Preventing Retinal Detachment–Associated Photoreceptor Cell Loss in Bax-Deficient Mice

Liu, Yang; Bula, Deisy V.; Arroyo, Jorge G.; Chen, Dong F.

doi:10.1167/iovs.03-0827

Cited by 87 publications

(86 citation statements)

References 32 publications

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“…The results also revealed that exogenous EPO significantly upregulated the expression of Bcl-X L and reduced the expression of caspase-3, indicating that the combination of EPO and EPOR may induce Bcl-2 antiapoptotic gene expression by signal transduction pathways, and inhibits apoptosis by suppressing the mitochondrial release of cytochrome C and regulating intracellular Ca 2 þ levels. Histopathological findings revealed that the ONL thickness in all groups was only slightly reduced at 14 d after RD; although this reduction was significant, it was less than that reported in previous studies, such as those of Berglin et al 33 and Yang et al, 34 who reported that the ONL thickness was reduced by half at 14 days after local RD in rabbits. This variation may be due to inter-species differences, the concentrations of sodium hyaluronate used, or the retinal uplift height.…”

Section: Eyecontrasting

confidence: 60%

Safety and efficacy of intravitreal injection of recombinant erythropoietin for protection of photoreceptor cells in a rat model of retinal detachment

Xie

Chen

et al. 2011

Eye

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Purpose To elucidate the safety and efficacy of exogenous erythropoietin (EPO) for the protection of photoreceptor cells in a rat model of retinal detachment (RD). Methods Recombinant rat EPO (400 ng) was injected into the vitreous cavity of normal rats to observe the eye manifestations. Retinal function was assessed by flash electroretinograms. Histopathological examination of retinal tissue was performed at 14 days and 2 months after injection, respectively. To investigate the inhibitory effect of EPO on photoreceptor cell apoptosis in RD rats, 100, 200, or 400 ng EPO was injected into the vitreous cavity immediately after RD model establishment. Apoptosis of photoreceptor cells was determined at 3 days after injection. Caspase-3 activation was measured by western blot analysis and immunofluorescence, respectively, and the level of Bcl-X L expression was analyzed by western blot. Results Intravitreal injection of EPO 400 ng into normal rats had no significant impact on retinal function, morphology, or structure. Apoptosis of retinal photoreceptor cells apparently increased after RD and was significantly reduced following EPO treatment. The thickness of the outer nuclear layer in the RD þ 400 ng group was significantly thicker than that in other experimental RD groups both at 14 days and at 2 months after RD (Po0.05). Western blot and immunofluorescence analyses showed decreased caspase-3 activation and increased Bcl-X L expression following EPO treatment. Conclusion Intravitreal injection of EPO 400 ng is safe, and EPO may suppress caspase-3 activation and enhance Bcl-X L expression, resulting in inhibition of apoptosis and protection of photoreceptor cells.

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Section: Eyecontrasting

confidence: 60%

Safety and efficacy of intravitreal injection of recombinant erythropoietin for protection of photoreceptor cells in a rat model of retinal detachment

Xie

Chen

et al. 2011

Eye

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“…Earlier studies mainly focused on the mitochondrion-mediated pathway; the existence of mitochondrion-mediated pathway has been confirmed in the apoptosis of photoreceptors whereby the inhibition of key factors in above pathway prevented the photoreceptors from apoptosis. [8][9][10] However, the inhibitors can only partly rescue photoreceptors, suggesting the existence of other pathways for the apoptosis process after RD.…”

