Endocrine Abstracts (2008) 15 S19

Hypoxia, angiogenesis and proliferative diabetic retinopathy

Paul Bishop

University of Manchester, Manchester, UK.

Proliferative diabetic retinopathy is a major complication of diabetes that is characterised by the growth of new blood vessels from the pre-existing retinal circulation into the vitreous humour, i.e. it is a process of angiogenesis. The initial insult is capillary loss in the mid-peripheral and peripheral retina. The resultant retinal hypoxia stimulates the production of pro-angiogenic growth factors, with vascular endothelial growth factor and the growth hormone/insulin-like growth hormone-1 axis being implicated in the resultant angiogenic response. The ischaemic retina is unable to support revascularisation for reasons that are poorly understood. Instead the collagen fibrillar network of the vitreous humour supports a process of intussusceptive angiogenesis and new blood vessels grow into the vitreous cavity (preretinal neovascularisation). As well as providing a mechanical support for growth, collagen fibrils provide critical signalling for angiogenesis through integrins, including α2β1 integrin, on endothelial cell surfaces. Visual loss is caused by the new blood vessels in the vitreous humour bleeding, and by the contraction of scar tissue associated with these blood vessels leading to tractional retinal detachment.

The vitreous collagen fibrils are coated with an extracellular matrix molecule called opticin. We have shown that opticin inhibits preretinal neovascularisation in a dose-dependent manner. Opticin interacts with the α2β1 integrin on endothelial cells. Whilst this same integrin when it binds collagen promotes angiogenesis, the interaction with opticin blocks stimulatory signals or may indeed result in outside-to-inside signalling that inhibits angiogenesis. Therefore the levels of opticin in the vitreous cavity may reflect a diabetic patient’s propensity to develop proliferative retinopathy.

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