[Retracted] Downregulation of CKS1B restrains the proliferation, migration, invasion and angiogenesis of retinoblastoma cells through the MEK/ERK signaling pathway.

Following the publication of the above paper, it has been drawn to the Editors' attention by a concerned reader that certain of the lumen formation assay data shown in Fig. 5A on p. 112 were strikingly similar to data appearing in different form in another article written by different authors at different research institute, which had already been published in the journal Biomedicine & Pharmacotherapy prior to the submission of this paper to International Journal of Molecular Medicine, and which has also subsequently been retracted. In view of the fact that the contentious data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 103­114, 2019; DOI: 10.3892/ijmm.2019.4183].

Molecular mechanism of high glucose-induced mitochondrial DNA damage in retinal ganglion cells.

Mitochondrial DNA damage in retinal ganglion cells (RGCs) may be closely related to lesions of glaucoma. RGCs were cultured with different concentrations of glucose and grouped into 3 groups, namely normal control (NC) group, Low-Glu group, and High-Glu group. Cell viability was measured with cell counting kit-8, and cell apoptosis was measured using flow cytometry. The DNA damage was measured with comet assay, and the morphological changes of damaged mitochondria in RGCs were observed using TEM. Western blot analyzed the expression of MRE11, RAD50, and NBS1 protein. Cell viability of RGCs in Low-Glu and High-Glu groups were lower than that of NC group in 48 and 96 h. The cell apoptosis in NC group was 4.9%, the Low-Glu group was 12.2% and High-Glu group was 24.4%. The comet imaging showed that NC cells did not have tailings, but the low-Glu and high-Glu group cells had tailings, indicating that the DNA of RGCs had been damaged. TEM, mitochondrial membrane potential, ROS, mitochondrial oxygen consumption, and ATP content detection results showed that RGCs cultured with high glucose occurred mitochondrial morphology changes and dysfunction. MRE11, RAD50, and NBS1 protein expression associated with DNA damage repair pathway in High-Glu group declined compared with Low-Glu group. Mitochondrial DNA damage caused by high glucose will result in apoptosis of retinal ganglion cells in glaucoma.

The accuracy of intraocular lens power calculation formulas based on artificial intelligence in highly myopic eyes: a systematic review and network meta-analysis.

Objective: To systematically compare and rank the accuracy of AI-based intraocular lens (IOL) power calculation formulas and traditional IOL formulas in highly myopic eyes. Methods: We screened PubMed, Web of Science, Embase, and Cochrane Library databases for studies published from inception to April 2023. The following outcome data were collected: mean absolute error (MAE), percentage of eyes with a refractive prediction error (PE) within ±0.25, ±0.50, and ±1.00 diopters (D), and median absolute error (MedAE). The network meta-analysis was conducted by R 4.3.0 and STATA 17.0. Results: Twelve studies involving 2,430 adult myopic eyes (with axial lengths >26.0 mm) that underwent uncomplicated cataract surgery with mono-focal IOL implantation were included. The network meta-analysis of 21 formulas showed that the top three AI-based formulas, as per the surface under the cumulative ranking curve (SUCRA) values, were XGBoost, Hill-RBF, and Kane. The three formulas had the lowest MedAE and were more accurate than traditional vergence formulas, such as SRK/T, Holladay 1, Holladay 2, Haigis, and Hoffer Q regarding MAE, percentage of eyes with PE within ±0.25, ±0.50, and ±1.00 D. Conclusions: The top AI-based formulas for calculating IOL power in highly myopic eyes were XGBoost, Hill-RBF, and Kane. They were significantly more accurate than traditional vergence formulas and ranked better than formulas with Wang-Koch AL modifications or newer generations of formulas such as Barrett and Olsen. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022335969.

Phosphoinositide 3-kinase as a therapeutic target in angiogenic disease.

Phosphoinositide 3-kinases (PI3Ks) generate lipids that control multitudinous intracellular cell signaling events which participate in cell survival and proliferation. In addition, PI3K signaling also contributes to metabolism, immunity, angiogenesis and cardiovascular homeostasis, and many diseases. The diverse actions of PI3K stem from the existence of their various isoforms and a variety of protein effectors. Hence, PI3K isoform-specific inhibitors have already achieved a wonderful effect on treating cancer. Herein, we summarize the molecular mechanism of PI3K inhibitors in preventing the permeability of vessels and neovascularization. Additionally, we briefly illustrate how PI3K signaling modulates blood vessel growth and discuss the different roles that PI3K isoforms play in angiogenesis.

Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.

The endoplasmic reticulum (ER) functions as a quality-control organelle for protein homeostasis, or "proteostasis". The protein quality control systems involve ER-associated degradation, protein chaperons, and autophagy. ER stress is activated when proteostasis is broken with an accumulation of misfolded and unfolded proteins in the ER. ER stress activates an adaptive unfolded protein response to restore proteostasis by initiating protein kinase R-like ER kinase, activating transcription factor 6, and inositol requiring enzyme 1. ER stress is multifaceted, and acts on aspects at the epigenetic level, including transcription and protein processing. Accumulated data indicates its key role in protein homeostasis and other diverse functions involved in various ocular diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, achromatopsia, cataracts, ocular tumors, ocular surface diseases, and myopia. This review summarizes the molecular mechanisms underlying the aforementioned ocular diseases from an ER stress perspective. Drugs (chemicals, neurotrophic factors, and nanoparticles), gene therapy, and stem cell therapy are used to treat ocular diseases by alleviating ER stress. We delineate the advancement of therapy targeting ER stress to provide new treatment strategies for ocular diseases.

A Modified Single-Armed Suture Technique for Traumatic Cyclodialysis Cleft with Vitreoretinal Injury.

Our aim was to assess the therapeutic efficacy of a modified single-arm suture technique on traumatic cyclodialysis cleft with vitreoretinal injury. The procedure involved fixing a detached ciliary body using a single-armed 10-0 polypropylene suture under the assistance of a 29-gauge needle. Patients with a traumatic cyclodialysis cleft combined with an anterior and posterior segment injury who underwent modified internal cyclopexy together with vitreoretinal surgery were enrolled in this study. Ultrasound biomicroscopy (UBM) was used to diagnose and evaluate the cyclodialysis and anterior segment injury. B-scan ultrasonography was performed to assess the condition of the vitreous, retina and choroid. The surgical time and successful rate for repairing the cyclodialysis cleft were recorded. Preoperative and postoperative best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were documented for assessment. The study included 20 eyes. The extent of the cyclodialysis cleft was from 30° to 360°. Besides a traumatic cyclodialysis cleft, the included cases also combined this with vitreous hemorrhages, retinal detachment, macular holes, choroid avulsion, and suprachoroidal hemorrhage. All the clefts were anatomically closed in one surgery. The average surgical time for fixing the cyclodialysis cleft was 2.68 ± 0.54 min/30° cleft. A significant improvement in LogMAR BCVA was observed from 2.94 ± 0.93 preoperatively to 1.81 ± 1.11 at the 6-month follow-up. IOP was elevated from 10.90 ± 6.18 mmHg preoperatively to 14.45 ± 2.35 mmHg at the 6-month follow-up. The modified single-armed suture technique was proved to be an effective method to fix the traumatic cyclodialysis cleft, which could facilitate the use of the procedure to repair chorioretinal disorders. It improved the BCVA and maintained the IOP with less postoperative complications.

The Epidemiology and Clinical Characteristics of Fungemia in a Tertiary Hospital in Southern China: A 6-Year Retrospective Study.

Knowledge of the epidemiology and clinical characteristics of fungemia in southern China is limited. We conducted a six-year retrospective descriptive study to analyze the epidemiological and clinical characteristics of fungemia at the largest tertiary hospital in Guangxi, southern China. Data were obtained from the laboratory registry of patients with fungemia between January 2014 and December 2019. Demographic characteristics, underlying medical conditions, and outcomes for each case were analyzed. A total of 455 patients with fungemia were identified. Unexpectedly, Talaromyces marneffei (T. marneffei) was the most frequently isolated agent causing fungemia in the region (149/475, 31.4%), and Candida albicans (C. albicans) was the most commonly isolated Candida spp. (100/475, 21.1%). We identified that more than 70% of talaromycosis fungemia developed in AIDS patients, whereas candidemia was most commonly associated with a history of recent surgery. Notably, the total mortality rate of fungemia and the mortality rate in patients with T. marneffei and Cryptococcus neoformans (C. neoformans) fungemia were significantly higher in HIV-uninfected patients than in HIV-infected patients. In conclusion, the clinical pattern of fungemia in Guangxi is different from that in previous studies. Our study may provide new guidance for the early diagnosis and prompt treatment of fungemia in similar geographic regions.

