Amyloid Precursor Protein Is Required for Normal Function of the Rod and Cone Pathways in the Mouse Retina

Ho, Tracy; Vessey, Kirstan A.; Cappai, Roberto; Dinet, Virginie; Mascarelli, Frédéric; Ciccotosto, Giuseppe D.; Fletcher, Erica L.

doi:10.1371/journal.pone.0029892

Cited by 34 publications

(38 citation statements)

References 61 publications

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“…Some examples of the terminology used in peer-reviewed literature from the last 10 years to describe the same head-turning movement using the same experimental set-up include optokinetic reflex (Barabas et al, 2011; Franco et al, 2009; Lu et al, 2010a; Zulliger et al, 2011), optokinetic response (Benkner et al, 2013; Della Santina et al, 2013; Ho et al, 2012; Joly et al, 2014; Lodha et al, 2010; Lu et al, 2010b; McGill et al, 2007; Prusky et al, 2006; Thompson et al, 2014; Tsai et al, 2014; Wang et al, 2010), optokinetic tracking (Della Santina et al, 2013; McGill et al, 2012a; McGill et al, 2012b; Volz et al, 2014; Wright et al, 2014; Wright et al, 2013), optokinetic nystagmus (Bricker-Anthony et al, 2014; Savigni et al, 2013; Selt et al, 2010), optomotor testing (Zhou et al, 2009), OMR (Abdeljalil et al, 2005; Kretschmer et al, 2013; Lund et al, 2006; Prusky et al, 2004; Puk et al, 2009; Rangarajan et al, 2011), optomotor reflex (Barabas et al, 2011; Barabas et al, 2013; Redfern et al, 2011), optomotor tracking (Burroughs et al, 2011; Douglas et al, 2005; Kaja et al, 2014), head-tracking reflex (Hoelter et al, 2008; Puk et al, 2008), reflexive head movements (Wang et al, 2010). Of the aforementioned terms, the optokinetic reflex/ optokinetic nystagmus should be used to describe eye-tracking, and the optokinetic response/ optokinetic tracking/ optomotor testing/ optomotor response/ optomotor reflex/ optomotor tracking/ head-tracking reflex/ reflexive head movements used to describe head-tracking.…”

Section: Behavioral Assays Measuring Deficits In Rodent Visual Promentioning

confidence: 99%

“…Implementations of this assay include either a motorized cylindrical drum which can be lined with various removable cards printed with alternating vertical black and white stripes arranged to produce a known frequency (Abdeljalil et al, 2005; Hoelter et al, 2008; Puk et al, 2008; Savigni et al, 2013; Thaung et al, 2002) or custom (Benkner et al, 2013; Kretschmer et al, 2013; Redfern et al, 2011; Thomas et al, 2010; Wang et al, 2010) and commercial computer-generated virtual cylinders, such as the popular OptoMotry system from Cerebral Mechanics (Barabas et al, 2013; Burroughs et al, 2011; Douglas et al, 2005; Franco et al, 2009; Ho et al, 2012; Joly et al, 2014; Lu et al, 2010a; Lu et al, 2010b; McGill et al, 2012a; McGill et al, 2007; McGill et al, 2012b; Prusky et al, 2004; Puk et al, 2009; Rangarajan et al, 2011; Thompson et al, 2014; Tsai et al, 2014; Volz et al, 2014; Wright et al, 2014; Wright et al, 2013; Zhou et al, 2009; Zulliger et al, 2011). The computer program displays rotating contrasting gratings at a constant speed in a virtual cylinder that also maintains a defined distance to the head of the animal (Burroughs et al, 2011; Douglas et al, 2005; Prusky et al, 2004).…”

