Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions

Guimarães, Thales Antonio Cabral de; Varela, Malena Daich; Georgiou, Michalis; Michaelides, Michel

doi:10.1136/bjophthalmol-2020-318452

Cited by 101 publications

(68 citation statements)

References 75 publications

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“…Many potential interventions to prevent advanced AMD are currently being investigated. These include the administration of drugs or genetic therapies that modulate retinal complement activation, provide neurotrophic support to photoreceptors [ 109 ] and cell therapy to replenish the degenerate RPE/Bruch’s membrane [ 110 ]. Recent advances in our understanding of the mechanisms of retinal inflammation contributing to AMD highlight potential new avenues for therapeutic intervention in early and intermediate AMD.…”

Section: Discussionmentioning

confidence: 99%

Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration

Quinn

2021

Life

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Age-related macular degeneration (AMD) is a multifactorial retinal disorder that is a major global cause of severe visual impairment. The development of an effective therapy to treat geographic atrophy, the predominant form of AMD, remains elusive due to the incomplete understanding of its pathogenesis. Central to AMD diagnosis and pathology are the hallmark lipid and proteinaceous deposits, drusen and reticular pseudodrusen, that accumulate in the subretinal pigment epithelium and subretinal spaces, respectively. Age-related changes and environmental stressors, such as smoking and a high-fat diet, are believed to interact with the many genetic risk variants that have been identified in several major biochemical pathways, including lipoprotein metabolism and the complement system. The APOE gene, encoding apolipoprotein E (APOE), is a major genetic risk factor for AMD, with the APOE2 allele conferring increased risk and APOE4 conferring reduced risk, in comparison to the wildtype APOE3. Paradoxically, APOE4 is the main genetic risk factor in Alzheimer's disease, a disease with features of neuroinflammation and amyloid-beta deposition in common with AMD. The potential interactions of APOE with the complement system and amyloid-beta are discussed here to shed light on their roles in AMD pathogenesis, including in drusen biogenesis, immune cell activation and recruitment, and retinal inflammation.

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Section: Discussionmentioning

confidence: 99%

Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration

Quinn

2021

Life

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“…The role of VEGF in the pathophysiology of AMD converted the anti-VEGF agents into the gold standard therapy of the disease, especially in its wet form [ 266 ]. Nevertheless, antioxidant supplements based on multivitamins, omega-3, trace elements, and natural extracts are usually prescribed as an adjuvant treatment for preventing and slowing the progression of AMD.…”

Section: Treatmentmentioning

confidence: 99%

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

et al. 2021

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Most irreversible blindness observed with glaucoma and retina-related ocular diseases, including age-related macular degeneration and diabetic retinopathy, have their origin in the posterior segment of the eye, making their physiopathology both complex and interconnected. In addition to the age factor, these diseases share the same mechanism disorder based essentially on oxidative stress. In this context, the imbalance between the production of reactive oxygen species (ROS) mainly by mitochondria and their elimination by protective mechanisms leads to chronic inflammation. Oxidative stress and inflammation share a close pathophysiological process, appearing simultaneously and suggesting a relationship between both mechanisms. The biochemical end point of these two biological alarming systems is the release of different biomarkers that can be used in the diagnosis. Furthermore, oxidative stress, initiating in the vulnerable tissue of the posterior segment, is closely related to mitochondrial dysfunction, apoptosis, autophagy dysfunction, and inflammation, which are involved in each disease progression. In this review, we have analyzed (1) the oxidative stress and inflammatory processes in the back of the eye, (2) the importance of biomarkers, detected in systemic or ocular fluids, for the diagnosis of eye diseases based on recent studies, and (3) the treatment of posterior ocular diseases, based on long-term clinical studies.

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“…In another model of inhibition of oxidative stress, GPETAFLR, a lupin-originated octapeptide, was demonstrated to increase cell viability and improve GSH synthesis, while suppressing ROS generation in retinal pigment epithelium cells [ 28 ]. This finding suggests that consumption of lupin-rich diet will provide health benefits such as delaying the onset of AMD, a condition that has been shown to be associated with free radical attack on ocular tissues, compromising the blood-retinal barrier that results in initiation and progression of ADM [ 82 , 83 , 84 ]. Taken together, these reports on the antioxidant properties of LDPs strongly position LDPs as candidates for functional food developments for diseases with oxidative stress etiology.…”

Section: Biological Activities Of Ldpsmentioning

confidence: 99%

Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits

et al. 2021

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There is a renewed interest on the reliance of food-based bioactive compounds as sources of nutritive factors and health-beneficial chemical compounds. Among these food components, several proteins from foods have been shown to promote health and wellness as seen in proteins such as α/γ-conglutins from the seeds of Lupinus species (Lupin), a genus of leguminous plant that are widely used in traditional medicine for treating chronic diseases. Lupin-derived peptides (LDPs) are increasingly being explored and they have been shown to possess multifunctional health improving properties. This paper discusses the intestinal transport, bioavailability and biological activities of LDPs, focusing on molecular mechanisms of action as reported in in vitro, cell culture, animal and human studies. The potentials of several LDPs to demonstrate multitarget mechanism of regulation of glucose and lipid metabolism, chemo- and osteoprotective properties, and antioxidant and anti-inflammatory activities position LDPs as good candidates for nutraceutical development for the prevention and management of medical conditions whose etiology are multifactorial.

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Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions

Cited by 101 publications

References 75 publications

Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration

Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits

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