Comparison of clinical outcomes between cystotome-assisted prechop phacoemulsification surgery and femtosecond laser-assisted cataract surgery for hard nucleus cataracts.

BACKGROUND/OBJECTIVES: To compare the safety and efficacy of cystotome-assisted prechop phacoemulsification surgery (CAPPS) and femtosecond laser-assisted cataract surgery (FLACS) in patients with hard nucleus cataract. SUBJECTS/METHODS: Ninety-six eyes of 64 patients with grade IV hard nucleus cataract were assigned to 1 of the 2 groups (49 CAPPS and 47 FLACS). Follow-up visits were performed at 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year, and the outcome measures comprised ultrasound power, effective phacoemulsification time (EPT), corrected distance visual acuity (CDVA), endothelial cell density (ECD), corneal endothelium cell loss rate (ECL), central corneal thickness (CCT), and intraoperative and postoperative complications. RESULTS: The ultrasound power and EPT were lower in the CAPPS group (p = 0.03 and <0.0001, respectively). Patients in both groups gained better CDVA postoperatively. The ECD value decreased at each follow-up visit and did not return to the preoperative level; FLACS resulted in greater endothelial cell loss compared to CAPPS. CCT increased immediately after the surgery and decreased thereafter. The mean CCT value returned to the preoperative level 3 months postoperatively in the CAPPS group, while in the FLACS group, CCT value took 6 months to return to the preoperative level. Miosis was more likely to occur in the FLACS group. CONCLUSIONS: Due to its efficacy and cost-effectiveness, CAPPS is worth promoting and applying to clinical work in the future.

Pathologically high intraocular pressure disturbs normal iron homeostasis and leads to retinal ganglion cell ferroptosis in glaucoma.

Glaucoma can result in retinal ganglion cell (RGC) death and permanently damaged vision. Pathologically high intraocular pressure (ph-IOP) is the leading cause of damaged vision during glaucoma; however, controlling ph-IOP alone does not entirely prevent the loss of glaucomatous RGCs, and the underlying mechanism remains elusive. In this study, we reported an increase in ferric iron in patients with acute primary angle-closure glaucoma (the most typical glaucoma with ph-IOP damage) compared with the average population by analyzing free iron levels in peripheral serum. Thus, iron metabolism might be involved in regulating the injury of RGCs under ph-IOP. In vitro and in vivo studies confirmed that ph-IOP led to abnormal accumulation of ferrous iron in cells and retinas at 1-8 h post-injury and elevation of ferric iron in serum at 8 h post-injury. Nuclear receptor coactivator 4 (NCOA4)-mediated degradation of ferritin heavy polypeptide 1(FTH1) is essential to disrupt iron metabolism in the retina after ph-IOP injury. Furthermore, knockdown of Ncoa4 in vivo inhibited FTH1 degradation and reduced the retinal ferrous iron level. Elevated ferrous iron induced by ph-IOP led to a marked accumulation of pro-ferroptotic factors (lipid peroxidation and acyl CoA synthetase long-chain family member 4) and a depletion of anti-ferroptotic factors (glutathione, glutathione peroxidase 4, and nicotinamide adenine dinucleotide phosphate). These biochemical changes resulted in RGC ferroptosis. Deferiprone can pass through the blood-retinal barrier after oral administration and chelated abnormally elevated ferrous iron in the retina after ph-IOP injury, thus inhibiting RGC ferroptosis and protecting visual function. In conclusion, this study revealed the role of NCOA4-FTH1-mediated disturbance of iron metabolism and ferroptosis in RGCs during glaucoma. We demonstrate the protective effect of Deferiprone on RGCs via inhibition of ferroptosis, providing a research direction to understand and treat glaucoma via the iron homeostasis and ferroptosis pathways.

Correction of presbyopia. / 老视的矫治方法.

Presbyopia, a progressive visual difficulty caused by weakened physiological regulation, is one of the main causes of visual impairment in people over 40 years old. Currently, the main methods of correction of presbyopia include optical correction, surgical correction, and drug treatment, which can improve the visual nearness disorder to some extent. Optical correction is the most common way with advantages of safety, which can adjust the lens parameters at any time, while cause kinds of inconvenience in life by wearing and taking off glasses frequently. Surgical intervention, including corneal surgery, lens surgery and scleral surgery, with certain advantages and disadvantages in each operation style. New pharmaceutical agents are expected to be a new and effective method for the treatment of presbyopia, but it lacks multicenter randomized controlled trials and evidence-based medicine evidence to evaluate the safety and effectiveness.

