Complementation Test of<i>Rpe65</i>Knockout and Tvrm148

Wright, Charles B.; Chrenek, Micah A; Foster, Stephanie L.; Duncan, Todd; Redmond, T. Michael; Pardue, Machelle T.; Boatright, Jeffrey H; Nickerson, John M.

doi:10.1167/iovs.13-12336

Cited by 8 publications

(20 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…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). The combination of these assessments has the enormous potential to increase our knowledge of the normal function of the retina and visual system and of disease mechanisms to both enable and hasten the development of much needed novel effective therapies.…”

Section: Future Developmentsmentioning

confidence: 99%

See 2 more Smart Citations

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Grillo

Koulen

2015

Experimental Eye Research

View full text Add to dashboard Cite

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.

show abstract

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%

See 1 more Smart Citation

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Grillo

Koulen

2015

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…Several missense mutations have been shown to cause rapid degradation of RPE65 in the kidney-derived HEK cell line (16–19) and mouse models (20–22). The molecular basis for the rapid degradation of mutant RPE65 is unknown.…”

Section: Introductionmentioning

confidence: 99%

“…The loss of RPE65 function involves at least two distinct mechanisms: loss of catalytic activity ( 3 , 5 ) and a lower expression level of RPE65. Several missense mutations have been shown to cause rapid degradation of RPE65 in the kidney-derived HEK cell line ( 16 – 19 ) and mouse models ( 20 – 22 ). The molecular basis for the rapid degradation of mutant RPE65 is unknown.…”

Section: Introductionmentioning

confidence: 99%

Rescue of Enzymatic Function for Disease-associated RPE65 Proteins Containing Various Missense Mutations in Non-active Sites

Izumi

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Disease-causing mutations reduce RPE65 protein levels with unknown mechanisms.Results: Interaction of 26 S proteasome non-ATPase regulatory subunit 13 with mutant RPE65s mediates degradation of misfolded RPE65s via the ubiquitin-proteasome pathway.Conclusion: Many mutant RPE65s with non-active site mutations are catalytically active and can be rescued.Significance: Low temperature and chaperones that rescue enzymatic function of mutant RPE65s are therapeutic candidates.

show abstract

Inverse correlation between fatty acid transport protein 4 and vision in Leber congenital amaurosis associated with RPE65 mutation

Gordon

Bazán

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Fatty acid transport protein 4 (FATP4), a transmembrane protein in the endoplasmic reticulum (ER), is a recently identified negative regulator of the ER-associated retinal pigment epithelium (RPE)65 isomerase necessary for recycling 11-cis-retinal, the light-sensitive chromophore of both rod and cone opsin visual pigments. The role of FATP4 in the disease progression of retinal dystrophies associated with RPE65 mutations is completely unknown. Here we show that FATP4-deficiency in the RPE results in 2.8-fold and 1.7-fold increase of 11-cis- and 9-cis-retinals, respectively, improving dark-adaptation rates as well as survival and function of rods in the Rpe65 R91W knockin (KI) mouse model of Leber congenital amaurosis (LCA). Degradation of S-opsin in the proteasomes, but not in the lysosomes, was remarkably reduced in the KI mouse retinas lacking FATP4. FATP4-deficiency also significantly rescued S-opsin trafficking and M-opsin solubility in the KI retinas. The number of S-cones in the inferior retinas of 4- or 6-mo-old KI;Fatp4−/− mice was 7.6- or 13.5-fold greater than those in age-matched KI mice. Degeneration rates of S- and M-cones are negatively correlated with expression levels of FATP4 in the RPE of the KI, KI;Fatp4+/−, and KI;Fatp4−/− mice. Moreover, the visual function of S- and M-cones is markedly preserved in the KI;Fatp4−/− mice, displaying an inverse correlation with the FATP4 expression levels in the RPE of the three mutant lines. These findings establish FATP4 as a promising therapeutic target to improve the visual cycle, as well as survival and function of cones and rods in patients with RPE65 mutations.

show abstract

Complementation Test ofRpe65Knockout and Tvrm148

Cited by 8 publications

References 66 publications

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Rescue of Enzymatic Function for Disease-associated RPE65 Proteins Containing Various Missense Mutations in Non-active Sites

Inverse correlation between fatty acid transport protein 4 and vision in Leber congenital amaurosis associated with RPE65 mutation

Contact Info

Product

Resources

About