Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration

Fehér, János; Kovács, Illés; Artico, Marco; Cavallotti, Carlo; Papale, A.; Gabrieli, C. Balacco

doi:10.1016/j.neurobiolaging.2005.05.012

Cited by 339 publications

(266 citation statements)

References 64 publications

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“…Mitochondrial ion channels are critically involved in apoptotic changes in mitochondria (42). In addition to the well-documented changes in mtDNA, our data suggest that alterations in mtMEM also play a crucial role in the development of mitochondrial dysfunctions in AMD and, possibly, in other age-related diseases (92). This has an immediate clinical relevance as shown by several in vitro and in vivo studies.…”

Section: Discussionsupporting

confidence: 65%

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis

Bianchi

Scarinci

Ripandelli

et al. 2012

International Journal of Molecular Medicine

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Abstract. Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

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Section: Discussionsupporting

confidence: 65%

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis

Bianchi

Scarinci

Ripandelli

et al. 2012

International Journal of Molecular Medicine

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“…Marked increase in the percentage of oversized mitochondria with structural abnormalities have been reported in several instances including in RPE cells of advance aged individuals with Fig. 9 increasing severity [42] of AMD at the synaptic terminals of old rats [75] and in other adverse conditions where cells are exposed to large amounts of free radicals over an extended period [76,77]. The speculation is that numeric loss of mitochondria is due, in part, to impaired duplicative capacity of these organelles and that a shift in size compensates for numbers to keep volume density and area involved in cellular respiration constant during the lifespan of the individual [70,[78][79][80].…”

Section: Discussionmentioning

confidence: 89%

“…Histological changes in mitochondrial morphology are evident in the RPE at the earliest stages of AMD and precede vision loss, even though the disease has been primarily associated with photoreceptor damage [38][39][40][41][42].…”

Section: Introductionmentioning

confidence: 99%

Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress

Burke

et al. 2010

j ocul biol dis inform

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Impairment of mitochondria function and cellular antioxidant systems are linked to aging and neurodegenerative diseases. In the eye, the retinal pigment epithelium (RPE) is exposed to a highly oxidative environment that contributes to age-related visual dysfunction. Here, we examined changes in mitochondrial function in human RPE cells and sensitivity to oxidative stress with increased chronological age. Primary RPE cells from young (9-20)-, mid-age (48-60)-, and >60 (62-76)-year-old donors were grown to confluency and examined by electron microscopy and flow cytometry using several mitochondrial functional assessment tools. Susceptibility of RPE cells to H 2 O 2 toxicity was determined by lactate dehydrogenase and cytochrome c release, as well as propidium iodide staining. Reactive oxygen species, cytoplasmic Ca 2+ [Ca 2+ ] c , and mitochondrial Ca 2+ [Ca 2+ ] m levels were measured using 2′,7′-dichlorodihydrofluorescein diacetate, fluo-3/AM, and Rhod-2/AM, respectively, adenosine triphosphate (ATP) levels were measured by a luciferin/luciferase-based assay and mitochondrial membrane potential (ΔΨm) estimated using 5,5′,6,6′-tetrachloro 1,1′3,3′-tetraethylbenzimid azolocarbocyanine iodide. Expression of mitochondrial and antioxidant genes was determined by real-time polymerase chain reaction. RPE cells show greater sensitivity to oxidative stress, reduction in expression of mitochondrial heat shock protein 70, uncoupling protein 2, and superoxide dismutase 3, and greater expression of superoxide dismutase 2 levels with increased chronological age. Changes in mitochondrial number, size, shape, matrix density, cristae architecture, and membrane integrity were more prominent in samples obtained from >60 years old compared to midage and younger donors. These mitochondria abnormalities correlated with lower ATP levels, reduced ΔΨm, decreased [Ca 2+ ] c , and increased sequestration of [Ca 2+ ] m in cells with advanced aging. Our study provides evidence for mitochondrial decay, bioenergetic deficiency, weakened antioxidant defenses, and increased sensitivity of RPE cells to oxidative stress with advanced aging. Our findings suggest that with increased severity of mitochondrial decay and oxidative stress, RPE function may be altered in some individuals in a way that makes the retina more susceptible to age-related injury.

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“…The outer BRB is formed by tight junctions between cells of the retinal pigment epithelium [19], which play an important role in trasporting nutrients from the blood to the outer retina. Chronic ocular inflammation can occur as a consequence of age progression [16], disease, injury and surgery [23,42,50]. Inflammation is typically associated with an increase in production of pro--inflammatory mediators [17], such as cytokines and chemokines, and persistent inflammation can lead to impaired vision and blindness [59].…”

Section: Introductionmentioning

confidence: 99%

Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation

Bianchi¹,

Ripandelli²,

Fehér³

et al. 2015

Folia Morphol

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Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration

Cited by 339 publications

References 64 publications

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis

Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress

Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation

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