Fundamental differences in patterns of retinal ageing between primates and mice

Kam, Jaimie Hoh; Weinrich, Tobias W.; Shinhmar, Harpreet; Powner, Michael B.; Roberts, Nicholas W.; Aboelnour, Asmaa; Jeffery, Glen

doi:10.1038/s41598-019-49121-0

Cited by 19 publications

(26 citation statements)

References 71 publications

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“…Eyes were only retrieved after death. This was identical to Hoh Kam et al 2019 (Scienti c Reports 9:12574 32 . Hence no experiments were undertaken as tissues were harvested after death which is not a regulated procedure.…”

Section: Animals: Primatessupporting

confidence: 86%

The 3D Organisation of Mitochondria in Primate Photoreceptors

Hayes

Tracey‐White

Kam

et al. 2021

Preprint

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Vertebrate photoreceptors contain large numbers of closely-packed mitochondria which sustain the high metabolic demands of these cells. These mitochondria populations are dynamic and undergo fusion and fission events. This activity serves to maintain the population in a healthy state. In the event of mitochondrial damage, sub-domains, or indeed whole mitochondria, can be degraded and population homeostasis achieved. If this process is overwhelmed cell death may result. Death of photoreceptors contributes to loss of vision in aging individuals and is associated with many eye diseases. In this study we used serial block face scanning electron microscopy of adult (Macaca fascicularis) retinae to examine the 3D structure of mitochondria in rod and cone photoreceptors. Healthy-looking photoreceptors contain mitochondria with a range of shapes which are associated with different regions of the cell. In some photoreceptors we observe mitochondrial swelling and other changes we associate with stress or degeneration of the cell. In both rods and cones we identify elongated domains of mitochondria with densely-packed normal cristae associated with photoreceptor ciliary rootlet bundles. We observe mitochondrial fission and mitochondrion fragments localised to these domains. Swollen mitochondria with few intact cristae are located towards the periphery of the photoreceptor inner-segment in rods, whilst they are found throughout the cell in cones. Swollen mitochondria exhibit sites on the mitochondrial inner membrane which have undergone complex invagination resulting in membranous, electron-dense aggregates. Membrane contact occurs between the mitochondrion and the photoreceptor plasma membrane in the vicinity of these aggregates, and a series of subsequent membrane fusions results in expulsion of the mitochondrial aggregate from the photoreceptor. These events are primarily associated with rods, likely reflecting the ageing mechanism in primates where many rods die but cones do not. Possible consequences of this atypical mitochondrial degradation are discussed.

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Section: Animals: Primatessupporting

confidence: 86%

The 3D Organisation of Mitochondria in Primate Photoreceptors

Hayes

Tracey‐White

Kam

et al. 2021

Preprint

Self Cite

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“…In addition, these analyses are fundamentally limited by the scarcity of human donor eyes in certain age groups. Animal and in vitro models have been used to attempt to address this limitation (Conn, 2006); however, the human retina has singular properties that render extrapolation from these systems difficult (Hussain et al, 2010;Kam et al, 2019). In this review, we harness the fact that local mass transport is partly determined by the morphology of cells and the specific geometry of their interface with other tissue components.…”

Section: From Geometry To Mass Transportmentioning

confidence: 99%

Variability in Retinal Neuron Populations and Associated Variations in Mass Transport Systems of the Retina in Health and Aging

Zouache

2022

Front. Aging Neurosci.

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Aging is associated with a broad range of visual impairments that can have dramatic consequences on the quality of life of those impacted. These changes are driven by a complex series of alterations affecting interactions between multiple cellular and extracellular elements. The resilience of many of these interactions may be key to minimal loss of visual function in aging; yet many of them remain poorly understood. In this review, we focus on the relation between retinal neurons and their respective mass transport systems. These metabolite delivery systems include the retinal vasculature, which lies within the inner portion of the retina, and the choroidal vasculature located externally to the retinal tissue. A framework for investigation is proposed and applied to identify the structures and processes determining retinal mass transport at the cellular and tissue levels. Spatial variability in the structure of the retina and changes observed in aging are then harnessed to explore the relation between variations in neuron populations and those seen among retinal metabolite delivery systems. Existing data demonstrate that the relation between inner retinal neurons and their mass transport systems is different in nature from that observed between the outer retina and choroid. The most prominent structural changes observed across the eye and in aging are seen in Bruch’s membrane, which forms a selective barrier to mass transfers at the interface between the choroidal vasculature and the outer retina.

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“…As rodents lack anatomical maculae, rodent models may not recapitulate all facets of AMD and translate to humans. Furthermore, fundamental differences in retinal aging between mice and primates have also been identified, with variation in Aβ deposition patterns over time [ 96 ]. Many Aβ-targeting therapies in AD perform well in rodents, only to fall short in human trials [ 97 ].…”

Section: Interactions Between Amyloid-β and Apolipoproteinsmentioning

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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Fundamental differences in patterns of retinal ageing between primates and mice

Cited by 19 publications

References 71 publications

The 3D Organisation of Mitochondria in Primate Photoreceptors

The 3D Organisation of Mitochondria in Primate Photoreceptors

Variability in Retinal Neuron Populations and Associated Variations in Mass Transport Systems of the Retina in Health and Aging

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

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