Impact of aging and diet restriction on retinal function during and after acute intraocular pressure injury

Kong, Yu; Bergen, Nicole Van; Bui, Bang V.; Chrysostomou, Vicki; Trounce, Ian A.; Crowston, Jonathan G

doi:10.1016/j.neurobiolaging.2011.11.026

Cited by 75 publications

(58 citation statements)

References 67 publications

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“…It had been reported that in 3-month-old C57BL/6 mice with IOP elevation of 50 mm Hg for 30 minutes, near-complete recovery of ERG responses from RGCs, bipolar cells, and photoreceptors was found 7 days following challenge. 16 Although the duration may be different, the level of IOP is similar in our study (50.5 6 3.6 mm Hg, Fig. 2B).…”

Section: Discussionsupporting

confidence: 74%

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A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture

Liu

Flanagan

2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To develop a chronic ocular hypertension mouse model by inducing intraocular pressure (IOP) elevation using a suture technique previously developed for rats.METHODS. C57BL/6 mice were given monocular circumlimbal suture (10/0) placement under anesthesia (ketamine/xylazine). The suture was left in place for 12 weeks (n ¼ 10). A control group had the same treatment while it was removed after day 1 (n ¼ 10). Intraocular pressure, electroretinogram (ERG), and optical coherence tomography (OCT) were measured in both groups for 12 weeks. At week 12, animals were euthanized and retina was harvested for histologic assessment.RESULTS. In the group with extended suture placement, IOP spiked from 14.3 6 0.9 to 48.4 6 4.8 mm Hg immediately after suture implantation. At day 1, it declined to 33.2 6 3.7 mm Hg and remained elevated for 12 weeks. In the suture removal group, IOP normalized to baseline within a day following suture removal. In the group with prolonged IOP elevation, the retinal ganglion cell (RGC) mediated ERG responses continued to exacerbate and were significantly reduced by week 12 (P < 0.001). Progressive loss of retinal nerve fiber layer was found and it became significant from week 4 (P < 0.001). At week 12, significant loss of RGCs (P < 0.001) was noted. In the IOP normalization group, no alteration in ERG, OCT, and RGC counting was observed.CONCLUSIONS. The circumlimbal suture approach produces a mild chronic IOP elevation in mice. Functional and structural changes under model induction are largely independent of the initial IOP spike.Keywords: glaucoma, intraocular pressure, electroretinogram, optical coherence tomography, ganglion cell G laucoma is a chronic ocular disease, which is characterized by selective retinal ganglion cell (RGC) degeneration and progressive visual field loss. Elevated intraocular pressure (IOP) is a critical risk factor for disease development, and IOP lowering is the mainstay of disease management. [1][2][3] Over the past few decades, a variety of rodent models have been developed to simulate human glaucoma. [4][5][6][7] These models aim to induce either acute or chronic ocular hypertension leading to glaucomatous-like changes. By using such models, investigators have made significant insights into understanding the pathogenesis of the disease.Previously, a rat model of chronic IOP elevation using conjunctival circumlimbal suture was developed. 8,9 This minimally invasive technique employed the concept of oculopression to produce elevated IOP. [10][11][12] An advantage of the suture compression model is that it is not associated with ocular tissue penetration or traumatization, and therefore relatively preserves the immune privilege of the eye. It was reported that a mild, chronic IOP elevation was induced for at least 15 weeks following an initial IOP spike that appeared immediately after suture placement. Progressive loss of RGC function, retinal nerve fiber layer (RNFL) defect, and eventual cell death in the ganglion cell layer were observed under model induction, ...

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Section: Discussionsupporting

confidence: 74%

“…Moreover, this study also showed that no significant reduction in retinal blood flow at IOP levels lower than 70 mm Hg was found. 16 The same findings are reported in rats. 15,33 Therefore, it is reasonable to assume that there will be no significant retinal ischemia following suture placement in our model.…”

Section: Discussionsupporting

confidence: 68%

A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture

Liu

Flanagan

2017

Invest. Ophthalmol. Vis. Sci.

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“…The slow progressive loss of RGC that is characteristic of glaucoma and unlike ONC/ONT makes it unsurprising that dysfunction precedes RGC loss. The dysfunction (as measured by pSTR) is transient and its reversal coincides with a normalisation of IOP (Kong et al, 2012). Comparing RGC numbers to function can be difficult as certain RGC phenotypic markers are more intimately linked to dysfunction than others.…”

Section: Functional Assessmentsmentioning

confidence: 99%

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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“…Others have combined experimental glaucoma with electroretinography (ERG) as a non-invasive test to measure the impact of short term IOP exposures on the ONH and retina, and have used this system to determine the effects of age, dietary restriction and mitochondrial abnormalities on their response (Kong et al, 2011, 2012). However, the exact contribution of ischemia to this response is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effect of elevated intraocular pressure and reduced ocular perfusion pressure on retinal capillary bed filling and total retinal blood flow in rats by OMAG/OCT

Zhi

Cepurna

Johnson

et al. 2015

Microvascular Research

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Purpose To determine if retinal capillary filling is preserved in the face of acutely elevated intraocular pressure (IOP) in anesthetized rats, despite a reduction in total retinal blood flow (RBF), using optical microangiography/optical coherence tomography (OMAG/OCT). Methods OMAG provided the capability of depth-resolved imaging of the retinal microvasculature down to the capillary level. Doppler OCT was applied to measure the total RBF using an enface integration approach. The microvascular pattern, capillary density, and total RBF were monitored in vivo as the IOP was increased from 10 to 100 mm Hg in 10 mm Hg intervals and returned back to 10 mm Hg. Results In animals with mean arterial pressure (MAP) of 102 ± 4 mm Hg (n = 10), when IOP was increased from 0 to 100 mm Hg, the capillary density remained at or above 80% of baseline for the IOP up to 60 mm Hg [or ocular perfusion pressure (OPP) at 40 mm Hg]. This was then decreased, achieving 60% of baseline at IOP 70 mm Hg and OPP of 30 mm Hg. Total RBF was unaffected by moderate increases in IOP up to 30 mm Hg, beyond which total RBF decreased linearly, reaching 50% of baseline at IOP 60 mm Hg and OPP 40 mm Hg. Both capillary density and total RBF were totally extinguished at 100 mm Hg, but fully recovered when IOP returned to baseline. By comparison, a separate group of animals with lower MAP (mean = 75 ± 6 mm Hg, n = 7) demonstrated comparable decreases in both capillary filling and total RBF at IOPs that were 20 mm Hg lower than in the initial group. Both were totally extinguished at 80 mm Hg, but fully recovered when IOP returned to baseline. Relationships of both parameters to OPP were unchanged. Conclusion Retinal capillary filling and total RBF responses to IOP elevation can be monitored non-invasively by OMAG/OCT and both are influenced by OPP. Retinal capillary filling was relatively preserved down to a perfusion pressure of 40 mm Hg, despite a linear reduction in total RBF.

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Impact of aging and diet restriction on retinal function during and after acute intraocular pressure injury

Cited by 75 publications

References 67 publications

A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture

A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture

Evaluating retinal ganglion cell loss and dysfunction

Evaluation of the effect of elevated intraocular pressure and reduced ocular perfusion pressure on retinal capillary bed filling and total retinal blood flow in rats by OMAG/OCT

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