Current therapeutic developments in atrophic age-related macular degeneration

Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

doi:10.1136/bjophthalmol-2015-306972

Cited by 77 publications

(53 citation statements)

References 70 publications

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“…This finding suggests that the pathogenesis of dry AMD is different from hereditary macular degeneration, such as Stargardt’s disease, and is not associated with a diffuse retinal dysfunction of the macula. Focal choroidal ischemia and structural changes in Bruch’s membrane leading to focal abnormalities in the RPE and photoreceptors can be considered in the pathogenesis of dry AMD (Hanus et al, 2016). …”

Section: Pathogenesis and Remodeling Of The Retina In Diseasementioning

confidence: 99%

Advances in bone marrow stem cell therapy for retinal dysfunction

Park

Moisseiev

Bauer

et al. 2017

Progress in Retinal and Eye Research

103

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The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy.

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Section: Pathogenesis and Remodeling Of The Retina In Diseasementioning

confidence: 99%

Advances in bone marrow stem cell therapy for retinal dysfunction

Park

Moisseiev

Bauer

et al. 2017

Progress in Retinal and Eye Research

103

View full text Add to dashboard Cite

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“…Given the direct involvement of A2E in the pathology, several strategies have been considered for designing treatments, either by preventing the formation/accumulation of this molecule, or by counteracting/reducing its deleterious effects [24,25,26,27,28]. Such attempts include (list not exhaustive):…”

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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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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“…Continuous light exposure increases oxidative stress [14,23] and is a major stimulator of retinal diseases [15], particularly dry AMD [24]. The extent of retinal degeneration depends on the light in- tensity and duration of light exposure [25].…”

Section: Discussionmentioning

confidence: 99%