Section: Behavioral Assays Measuring Deficits In Rodent Visual Promentioning

confidence: 99%

“…Many studies combine the use of behavioral measures such as testing of the optomotor reflex to obtain visual acuity and contrast sensitivity data with physiological readouts such as electroretinography or structural assays such as OCT to obtain a more comprehensive overall assessment of retinal and neuronal health of a given subject. These methods have been employed in combination to assess visual differences amongst mouse strains (Puk et al, 2008), visual deficits in zebrafish models (Allwardt et al, 2001; Bahadori et al, 2006; Biehlmaier et al, 2007; Bilotta et al, 2002; Brockerhoff, 2006; Brockerhoff et al, 1995; Kainz et al, 2003; Le et al, 2012; Stujenske et al, 2011; Van Epps et al, 2001), therapeutic effects of compounds in goldfish (Mora-Ferrer et al, 2005), normal retinal function (Ho et al, 2012), therapies in visually impaired mice (Boye et al, 2010) and rats (McGill et al, 2007). The correlation of these parameters with morphological changes in the retina (McGill et al, 2012a; McGill et al, 2012b), was used to assess changes during retinal degeneration (Barabas et al, 2013; Cammas et al, 2010; Pang et al, 2011; Samardzija et al, 2014; Wright et al, 2013) and dysfunction (Hoelter et al, 2008; Lodha et al, 2010), eye blast trauma (Bricker-Anthony et al, 2014), visual deficits in diabetes mouse (Aung et al, 2013; Aung et al, 2014) and rat models, after transgenic modification of RGCs (Tomita et al, 2010) or bipolar cells (Lagali et al, 2008) or after transplanting photoreceptors in the retina to improve vision (Schmucker and Schaeffel, 2006; Thompson et al, 2014).…”

Section: Future Developmentsmentioning

confidence: 99%

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Psychophysical testing in rodent models of glaucomatous optic neuropathy

Grillo

Koulen

2015

Experimental Eye Research

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Processing of visual information begins in the retina, with photoreceptors converting light stimuli into neural signals. Ultimately, signals are transmitted to the brain through signaling networks formed by interneurons, namely bipolar, horizontal and amacrine cells providing input to retinal ganglion cells (RGCs), which form the optic nerve with their axons. As part of the chronic nature of glaucomatous optic neuropathy, the increasing and irreversible damage and ultimately loss of neurons, RGCs in particular, occurs following progressive damage to the optic nerve head (ONH), eventually resulting in visual impairment and visual field loss. There are two behavioral assays that are typically used to assess visual deficits in glaucoma rodent models, the visual water task and the optokinetic drum. The visual water task can assess an animal’s ability to distinguish grating patterns that are associated with an escape from water. The optokinetic drum relies on the optomotor response, a reflex turning of the head and neck in the direction of the visual stimuli, which usually consists of rotating black and white gratings. This reflex is a physiological response critical for keeping the image stable on the retina. Driven initially by the neuronal input from direction-selective RGCs, this reflex is comprised of a number of critical sensory and motor elements. In the presence of repeatable and defined stimuli, this reflex is extremely well suited to analyze subtle changes in the circuitry and performance of retinal neurons. Increasing the cycles of these alternating gratings per degree, or gradually reducing the contrast of the visual stimuli, threshold levels can be determined at which the animal is no longer tracking the stimuli, and thereby visual function of the animal can be determined non-invasively. Integrating these assays into an array of outcome measures that determine multiple aspects of visual function is a central goal in vision research and can be realized, for example, by the combination of measuring optomotor reflex function with electroretinograms (ERGs) and optical coherence tomography (OCT) of the retina. These structure-function correlations in vivo are urgently needed to identify disease mechanisms as potential new targets for drug development. Such a combination of the experimental assessment of the optokinetic reflex (OKN) or optomotor reflex (OMR) with other measures of retinal structure and function is especially valuable for research on GON. The chronic progression of the disease is characterized by a gradual decrease in function accompanied by a concomitant increase in structural damage to the retina, therefore the assessment of subtle changes is key to determining the success of novel intervention strategies.

