Abstract
Many neurodegenerative retinal diseases are treated with monoclonal antibodies (mAb) delivered by invasive intravitreal injection (IVT). In Diabetic Retinopathy there is a scarcity of effective agents that can be delivered using non-invasive methods, and there are significant challenges in the validation of novel therapeutic targets. ProNGF represents a potential novel target, and IVT administration of a function-blocking anti-proNGF mAb is therapeutic in a mouse model of DR. We therefore compared invasive IVT to less invasive systemic intravenous (IV) and local subconjunctival (SCJ) administration, for therapy of Diabetic Retinopathy. The IV and SCJ routes are safe, afford sustained pharmacokinetics and tissue penetration of anti-proNGF mAb, and result in long–term therapeutic efficacy that blocks retinal inflammation, edema, and neuronal death. SCJ may be a more convenient and less-invasive approach for ophthalmic use and may enable reduced frequency of intervention for the treatment of retinal pathologies.
Highlights
The delivery of drugs to the posterior segment of the eye to treat retinopathies and inflammation can be achieved by direct intravitreal injection (IVT), and in some cases by subconjunctival injection (SCJ), or via systemic intravenous injection (IV)
The up-regulated α2M and TNFα mRNAs were significantly normalized in diabetic animals treated with anti-proNGF monoclonal antibodies (mAb) delivered by either IV or SCJ (p
Topical and intravitreal administration of drugs are used for different eye pathologies
Summary
The delivery of drugs to the posterior segment of the eye to treat retinopathies and inflammation can be achieved by direct intravitreal injection (IVT), and in some cases by subconjunctival injection (SCJ), or via systemic intravenous injection (IV). This manuscript examines the potential value of inhibiting proNGF, the ligand for the p75NTR receptor, as a therapeutic approach for Diabetic Retinopathy (DR). We compare the therapeutic efficacy of IVT, IV and SCJ administration of a function–blocking monoclonal antibody (mAb) against proNGF. DR, the leading cause of blindness, is characterized by early retinal neurovascular dysfunction [1,2,3] followed by hypoxia and VEGF–mediated pathological angiogenesis
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