Section: Introductionmentioning

confidence: 99%

Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication

Liu

Qian

Wang

et al. 2009

Eye

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Purpose To investigate the expression of endoplasmic reticulum (ER) stress-related genes, glucose-regulated protein 78 (GRP78) and growth arrest DNA damage-inducible gene 153 (GADD153)/CPEBP homologous protein (CHOP), in rat retinal detachment (RD) model. Materials and methods At various time points after RD, the apoptosis of retinal cells was detected by TdT-mediated fluorescein-16-dUTP nick-end labelling (TUNEL) assay; GRP78 and GADD153 mRNA levels were detected by reverse transcription (RT)-PCR; proteins were detected by western blotting analysis; protein distributions in the retinal cells were observed by immunofluorescence using laser-scanning confocal microscope. Results After RD, the apoptosis was peaked on 2-4 d and then dropped down. The GRP78 mRNA and GADD153 mRNA levels in RD groups on 0.5, 1, 2, and 4 d were all significantly higher than those in the control group (Po0.05). The expression of GRP78 mRNA peaked on 1-2 d after RD. Expression of GRP78 protein was significantly higher than that in the normal control group on 0.5, 1, 2, 4, 8, 16, and 32 d after RD (Po0.05). The expression of GRP78 protein was observed in all the layers of retina in the RD groups, and peaked on 8, 16, and 32 d. The expression of GADD153 protein, mostly in photoreceptor layers, was significantly higher than that in the control group on 0.5, 1, 2, and 4 d after RD (Po0.05). Conclusions ER stress-related markers, GRP78 and GADD153, are elevated after RD.The elevation of GADD153 is in parallel with the post-RD apoptosis of retinal cells, suggesting that ER stress-mediated death is likely to be activated after RD and involved in post-RD vision loss.

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“…7 Other events affecting the photoreceptors include apoptosis and loss of structural integrity, both of which are thought to contribute to the vision impairment following RD. [8][9][10] Misalignment of photoreceptors, measured by Stiles-Crawford function, may also be a problem after RD repair. 11,12 Mü ller cells have been shown to react within 15 min of RD, 13 with proliferation and hypertrophy of their processes seen as little as two days postdetachment.…”

Section: Introductionmentioning

confidence: 99%

“…10,24,25 Accumulation of glutamate has been observed in animal models of retinal ischaemia, [26][27][28][29] and animal studies of RD have shown excess glutamate levels and lower glutamine synthetase (GS) activity within the retina. [30][31][32] Moreover, increased levels of glutamate were recently found in the vitreous fluid of human subjects with RD.…”

Section: Introductionmentioning

confidence: 99%

Amino-acid levels in subretinal and vitreous fluid of patients with retinal detachment

Bertram

Bula

Pulido

et al. 2007

Eye

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Purpose To compare the concentration of amino acids in subretinal and vitreous fluid of patients with primary rhegmatogenous retinal detachment to that of control vitreous. Methods This prospective, observational study measured amino-acid levels in subretinal fluid of patients undergoing scleral buckle placement (n ¼ 20) and vitreous fluid in patients undergoing pars plana vitrectomy (n ¼ 5) for primary retinal detachment. Vitreous fluid from patients undergoing vitrectomy for macular hole (n ¼ 7) or epiretinal membrane (n ¼ 3) served as a control. Subretinal fluid and control vitreous were analysed using high-pressure liquid chromatography. Retinal detachment vitreous was analysed using capillary electrophoresis-laser-induced fluorescence. Results Mean levels of glutamate (27.071.7 lM), aspartate (4.174.0 lM), and glycine (44.1731.0 lM) in subretinal fluid and glutamate (13.4711.9 lM) in the vitreous were significantly elevated in retinal detachment compared to control vitreous. A significant, positive association was observed between levels of aspartate and glutamate in subretinal fluid (Spearman's correlation coefficient: 0.74, Po0.01). Mean arginine levels did not differ significantly between subretinal fluid and control vitreous. Levels of alanine, tyrosine, valine, isoleucine, leucine, and phenylalanine were significantly lower in subretinal fluid compared to control vitreous (all Po0.01). Conclusions Glutamate levels in subretinal fluid and vitreous of patients with primary retinal detachment is significantly elevated in comparison to control vitreous. This finding lends further support to the hypothesis that elevated glutamate levels may result from ischaemia of the outer retina secondary to retinal detachment.

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Preventing Retinal Detachment–Associated Photoreceptor Cell Loss in Bax-Deficient Mice

Cited by 87 publications

References 32 publications

Safety and efficacy of intravitreal injection of recombinant erythropoietin for protection of photoreceptor cells in a rat model of retinal detachment

Safety and efficacy of intravitreal injection of recombinant erythropoietin for protection of photoreceptor cells in a rat model of retinal detachment

Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication

Amino-acid levels in subretinal and vitreous fluid of patients with retinal detachment

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