GSK872 and necrostatin-1 protect retinal ganglion cells against necroptosis through inhibition of RIP1/RIP3/MLKL pathway in glutamate-induced retinal excitotoxic model of glaucoma.

BACKGROUND: Glaucoma, the major cause of irreversible blindness worldwide, is characterized by progressive degeneration of retinal ganglion cells (RGCs). Current treatments for glaucoma only slow or partially prevent the disease progression, failing to prevent RGCs death and visual field defects completely. Glutamate excitotoxicity via N-methyl-D-aspartic acid (NMDA) receptors plays a vital role in RGCs death in glaucoma, which is often accompanied by oxidative stress and NLRP3 inflammasome activation. However, the exact mechanisms remain unclear. METHODS: The glutamate-induced R28 cell excitotoxicity model and NMDA-induced mouse glaucoma model were established in this study. Cell counting kit-8, Hoechst 33342/PI dual staining and lactate dehydrogenase release assay were performed to evaluate cell viability. Annexin V-FITC/PI double staining was used to detect apoptosis and necrosis rate. Reactive oxygen species (ROS) and glutathione (GSH) were used to detect oxidative stress in R28 cells. Levels of proinflammatory cytokines were measured by qRT-PCR. Transmission electron microscopy (TEM) was used to detect necroptotic morphological changes in RGCs. Retinal RGCs numbers were detected by immunofluorescence. Hematoxylin and eosin staining was used to detect retinal morphological changes. The expression levels of RIP1, RIP3, MLKL and NLRP3 inflammasome-related proteins were measured by immunofluorescence and western blotting. RESULTS: We found that glutamate excitotoxicity induced necroptosis in RGCs through activation of the RIP1/RIP3/MLKL pathway in vivo and in vitro. Administration of the RIP3 inhibitor GSK872 and RIP1 inhibitor necrostatin-1 (Nec-1) prevented glutamate-induced RGCs loss, retinal damage, neuroinflammation, overproduction of ROS and a decrease in GSH. Furthermore, after suppression of the RIP1/RIP3/MLKL pathway by GSK872 and Nec-1, glutamate-induced upregulation of key proteins involved in NLRP3 inflammasome activation, including NLRP3, pro-caspase-1, cleaved-caspase-1, and interleukin-1ß (IL-1ß), was markedly inhibited. CONCLUSIONS: Our findings suggest that the RIP1/RIP3/MLKL pathway mediates necroptosis of RGCs and regulates NLRP3 inflammasome activation induced by glutamate excitotoxicity. Moreover, GSK872 and Nec-1 can protect RGCs from necroptosis and suppress NLRP3 inflammasome activation through inhibition of RIP1/RIP3/MLKL pathway, conferring a novel neuroprotective treatment for glaucoma.

Application of team-based learning to ophthalmology in China.

Objectives: The purpose of this study was to explore whether team-based learning (TBL) was more effective than traditional didactic lectures (TDLs) in improving medical students' problem-solving and study skills in the clinical course of ophthalmology. In addition, we were also concerned about Chinese students' satisfaction with TBL. Methods: Our study program involved 275 students of the 5-year clinical medicine program from Central South China University, of which 140 were enrolled in a modified TBL course. A questionnaire that included closed-ended and open-ended items was distributed to students immediately following the completion of the TBL session, and 108 valid questionnaires were collected. Descriptive statistics were used to analyze quantitative data. The effects of the TBL module on students' performance were measured between the groups using a one-way between-group analysis of variance (ANOVA) test by the individual readiness assurance test (IRAT), the group readiness assurance test (GRAT), and final examination scores (FESs), compared with a class without the TBL session. Results: With our modified TBL strategy, 140 students achieved a mean test score of 72.65 on test questions that assessed their knowledge of ophthalmology compared to 135 students who achieved a mean score of 70.8 using the TDL method (p = 0.3434). The performance in a pre-class quiz was significantly better in the GRAT compared to the IRAT. In comparison to the TDL session, the modified TBL was preferred and acceptable by most medical students. Conclusions: By applying the modified TBL to ophthalmology, students improved their performance, self-study, and teamwork, and their class engagement and satisfaction were enhanced. However, TBL should be further optimized and developed to enhance educational outcomes.

