Functional and Morphologic Comparison of Two Methods to Produce Transient Retinal Ischemia in the Rat

Rosenbaum, Daniel M.; Rosenbaum, Pearl S.; Singh, Manjeet; Gupta, Gaurav; Gupta, Himanshu; Li, Bing; Roth, Steven

doi:10.1097/00041327-200103000-00015

Cited by 54 publications

(48 citation statements)

References 27 publications

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“…It appears that a "maturation" phenomenon occurs whereby histologic damage becomes more evident with increasing times after ischemia and that the functional (ERG) disturbance predates morphologic changes. 27 Our results further support that functional measurements revealed injury at a time when retinal morphologic features appear relatively normal because no evident changes in retinal morphologic features were observed in eyes from diabetic animals even 10 weeks after the diabetes onset. Although it is becoming increasingly clear that retinal cells are also affected by diabetes, the degeneration rate of the inner retina appears to vary in different animal models, with a clear progression over the time of diabetes.…”

Section: Discussionsupporting

confidence: 88%

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Fernandez

Sande

Chianelli

et al. 2011

The American Journal of Pathology

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Diabetic retinopathy is a leading cause of acquired blindness. Available treatments are not very effective. We investigated the effect of a weekly application of retinal ischemia pulses (ischemic conditioning) on retinal damage induced by experimental diabetes. Diabetes was induced by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 minutes; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, whereas the contralateral eye was submitted to a sham procedure. Diabetic retinopathy was evaluated in terms of i) retinal function (electroretinogram and oscillatory potentials), ii) integrity of blood-retinal barrier (by albumin-Evans blue complex leakage and astrocyte glial fibrillary acidic protein IHC), iii) optical and electron microscopy histopathologic studies, and iv) vascular endothelial growth factor levels (using Western blot analysis and IHC). Brief ischemia pulses significantly preserved electroretinogram a-and b-wave and oscillatory potentials, avoided albumin-Evans blue leakage, prevented the decrease in astrocyte glial fibrillary acidic protein levels, reduced the appearance of retinal edemas, and prevented the increase in vascular endothelial growth factor levels induced by experimental diabetes. When the application of ischemia pulses started 6 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies for diabetic retinopathy treatment.

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Section: Discussionsupporting

confidence: 88%

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Fernandez

Sande

Chianelli

et al. 2011

The American Journal of Pathology

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“…Inhibitors of XO have been successfully used to reduce ischemiainduced changes in model systems [32]. In our study, we detected significantly lower levels of XO activity in the PGA treatment groups.…”

Section: Discussionsupporting

confidence: 55%

“…A growing body of evidence indicates that the tissue injury observed after reperfusion is due to the reintroduction of oxygen rather than a delayed manifestation of injury caused by ischemia [31,35]. Up to now, various experimental designs have been described for the induction of ischemia-reperfusion damage in the retina, as vessel occlusion by clamping [1,8,9,13,24,28,30,32,33]. In the present study, we used the method of raising intraocular pressure above the arterial opening pressure.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Protective Effects of Prostaglandin Analogues in the Ischemia and Reperfusion Model of Rabbit Eyes

et al. 2009

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This study was planned to investigate the neuroprotective potentials of three commercially available prostaglandin analogues (PGA), in the ischemia and reperfusion model (I/R). Thirty New Zealand rabbits were divided into 5 groups and except for the control group (non-ischemic, non-treated), 0.9% NaCl, bimatoprost, latanoprost, or travoprost were applied to both eyes of animals of the respective groups for 1 week. At the end of treatment, ischemia was induced in both eyes of the 4 treatment groups by anterior chamber irrigation of the animals for 60 min. Following 24 h reperfusion, the animals were sacrified. Enucleated eyes and retinal tissues were investigated by light microscopy, electron microscopy, immunohistochemicstry for retinal histopathology, intracellular and apoptotic cells and by retinal morphometry. Vitreous samples were biochemically investigated for probable role of reactive oxygen species, by measuring xanthine oxidase (XO) activity. Analysis of morphometric measurements and vitreous XO activity revealed significant differences between the PGAtreated groups and the NaCl-treated group (P<0.05). Similarly, apoptotic cell counts in different retinal layers showed that PGA-treated groups had fewer apoptotic cells in all retinal layers than the NaCl-treated ischemic group (P<0.05). PGA may have high protective potential for different retinal layers and cells. Biochemical analysis of vitreous showed that all PGAs decreased vitreous XO activity significantly compared to the NaCl-treated group (P<0.05). However we could not find any statistically significant differences among the analogues. PGAs may reduce the injury induced by I/R, through the inhibition of XO activity, and it seems that their effects are elicited through numerous pathways.

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“…Various experimental designs have been set up for the induction of ischemiareperfusion damage in the retina, that is, 2-vessel occlusion by bilateral clamping of the common carotid arteries [31], 4-vessel occlusion by clamping of the vertebral arteries as well as the common carotid arteries [31], central retinal artery occlusion by ligation of the optic nerve [46,47], raised intraocular pressure above the arterial opening pressure [45,46], microembolization [46,47], and laser coagulation of peripheral retinal arteries [31,48,49]. In the present study, we used the method of optic nerve ligation [21], including the central artery and vein.…”

Section: Block and Schwarz [31] Demonstrated Reversible Erg Changes Wmentioning

confidence: 99%

Expression of antioxidant enzymes in rat retinal ischemia followed by reperfusion

Agardh¹,

Gustavsson²,

Hagert³

et al. 2006

Metabolism

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To evaluate the expression and protein levels of antioxidant enzymes in the rat retina exposed to oxidative stress induced by ischemia-reperfusion injury. Retinal ischemia was induced in female Wistar rats by ligation of the optic nerve and vessels behind the left eye bulb, and was followed by reperfusion for 0, 3, 6, or 24 hours. The right eye served as control. RNA and protein were extracted simultaneously from each retina. Expressions of the endogenous antioxidant enzymes glutathione peroxidase (GPx1), catalase (CAT), copper/zinc superoxide dismutase, manganese superoxide dismutase, and the catalytic subunit of glutamylcysteine ligase (GCLc) were analyzed with real-time reverse transcription polymerase chain reaction and related to the endogenous control cyclophilin B. Protein levels were measured with Western blot analysis. During the early phase (0 or 3 hours) of reperfusion, no changes were seen in enzyme expression. After 6 hours, GCLc expression increased by a factor of 1.14 (P = 0.034), followed by a decline of 0.80 after 24 hours (P = 0.00004), according to the comparative Ct method. After 24 hours of reperfusion, GPx1 expression increased by a factor of 1.14 (P = 0.028), and CAT had decreased by 0.82 (P = 0.022). Expressions of copper/zinc superoxide dismutase and manganese superoxide dismutase showed a tendency toward a decrease by factors of 0.86 (P = 0.055) and 0.88 (P = 0.053), respectively, after 24 hours.Protein levels did not differ for any of the antioxidants, regardless of reperfusion time. The slightly increased messenger RNA expression of GPx1 after 24 hours of reperfusion with a concomitant very modest decrease in CAT and GCLc expression and no change in protein levels indicate a very modest, if any, response to oxidative stress generated by ischemia followed by reperfusion in rat retina.

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Functional and Morphologic Comparison of Two Methods to Produce Transient Retinal Ischemia in the Rat

Cited by 54 publications

References 27 publications

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Comparison of the Protective Effects of Prostaglandin Analogues in the Ischemia and Reperfusion Model of Rabbit Eyes

Expression of antioxidant enzymes in rat retinal ischemia followed by reperfusion

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