were varied. The inner retinal layers contained clearly visualized retinal vessels. In diabetic subjects there was extensive capillary remodeling despite the subjects having only mild or moderate NPDR. Details of the retinal microvasculature were readily imaged with a larger confocal aperture. Hard exudates were observed with the AOSLO in all imaging modes. Photoreceptor layer images showed regions of bright cones and dark areas, corresponding in location to overlying vascular abnormalities and retinal edema. Clinically undetected intraretinal vessel remodeling and varying blood flow patterns were found. Perifoveal capillary diameters were larger in the diabetic subjects (p<0.01), and small arteriolar walls were thickened, based on wall to lumen measurements (p<.05). The results suggest that existing clinical classifications based on lower magnification clinical assessment may not adequately measure key vascular differences among individuals with NPDR.

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Section: Discussionmentioning

confidence: 99%

In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy

Burns

Elsner

Chui

et al. 2014

Biomed. Opt. Express

118

136

View full text Add to dashboard Cite

show abstract

“…VEGF-A is a main factor for physiological and pathological angiogenesis [4]. It is a heparin-binding homodimeric glycoprotein of 36-46 kDa weight [11, 12]. It acts via VEGFR-1 (Flt1) and VEGFR-2 (KDR) receptors.…”

Section: Introductionmentioning

confidence: 99%

“…It acts via VEGFR-1 (Flt1) and VEGFR-2 (KDR) receptors. The effects of their interactions are: stimulation of endothelial cells, migration of macrophages, increased vascular permeability, and a retinal blood barrier breakdown [4, 11]. Stimulation of VEGFR-1 (Flt1) enhances inflammatory cell (macrophages) attraction and migration [4].…”

Section: Introductionmentioning

confidence: 99%

“…The gene of human VEGF is composed of eight exons and seven introns between them [5, 11]. Due to alternative splicing of encoding VEGF-gene there are several isoforms of VEGF A: VEGF-A121, VEGF-A145, VEGF-A165, VEGF-A189, and VEGF-A206, which are classified by the number of amino acids [2–4, 11, 16, 17].…”

Section: Introductionmentioning

confidence: 99%

“…Due to alternative splicing of encoding VEGF-gene there are several isoforms of VEGF A: VEGF-A121, VEGF-A145, VEGF-A165, VEGF-A189, and VEGF-A206, which are classified by the number of amino acids [2–4, 11, 16, 17]. Among them VEGF-A165 is the most potent and the most abundant one [4, 11, 18]. It acts by binding to both VEGFR-1 and VEGFR-2, and it induces angiogenesis, cell migration, and vascular permeability [4].…”

Section: Introductionmentioning

confidence: 99%

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The era of anti-vascular endothelial growth factor (VEGF) drugs in ophthalmology, VEGF and anti-VEGF therapy

Pożarowska

Pożarowski

2016

cejoi

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Angiogenesis is a clue process for tissue development and function, both in normal and pathological conditions. This process is regulated by multiple molecular systems. One of the most potent is vascular endothelial growth factor (VEGF) and its receptor (VEGFR) system. Members of this family are involved in new vessel formation in embryogenesis and maturation, as well as in reparative or pathological reactions in later stages. They play a substantial role in regeneration, inflammation, wound healing, as well as in cancer pathology. Nowadays it is possible to modulate VEGF-VEGFR interactions in many pathological conditions using anti-VEGF therapy. This therapy has already achieved a grounded position in the management of rheumatological disorders, tumour progression, and metastasis. Such drugs as bevacizumab, ranibizumab, aflibercept, and pegaptanib have also proven to be very effective in the treatment of several ocular diseases, such as age-related macular degeneration (AMD), macular oedema, or proliferative retinopathies and iris neovascularisation. The indications for the application of this therapy in ophthalmology are becoming wider and wider. It may also be used for corneal pathologies and in anti-glaucoma procedures.

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In vitro and ex vivo retina angiogenesis assays

et al. 2013

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Pathological angiogenesis of the retina is a key component of irreversible causes of blindness, as observed in proliferative diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity. Seminal studies in the early 1980 s about the angiogenic activity exerted by mammalian retinal tissue extracts on the chick embryo chorioallantoic membrane and the later discovery of vascular endothelial growth factor (VEGF) accumulation in eyes of patients with diabetic retinopathy paved the way for the development of anti-angiogenic VEGF blockers for the treatment of retinal neovascularization. Since then, numerous preclinical and clinical studies about diabetic retinopathy and other retinal disorders have opened new lines of angiogenesis inquiry, indicating that limitations to anti-VEGF therapies may exist. Moreover, the production of growth factors other than VEGF may affect the response to anti-VEGF approaches. Thus, experimental models of retinal angiogenesis remain crucial for investigating novel anti-angiogenic therapies and bringing them to patients. To this aim, in vitro and ex vivo angiogenesis assays may be suitable for a rapid screening of potential anti-angiogenic molecules before in vivo validation of the putative lead compounds. This review focuses on the different in vitro and ex vivo angiogenesis assays that have been developed over the years based on the isolation of endothelial cells from the retina of various animal species and ex vivo cultures of neonatal and adult retina explants. Also, recent observations have shown that eye neovascularization in zebrafish (Danio rerio) embryos, an in vivo animal platform experimentally analogous to in vitro/ex vivo models, may represent a novel target for the identification of angiogenesis inhibitors. When compared to in vivo assays, in vitro and ex vivo models of retina neovascularization, including zebrafish embryo, may represent cost-effective and rapid tools for the screening of novel anti-angiogenic therapeutics.

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Antiangiogenic Therapy for Ischemic Retinopathies

Cited by 61 publications

References 129 publications

In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy

In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy

The era of anti-vascular endothelial growth factor (VEGF) drugs in ophthalmology, VEGF and anti-VEGF therapy

In vitro and ex vivo retina angiogenesis assays

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