Risk factors and surgical outcomes for the concurrence of intraocular lens dislocation with vitreoretinal diseases. / äººå·¥æ™¶çŠ¶ä½“è„±ä½åˆå¹¶çŽ»ç’ƒä½“è§†ç½‘è†œç–¾ç— çš„å±é™©å› ç´ åŠæ‰‹æœ¯ç–—æ•ˆ.

OBJECTIVES: The weakness and dialysis of lens zonule after cataract surgery may lead to dislocation of intraocular lens (IOL). It has been shown that cataract surgery could induce or aggravate posterior vitreous detachment (PVD) due to postoperative inflammation and increased volume of vitreous cavity. PVD is associated with the occurrence of several vitreoretinal diseases, such as rhegmatogenous retinal detachment and macular hole. This study aims to explore risk factors for dislocation of IOL concurring with vitreoretinal disease, such as retinal detachment and macular hole, and to evaluate the efficacy and complications of surgical intervention for these abnormalities concurrently. METHODS: Ten patients (10 eyes) who diagnosed as rhegmatogenous retinal detachment, traumatic macular hole, high myopic macular hole, and combined with IOL dislocation at the Department of Ophthalmology of Xiangya Hospital from January 2004 to December 2020 were enrolled. The patients received vitreoretinal surgery and reposition of IOL by scleral suturing. Medical records were reviewed to figure out the time and type of IOL dislocation. Preoperative and 1 year of postoperative best corrected visual acuity, intraocular pressure, corneal endothelial density, and complications of surgical management were analyzed. RESULTS: Ten patients including 4 high myopia, 4 ocular contusion, and 2 who experienced IOL dislocation during the posterior capsulotomy were included in this study. Coexistence of IOL dislocation and vitreoretinal abnormalities occurred in patients with high myopia, ocular contusion, and capsulotomy. IOL dislocation happened in the vitreoretinal surgery in patients with high myopia or intraoperative capsulotomy. IOL dislocation occurred preoperatively in patients with ocular contusion. IOL capsular bag complex dislocation and out-of-the-bag IOL dislocation were found in 4 and 6 patients, respectively. Surgical relocation of dropped IOL and repair of vitreoretinal disease improved the best corrected visual acuity from preoperative 1.79±0.39 to postoperative 1.13±0.45 (P<0.001). The density of corneal endothelial cells in patients was lower than that before surgery [(1 806.40±181.20) cells/mm2 vs (1 914.00±182.22) cells/mm2, P<0.001]. There was no significant difference in intraocular pressure before and after surgery (P=0.099). Postoperative complications included high intraocular pressure and recurrent retinal detachment. CONCLUSIONS: Dislocation of IOL may be concurrent with vitreoretinal disease. High myopia, blunt contusion, and capsulectomy might be the risk factors for intraocular lens dislocation. The surgical technique used in the present study is successful in manipulating these disorders with optimal functional results and less severe complications.

Integrated analysis to reveal potential therapeutic targets and prognostic biomarkers of skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is a malignant tumor with high mortality rate in human, and its occurrence and development are jointly regulated by genes and the environment. However, the specific pathogenesis of SKCM is not completely understood. In recent years, an increasing number of studies have reported the important role of competing endogenous RNA (ceRNA) regulatory networks in various tumors; however, the complexity and specific biological effects of the ceRNA regulatory network of SKCM remain unclear. In the present study, we obtained a ceRNA regulatory network of long non-coding RNAs, microRNAs, and mRNAs related to the phosphatase and tensin homolog (PTEN) in SKCM and identified the potential diagnostic and prognostic markers related to SKCM. We extracted the above three types of RNA involved in SKCM from The Cancer Genome Atlas database. Through bioinformatics analysis, the OIP5-AS1-hsa-miR-186-5p/hsa-miR-616-3p/hsa-miR-135a-5p/hsa-miR-23b-3p/hsa-miR-374b-5p-PTPRC/IL7R/CD69 and MALAT1-hsa-miR-135a-5p/hsa-miR-23b-3p/hsa-miR-374b-5p-IL7R/CD69 ceRNA networks were found to be related to the prognosis of SKCM. Finally, we determined the OIP5-AS1-PTPRC/IL7R/CD69 and MALAT1-IL7R/CD69 axes in ceRNA as a clinical prognostic model using correlation and Cox regression analyses. Additionally, we explored the possible role of these two axes in affecting gene expression and immune microenvironment changes and the occurrence and development of SKCM through methylation and immune infiltration analyses. In summary, the ceRNA-based OIP5-AS1-PTPRC/IL7R/CD69 and MALAT1-IL7R/CD69 axes may be a novel and important approach for the diagnosis and prognosis of SKCM.

