Effect of hypoxia and glutamine or glucose deprivation on the expression of retinoblastoma and retinoblastoma-related genes in ERN1 knockdown glioma U87 cell line

The expression of retinoblastoma and several retinoblastoma-related genes was studied in glioma cell line U87 and its subline with knockdown of ERN1 (endoplasmic reticulum—nuclei-1), the main endoplasmic reticulum stress sensing and signaling enzyme. It was shown that a blockade of the ERN1 enzyme function increases the expression levels of retinoblastoma, retinoblastoma-like 1 and most retinoblastoma related genes: EID1, JARID1B, E2F1, E2F3, RBAP48 and CTIP, does not change RNF40 and RBAP46 and decreases KDM5A. We have also demonstrated that hypoxia reduces the expression levels of retinoblastoma, EID1, and E2F1 in ERN1-deficient glioma cells only. At the same time, the expression levels of retinoblastoma-like 1, E2F3, RBAP46, RBAP48 and CTIP decrease, while JARID1B and RBBP2 increase in both types of cells in hypoxic conditions, but the expression is much stronger in cells with suppressed function of ERN1. The expression level of JARID1B and KDM-5A mRNA is also enhanced in glutamine deprivation condition in both tested cell types, moreover, this effect is amplified by the blockade of the ERN1 enzyme function. The expression levels of retinoblastoma, EID1, RBAP48, and E2F3 are decreased in glutamine deprivation condition only in ERN1-deficient glioma cells, but RBL1, CTIP, RBAP46, and E2F1—in both tested cell types with more significant effect in ERN1-deficient cells. Glucose deprivation condition leads to a decrease of expression levels of retinoblastoma, RBL1, E2F3, RBAP46, and RBAP48 in both used cell types and of EID1 and E2F1 only in glioma cells with suppressed function of signaling enzyme ERN1. Thus, expression levels of retinoblastoma and most retinoblastoma-related genes are increased under a blockade of ERN1 enzyme function and significantly changed in hypoxia, glucose or glutamine deprivation conditions both in control U87 cells and ERN1-deficient cells, but inhibition of the unfolded protein response sensor ERN1 predominantly enhances these effects. Moreover, it is possible that the induction of the expression of retinoblastoma and most retinoblastoma-related genes after knockdown of ERN1 plays an important role in suppression of glioma proliferation.

黄斑微孔:发病机制和自然病史

Aims: To study the natural history and evaluate optical coherence tomography (OCT) and the retinal thickness analyser (RTA) in patients with macular microholes. Methods: The medical records of 22 patients with a well demarcated red intraretinal foveal or juxtafoveal defect were reviewed. Fluorescein angiography (FA), RTA, and OCT were performed. The main outcome measures were visual acuity (VA), and OCT and RTA characteristics of microholes. Long term follow up was available in 13 eyes of 12 patients. Results: The patients had a mean age of 50 years and a mean refractive error of-0.93 dioptres. The presenting symptom was a central scotoma in 14 eyes and metamorphopsia in eight eyes. All patients had a corrected VA ranging from 20/16 to 20/125, with 20 out of 24 eyes (83% ) having a VA ≥ 20/40. Symptoms remained stable or improved in 16 out of 22 patients (72% ). OCT 2 findings were normal but an abnormality of the outer retina and/or a defect of the retinal pigment epithelium (RPE) were demonstrated on OCT3 in 15 of 18 eyes (83% ). The RTA topographic map demonstrated a defect at the site of the microhole in two out of 12 eyes. Conclusion: Although biomicroscopic examination suggested an inner foveal defect, the OCT3 scans demonstrated a localised abnormality of the outer retina and/or RPE which could not be resolved using OCT 2. Macular microholes have a favourable long term prognosis with stable VA. Bilateral involvement is uncommon.

中央静脉阻塞行玻璃体切割术和放射状视神经切开术的视力和黄斑解剖结构变化

Background: Central retinal vein occlusion (CRVO) is a common retinal vascular disorder and a leading cause of visual loss. It is thought to arise from vascul ar obstruction at the level of the lamina cribrosa. The purpose of the study rep orted here was to evaluate the potential benefit of radial optic neurotomy (RON) and determine its effect on foveal thickness and macular volume in patients wit h CRVO. Methods: We conducted a prospective pilot study of ten patients with CRV O. Visual acuity (VA) score measured with the Early Treatment Diabetic Retinopat hy Study chart and the corresponding Snellen equivalent were assessed before and 6 months after surgery. Colour fundus photography, fluorescein angiography (FA) and optical coherence tomography (OCT) were carried out before and at 2, 6, 12 and 24 weeks after surgery. Foveal thickness and macular volumes were assessed u sing OCT. Results: Visible reperfusion was observed in four of the ten patients at the time of surgery. VA score improved in eight of the ten patients from a me dian score of 11.50 (range 0-68) to a median score of 35.00 (range 3-79). Macu lar volumes decreased in six of seven patients from a median of 4.99mm3(range 2. 68-6.77) to amedian of 3.11mm3 (range 1.11-5.02). Foveal thickness decreased i n six of seven patients from a median of 596.50 μm (range 338.50-745.50) to a median of 330.50 μm (range 118-634.50). Six of ten patients developed a chorio retinal venous anastomosis. Macular oedema on OCT persisted in six of ten patien ts. Conclusions: We observed an improvement in VA score and a corresponding redu ction in foveal thickness and macular volume following RON, but macular oedema p ersisted in 60%of patients. Whilst op timisation of patient selection criteria remains a challenge, this pilot study suggests that RON has a beneficial effect on VA in patients presenting with CRV O.