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Subspecialties Basic & Translational Research, Retina

Enter the Inflammasome

VEGF is something of a Jekyll and Hyde molecule, with both physiological as well as pathological functions (1). Although critical for vascular development, it’s also strongly linked to angiogenic retinal pathologies, such as wet AMD and diabetic macular edema. Intravitreal anti-VEGF injections are the gold standard for treating the choroidal neovascularization that’s associated with such diseases, and although they have transformed patients’ outcomes, they aren’t a panacea. In many cases, their efficacy does not last forever, and there is concern that VEGF inhibition in the retina may lead to thinning and atrophy of the choriocapillaris, photoreceptor degeneration, eventually causing damage to the retina – the complete opposite of the intended result.

Accordingly, researchers continue to seek a better therapy – but finding one may require a greater understanding of VEGF’s role in ocular pathologies, according to Alexander Marneros, of Massachusetts General Hospital. Marneros used a genetically modified mouse model which expresses VEGF-A at two-to-three times physiological levels, with VEGF expression found in the lens, retina and ciliary body, in order to study the protein’s role in AMD pathogenesis. “Identifying the downstream mechanisms by which VEGF-A influences the development of these diseases may lead to new therapies that don’t have the adverse effects of blocking VEGF-A itself,” he says.

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