Targeting neovascularization in ischemic retinopathy: recent advances

Abstract

Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities.

Blockade of TREM-1 prevents vitreoretinal neovascularization in mice with oxygen-induced retinopathy

“…In premature infants, normal retinal vascular development is interrupted resulting in retinal ischemia and invasion of the vitreous by abnormal neovessels. In addition, vitreoretinal neovascularization can promote traction retinal detachment, leading to blindness [5]. In the United States, 14,000–16,000 premature infants are affected by ROP annually [6,7].…”

Caspase-8 Modulates Angiogenesis By Regulating A Cell Death Independent Pathway In Endothelial Cells

“…In many pathological conditions such as ROP, proliferative diabetic retinopathy (PDR) and retina vein occlusion (RVO), among others, pathological retina neovascularization following tissue hypoxia is characterized by excessive extra-retinal neovascular tufts (50,68). In fact, it is the aberrant neovascularization in these patients that causes the biggest clinical challenge (blindness), rather than vessel regression itself (68).…”

“…In many pathological conditions such as ROP, proliferative diabetic retinopathy (PDR) and retina vein occlusion (RVO), among others, pathological retina neovascularization following tissue hypoxia is characterized by excessive extra-retinal neovascular tufts (50,68). In fact, it is the aberrant neovascularization in these patients that causes the biggest clinical challenge (blindness), rather than vessel regression itself (68). Here, by applying a model of oxygen-induced retinopathy (OIR), resembling ROP and producing neovascular lesions resembling those of PDR or RVO, we describe that Casp-8 is mechanistically involved in the pathophysiology of ocular neovascular diseases, Indeed, Casp-8 ECko mice, were Casp-8 was deleted in ECs just during the neovascularization phase, presented reduced aberrant vascular tufts.…”

Targeting Intramembrane Protein–Protein Interactions: Novel Therapeutic Strategy of Millions Years Old

“…In premature infants, normal retinal vascular development is interrupted resulting in retinal ischemia and invasion of the vitreous by abnormal neovessels. In addition, vitreoretinal neovascularization can promote traction retinal detachment, leading to blindness (Al-Shabrawey et al, 2013). In the United States, 14,000-16,000 premature infants are affected by ROP annually and about 4.1 million adults over 40 years have DR (Bashinsky, 2017;Hartnett, 2017).…”