Normal Aging Involves Altered Expression of Growth Factors in the Rat Choroid

Steinle, Jena J.; Sharma, Sheena; Chin, Vannak C.

doi:10.1093/gerona/63.2.135

Cited by 18 publications

(17 citation statements)

References 33 publications

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“…As RPE is pivotal for maintaining the structure and function of the retina, the early alteration of RPE cells may be a key initiating factor for retinopathy development in OXYS rats and a cause of all subsequent pathological changes. Clinical and experimental data suggest that normal aging processes can lead to structural and blood flow changes that can predispose an individual to AMD, although advanced age does not inevitably cause AMD [27,28]. Thus our investigation has shown that particularly age-related changes of retinal ultrastructure in Wistar and OXYS rats are non-specific, generally speaking, but the age of onset and rate of retinopathy development differ sharply between these strains.…”

Section: Discussionmentioning

confidence: 64%

Alterations of retinal pigment epithelium cause AMD-like retinopathy in senescence-accelerated OXYS rats

Markovets

Saprunova

Zhdankina

et al. 2010

Aging

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Pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the world, remains poorly understood. This makes it necessary to create animal models for studying AMD pathogenesis and to design new therapeutic approaches. Here we showed that retinopathy in OXYS rats is similar to human AMD according to clinical signs, morphology, and vascular endothelium growth factor (VEGF) and pigment epithelium-derived factor (PEDF) genes expression. Clinical signs of retinopathy OXYS rats manifest by the age 3 months against the background of significantly reduced expression level of VEGF and PEDF genes due to the decline of the amount of retinal pigment epithelium (RPE) cells and alteration of choroidal microcirculation. The disruption in OXYS rats' retina starts at the age of 20 days and appears as reduce the area of RPE cells but does not affect their ultrastructure. Ultrastructural pathological alterations of RPE as well as develop forms of retinopathy are observed in OXYS rats from age 12 months and manifested as excessive accumulation of lipofuscin in RPE regions adjacent to the rod cells, whirling extentions of the basement membrane into the cytoplasm. These data suggest that primary cellular degenerative alterations in the RPE cells secondarily lead to choriocapillaris atrophy and results in complete loss of photoreceptor cells in the OXYS rats' retina by the age of 24 months.

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Section: Discussionmentioning

confidence: 64%

Alterations of retinal pigment epithelium cause AMD-like retinopathy in senescence-accelerated OXYS rats

Markovets

Saprunova

Zhdankina

et al. 2010

Aging

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“…PEDF levels are reduced in the skin [69] and retinal pigmented epithelium with age [70], but elevated in the kidney [71]; however, changes in PEDF protein levels in the joint with aging are not known. Future studies should explore the effect of aging on PEDF protein levels in the joint.…”

Section: Discussionmentioning

confidence: 99%

Pigment Epithelium-Derived Factor (PEDF) mediates cartilage matrix loss in an age-dependent manner under inflammatory conditions

Nakamura

Hollander

Uchimura

et al. 2017

BMC Musculoskelet Disord

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BackgroundInflammation is a major cause of cartilage destruction and leads to the imbalance of metabolic activities in the arthritic joint. Pigment epithelium-derived factor (PEDF) has been reported to have both pro- and anti-inflammatory activities in various cell types and to be upregulated in the arthritic joint, but its role in joint destruction is unclear. Our aim was to investigate the role of PEDF in cartilage degeneration under inflammatory conditions.MethodsPEDF was ectopically expressed in primary human articular chondrocytes, and catabolic gene expression and protein secretion in response to the pro-inflammatory cytokine interleukin 1 beta (IL-1β) were evaluated. Metatarsal bones from PEDF-deficient and wild type mice were cultured in the presence or absence of IL-1β. Cartilage matrix integrity and matrix metalloproteinases MMP-1, MMP-3, and MMP-13 were evaluated. PEDF-deficient and wild type mice were evaluated in the monosodium iodoacetate (MIA) inflammatory joint destruction animal model to determine the role of PEDF in inflammatory arthritis in vivo. Student’s t-tests and Mann–Whitney tests were employed where appropriate, for parametric and non-parametric data, respectively.ResultsWe showed that PEDF protein levels were higher in human osteoarthritis samples compared to normal samples. We demonstrated that ectopic PEDF expression in primary human articular chondrocytes exacerbated catabolic gene expression in the presence of IL-1β. In whole bone organ cultures, IL-1β induced MMP-1, MMP-3 and MMP-13 protein production, and caused significant cartilage matrix loss. Interestingly, Toluidine Blue staining showed that PEDF-deficient bones from 29 week old animals, but not 10 week old animals, had reduced matrix loss in response to IL-1β compared to their wild type counterparts. In addition, PEDF-deficiency in 29 week old animals preserved matrix integrity and protected against cell loss in the MIA joint destruction model in vivo.ConclusionWe conclude that PEDF exacerbates cartilage degeneration in an age-dependent manner under an inflammatory setting. This is the first study identifying a specific role for PEDF in joint inflammation and highlights the multi-faceted activities of PEDF.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-017-1410-y) contains supplementary material, which is available to authorized users.

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confidence: 99%

“…7 The production of neurotrophic and angiogenic factors secreted by the RPE shows age-related changes. 8,9 Recently, it has been shown that the RPE/choroid complex becomes immunoreactive with aging 10 ; this may be associated with chronic inflammation and abnormal immune responses under certain genetically susceptible backgrounds such as complement factor H mutation. The molecular mechanisms underlying these age-related changes are largely unknown.…”

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confidence: 99%