SIRT1 Promotes RGC Survival and Delays Loss of Function Following Optic Nerve Crush

Zuo, Ling; Khan, Reas S.; Lee, Vivian; Dine, Kimberly; Wu, Wen-hsien; Shindler, Kenneth S.

doi:10.1167/iovs.13-12157

Cited by 71 publications

(80 citation statements)

References 30 publications

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“…Similar results have been seen in a rat model of ocular hypertension induced by saline injection into the episcleral vein(Prokai-Tatrai et al, 2013). In mice, ONC led to a significant decline in OKR after just 1 week and remained consistent for the 4 weeks of the study(Zuo et al, 2013). Neuroprotective strategies that yielded 100% protection of FG-labelled RGC at 2 weeks and 50% at 4 weeks had no significant effect on OKR, likely due to the axonal injury and lack of complete regeneration.…”

Section: Behavioral Testing- Optokinetic Reflexmentioning

confidence: 84%

Evaluating retinal ganglion cell loss and dysfunction

Mead

Tomarev

2016

Experimental Eye Research

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Retinal ganglion cells (RGC) bear the sole responsibility of propagating visual stimuli to the brain. Their axons, which make up the optic nerve, project from the retina to the brain through the lamina cribrosa and in rodents, decussate almost entirely at the optic chiasm before synapsing at the superior colliculus. For many traumatic and degenerative ocular conditions, the dysfunction and/or loss of RGC is the primary determinant of visual loss and are the measurable endpoints in current research into experimental therapies. To actually measure these endpoints in rodent models, techniques must ascertain both the quantity of surviving RGC and their functional capacity. Quantification techniques include phenotypic markers of RGC, retrogradely transported fluorophores and morphological measurements of retinal thickness whereas functional assessments include electroretinography (flash and pattern) and visual evoked potential. The importance of the accuracy and reliability of these techniques cannot be understated, nor can the relationship between RGC death and dysfunction. The existence of up to 30 types of RGC complicates the measuring process, particularly as these may respond differently to disease and treatment. Since the above techniques may selectively identify and ignore particular subpopulations, their appropriateness as measures of RGC survival and function may be further limited. This review discusses the above techniques in the context of their subtype specificity.

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Section: Behavioral Testing- Optokinetic Reflexmentioning

confidence: 84%

Evaluating retinal ganglion cell loss and dysfunction

Mead

Tomarev

2016

Experimental Eye Research

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“…Sirtuins have been reported to play important functions in various mouse models of retinal disease (Shindler et al 2007; Jaliffa et al 2009; Chen et al 2013; Zuo et al 2013; Zeng and Yang 2015). However, we found that individual deletion of Sirt1 , Sirt2 , Sirt4 , or Sirt6 did not cause retinal degeneration as assessed by fundus biomicroscopy nor did it cause retinal dysfunction by ERG.…”

Section: Discussionmentioning

confidence: 99%

Role of Sirtuins in Retinal Function Under Basal Conditions

Lin

Kubota

Mostoslavsky

et al. 2018

Retinal Degenerative Diseases

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Sirtuins are NAD+-dependent enzymes that govern cellular homeostasis by regulating the acylation status of their diverse target proteins. We recently demonstrated that both rod and cone photoreceptors rely on NAMPT-mediated NAD+ biosynthesis to meet their energetic requirements. Moreover, we found that this NAD+-dependent retinal homeostasis relies, in part, on maintenance of optimal activity of the mitochondrial sirtuins and of SIRT3 in particular. Nonetheless, it is unknown whether other sirtuin family members also play important roles in retinal homeostasis. Our results suggest that SIRT1, SIRT2, SIRT4, and SIRT6 are dispensable for retinal survival at baseline, as individual deletion of each of these sirtuins does not cause retinal degeneration by fundus biomicroscopy or retinal dysfunction by ERG. These findings have significant implications and inform future studies investigating the mechanisms underlying the central role of NAD+ biosyn-thesis in retinal survival and function.

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“…SIRT1 overexpression promoted RGC survival after optic nerve crush in mouse, an effect that was more pronounced than resveratrol treatment (Zuo et al, 2013). SIRT1 knockout did not increase RGC death over wildtype mice after optic nerve crush, suggesting complex interactions of cell death mechanisms.…”

Section: Addressing Energy Failure In Glaucomamentioning

confidence: 99%

“…SIRT1 knockout did not increase RGC death over wildtype mice after optic nerve crush, suggesting complex interactions of cell death mechanisms. Moreover, functional testing of the RGCs showed no difference among the SIRT1 activation, overexpression, or knockout groups, suggesting that axon degeneration occurred regardless of SIRT1 status (Zuo et al, 2013). The SIRT1 downregulation that resulted from 60 min of retina ischemia in mice could be reversed with once daily mangiferin treatment, a xanthonoid antioxidant (Kim et al, 2015).…”

Section: Addressing Energy Failure In Glaucomamentioning

confidence: 99%

Metabolic Vulnerability in the Neurodegenerative Disease Glaucoma

Inman

Harun‐Or‐Rashid

2017

Front. Neurosci.

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Axons can be several orders of magnitude longer than neural somas, presenting logistical difficulties in cargo trafficking and structural maintenance. Keeping the axon compartment well supplied with energy also presents a considerable challenge; even seemingly subtle modifications of metabolism can result in functional deficits and degeneration. Axons require a great deal of energy, up to 70% of all energy used by a neuron, just to maintain the resting membrane potential. Axonal energy, in the form of ATP, is generated primarily through oxidative phosphorylation in the mitochondria. In addition, glial cells contribute metabolic intermediates to axons at moments of high activity or according to need. Recent evidence suggests energy disruption is an early contributor to pathology in a wide variety of neurodegenerative disorders characterized by axonopathy. However, the degree to which the energy disruption is intrinsic to the axon vs. associated glia is not clear. This paper will review the role of energy availability and utilization in axon degeneration in glaucoma, a chronic axonopathy of the retinal projection.

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SIRT1 Promotes RGC Survival and Delays Loss of Function Following Optic Nerve Crush

Cited by 71 publications

References 30 publications

Evaluating retinal ganglion cell loss and dysfunction

Evaluating retinal ganglion cell loss and dysfunction

Role of Sirtuins in Retinal Function Under Basal Conditions

Metabolic Vulnerability in the Neurodegenerative Disease Glaucoma

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