Topical cyclodextrin reduces amyloid beta and inflammation improving retinal function in ageing mice

The accumulation of N-retinylidene-N-retinylethanolamine (A2E, a toxic by-product of the visual pigment cycle) in the retinal pigment epithelium (RPE) is a major cause of visual impairment in the elderly. Photooxidation of A2E results in retinal pigment epithelium degeneration followed by that of associated photoreceptors. Present treatments rely on nutrient supplementation with antioxidants. 9’-cis-Norbixin (a natural diapocarotenoid, 97% purity) was prepared from Bixa orellana seeds. It was first evaluated in primary cultures of porcine retinal pigment epithelium cells challenged with A2E and illuminated with blue light, and it provided an improved photo-protection as compared with lutein or zeaxanthin. In Abca4-/- Rdh8-/- mice (a model of dry AMD), intravitreally-injected norbixin maintained the electroretinogram and protected photoreceptors against light damage. In a standard rat blue-light model of photodamage, norbixin was at least equally as active as phenyl-N-tert-butylnitrone, a free radical spin-trap. Chronic experiments performed with Abca4-/- Rdh8-/- mice treated orally for 3 months with norbixin showed a reduced A2E accumulation in the retina. Norbixin appears promising for developing an oral treatment of macular degeneration. A drug candidate (BIO201) with 9’-cis-norbixin as the active principle ingredient is under development, and its potential will be assessed in a forthcoming clinical trial.

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“…promoting A2E removal by intravitreal injection of cyclodextrins [32,33] or by promoting enzymatic degradation of A2E [34,35];…”

Section: Introductionmentioning

confidence: 99%

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

et al. 2016

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“…Previously, preclinical attempts at retinal drug delivery by topical administration have been reported. They were based on several daily applications over prolonged periods [37,38]. Other groups used transscleral iontophoresis [39] to improve the intraocular delivery of topically administered drugs.…”

Section: Discussionmentioning

confidence: 99%

Magnetically Assisted Drug Delivery of Topical Eye Drops Maintains Retinal Function In Vivo in Mice

et al. 2021

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Barded-Biedl syndrome (BBS) is a rare genetic disorder with an unmet medical need for retinal degeneration. Small-molecule drugs were previously identified to slow down the apoptosis of photoreceptors in BBS mouse models. Clinical translation was not practical due to the necessity of repetitive invasive intravitreal injections for pediatric populations. Non-invasive methods of retinal drug targeting are a prerequisite for acceptable adaptation to the targeted pediatric patient population. Here, we present the development and functional testing of a non-invasive, topical, magnetically assisted delivery system, harnessing the ability of magnetic nanoparticles (MNPs) to cargo two drugs (guanabenz and valproic acid) with anti-unfolded protein response (UPR) properties towards the retina. Using magnetic resonance imaging (MRI), we showed the MNPs’ presence in the retina of Bbs wild-type mice, and their photoreceptor localization was validated using transmission electron microscopy (TEM). Subsequent electroretinogram recordings (ERGs) demonstrated that we achieved beneficial biological effects with the magnetically assisted treatment translating the maintained light detection in Bbs−/− mice (KO). To our knowledge, this is the first demonstration of efficient magnetic drug targeting in the photoreceptors in vivo after topical administration. This non-invasive, needle-free technology expands the application of SMDs for the treatment of a vast spectrum of retinal degenerations and other ocular diseases.

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“…Kam et al applied 2-hydroxypropyl-β-cyclodextrin to an elderly mouse model, which significantly reduced Aβ by 65% and inflammation by 75% within three months. It is also applicable to CFH gene knockout mouse models [78]. Qian et al prepared a delivery system composed of graphene quantum dots (GQD) encapsulation, and supramolecular β-cyclodextrin that co-loaded Bevacizumabu and Rani Bizumabu.…”

Section: Cyclodextrinmentioning

confidence: 99%

Nanotechnology for Age-Related Macular Degeneration

Yang

Liu

et al. 2021

Pharmaceutics

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Age-related macular degeneration (AMD) is a degenerative eye disease that is the leading cause of irreversible vision loss in people 50 years and older. Today, the most common treatment for AMD involves repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, the existing expensive therapies not only cannot cure this disease, they also produce a variety of side effects. For example, the number of injections increases the cumulative risk of endophthalmitis and other complications. Today, a single intravitreal injection of gene therapy products can greatly reduce the burden of treatment and improve visual effects. In addition, the latest innovations in nanotherapy provide the best drug delivery alternative for the treatment of AMD. In this review, we discuss the development of nano-drug delivery systems and gene therapy strategies for AMD in recent years. In addition, we discuss some novel targeting strategies and the potential application of these delivery methods in the treatment of AMD. Finally, we also propose that the combination of CRISPR/Cas9 technology with a new non-viral delivery system may be promising as a therapeutic strategy for the treatment of AMD.

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Topical cyclodextrin reduces amyloid beta and inflammation improving retinal function in ageing mice

Cited by 21 publications

References 38 publications

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

Magnetically Assisted Drug Delivery of Topical Eye Drops Maintains Retinal Function In Vivo in Mice

Nanotechnology for Age-Related Macular Degeneration

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