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Section: Behavioral Assays Measuring Deficits In Rodent Visual Promentioning

confidence: 99%

Section: Behavioral Assays Measuring Deficits In Rodent Visual Promentioning

confidence: 99%

Section: Future Developmentsmentioning

confidence: 99%

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Psychophysical testing in rodent models of glaucomatous optic neuropathy

Grillo

Koulen

2015

Experimental Eye Research

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“…33 APP was reported to accumulate in the optic nerve in rat 34 and mouse 35,36 glaucoma models. In the retina, APP immunostaining was observed in Müller glia, 37 RGCs, horizontal cells, cone bipolar cells, and amacrine cells, 38 suggesting that APP is present in both glial cells and neurons in the retina. In the present study, double immunostaining showed that APP is colocalized with vimentin-positive glial cells but not with neurofilaments in the normal optic nerve.…”

Section: Discussionmentioning

confidence: 99%

Axonal Protection via Modulation of the Amyloidogenic Pathway in Tumor Necrosis Factor–Induced Optic Neuropathy

Kojima

Kitaoka²,

Munemasa³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To examine the changes in and localization of phosphorylated presenilin1 (p-PS1) and amyloid precursor protein (APP) in the optic nerve after intravitreal injection of TNF and to investigate the role of c-secretase in the cleavage of APP in optic nerve degeneration.METHODS. Groups of rats were euthanatized at 1 or 2 weeks after intravitreal injection of TNF. Levels of p-PS1 protein in the optic nerve were determined by immunoblotting and immunohistochemistry. The localization of APP was determined by immunohistochemistry, and its downstream cleavage was determined by immunoprecipitation using 6E10 antibody followed by immunoblotting with an APP intracellular domain (AICD) antibody. The effect of a c-secretase inhibitor on TNFinduced optic nerve degeneration was determined by counting the number of axons.RESULTS. p-PS1 was increased in the optic nerve after TNF injection and was found to colocalize with vimentin and glial fibrillary acidic protein, markers of astrocytes. Immunoprecipitation using 6E10 antibody followed by immunoblotting with AICD antibody revealed an increase in c-secretase activation in the optic nerve after TNF injection, which was inhibited by treatment with the c-secretase inhibitor. Moreover, c-secretase inhibition significantly prevented the loss of axons in the optic nerve after TNF injection.CONCLUSIONS. The increase in p-PS1 and activation of c-secretase in the optic nerve may be associated with TNF-induced axonal degeneration. Modulation of c-secretase activity may be useful for the treatment of TNF-related optic neuropathy. (Invest Ophthalmol Vis Sci. 2012;53:7675-7683)

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“…Amyloid precursor protein (APP), a main player in the pathogenesis of Alzheimer’s disease, is expressed in inner retinal neurons and required for inner retinal function (Ho et al, 2012). Amyloid β (Aβ), the cleavage product of amyloid precursor protein (APP), has long been known to be the main constituent of senile plaques in brains of AD patients.…”

Section: Introductionmentioning

confidence: 99%

Iron increases APP translation and amyloid-beta production in the retina

Guo

Alekseev

et al. 2014

Experimental Eye Research

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Age-related macular degeneration (AMD) is the most common cause of blindness among older adults in developed countries, and retinal iron accumulation may exacerbate the disease. Iron can upregulate the production of amyloid precursor protein (APP). Since amyloid-β (Aβ), a byproduct of APP proteolysis, is found in drusen, the histopathological hallmark of AMD, we tested the role of iron in regulating APP and Aβ levels in the retinal pigment epithelial cell line ARPE-19. We found that treatment with ferric ammonium citrate (FAC) increases APP at the translational level. FAC treatment also results in increased generation of APP C-terminal fragments C83 and C99, the products of APP proteolysis by α- and β-secretase, respectively, as well as levels of Aβ42, a highly aggregative amyloid species. Additionally, retinal tissue sections from a patient with aceruloplasminemia, a disease causing iron overload in the retinal pigment epithelium (RPE), showed increased Aβ deposition in the RPE and drusen. Overall, our results suggest that RPE iron overload could contribute to Aβ accumulation in the retina.

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Amyloid Precursor Protein Is Required for Normal Function of the Rod and Cone Pathways in the Mouse Retina

Cited by 34 publications

References 61 publications

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Axonal Protection via Modulation of the Amyloidogenic Pathway in Tumor Necrosis Factor–Induced Optic Neuropathy

Iron increases APP translation and amyloid-beta production in the retina

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