Abstract
Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy.
Highlights
Neurotrophins (NTs) are known to promote neuronal survival and regeneration in both the central (CNS) and peripheral nervous system (PNS) [1]
We demonstrated that magnetic nanoparticles (MNPs) could be used to bypass the limitations related to the IVT injection of free proteins [21, 22]
For the synthesis of MNP–brain-derived neurotrophic factor (BDNF), we chemically linked the protein to MNPs
Summary
Neurotrophins (NTs) are known to promote neuronal survival and regeneration in both the central (CNS) and peripheral nervous system (PNS) [1]. Glaucoma is the most common, and is characterized by visual loss due to optic nerve dysfunction. The loss of retinal ganglion cells (RGCs) is a common feature of neuropathies, irrespectively of the aetiology of the disease. The nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of the NT family, which have been shown to prevent damage to GCL. NGF promotes the survival and recovery of retinal ganglion cells [3, 4]. It has been demonstrated that the injection of exogenous NGF protects retinal ganglion cells from degeneration and apoptosis in different experimental models of retinal detachment, diabetic retinopathy and glaucoma [5,6,7]. BDNF prevents the in vivo cell death of GCL induced by optic nerve lesions, providing therapeutic neuroprotection [12, 13]
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