From Bench to Bed: The Current Genome Editing Therapies for Glaucoma.

Glaucoma is a group of optic neuropathies featured by degeneration of retinal ganglion cells and loss of their axons in the optic nerve. The only currently approved therapies focus on lowering intraocular pressure with medication and surgery. Over the previous few decades, technological advances and research progress regarding pathogenesis has brought glaucomatous gene therapy to the forefront. In this review, we discuss the three current genome editing methods and potential disease mechanisms of glaucoma. We further summarize different genome editing strategies that are being developed to target a number of glaucoma-related genes and pathways from four aspects including strategies to lower intraocular pressure, neuroprotection, RGC and optic nerve neuro-regeneration, and other strategies. In summary, genome therapy is a promising therapy for treating patients with glaucoma and has great potential to be widely applied in clinical practice.

Protective activity of tert-butylhydroquinone against oxidative stress and apoptosis induced by glutamate agonizts in R28 cells and mice retina.

Glutamate excitotoxicity can cause cell damage and apoptosis and play an important role in a variety of retinal diseases. Tertiary-butylhydroquinone (tBHQ) is an approved food-grade phenolic antioxidant with antioxidant activity in a variety of cells and tissues. We observed the protective effect of tBHQ on glutamatergic agonist-induced retina and explored its possible mechanism of action through in vitro cell experiments. The results showed that tBHQ had protective effects on NMDA-induced mouse retinal excitotoxicity and glutamate-induced excitotoxicity in rat retinal precursor cells (R28 cells). tBHQ reversed glutamate-induced apoptosis, production of intracellular reactive oxygen species, and reduction of mitochondrial membrane potential. Western blot analysis showed that tBHQ could increase the expression of procaspase-3, Bcl-2, AIF precursor, CAT, SOD2, Nrf2, NQO1, HO-1 and NF-κB in glutamate-treated cells, and decrease the expression of AIF cleavage products. Furthermore, we discovered that tBHQ activated müller glial cells. Based on these results, tBHQ may have antioxidant and anti-apoptotic properties, thus serving as a potential retinal protective agent. Its anti-oxidative stress effect was attributed to up-regulation of Nrf2, and its anti-apoptotic effect was related to its up-regulation of Bcl-2 expression and inhibition of mitochondria-dependent apoptosis.

Hyperglycemia induces retinal ganglion cell endoplasmic reticulum stress to the involvement of glaucoma in diabetic mice.

Glaucoma is a neurodegenerative disease leading to visual loss. Since glaucoma is associated with chronic renal diseases (RDs) their rate is higher in patients with RDs, and end-stage RDs (ESRDs) than in the general population and kidney transplant recipients. OBJECTIVE: To explore the molecular mechanism of diabetic internal environment in regulating the endoplasmic reticulum stress of the retinal ganglion cells (RGCs). METHODS: Thirty-six SPF grade type 2 diabetes models were divided into 3 groups: Diabetes mellitus (DM), DM + glaucoma and 4-phenylbutyric acid-DM (4-PBA-DM) + glaucoma group. C57BL6 mice of the same week age were taken as the negative control (NC) group. The morphology of RGCs and their axon in the 4 groups were labeled by fluorescent reactive dye Dil. The apoptosis situation of RGCs was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The protein expression values of RTN4IP1, Protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2A (eIF2a) and X-box-binding Protein 1 (XBP1) were determined by western blot. The relative mRNA levels of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), Caspase12 and Bax were determined by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Glaucoma promotes the apoptosis of RGCs. The protein expression values of RTN4IP1, PERK and XBP1 in DM mouse models with glaucoma were much higher compared to only DM mouse models. Further injection of endoplasmic reticulum stress inhibitor 4-PBA decreased the expression values. The relative mRNA levels of CHOP, Cysteine aspartic acid specific protease12 (Caspase12) and BCL2-associated X protein (Bax) in DM + glaucoma were significantly higher compared to those in DM group. Further injection of endoplasmic reticulum stress inhibitor 4-PBA decreased the mRNA levels. CONCLUSION: Endoplasmic reticulum stress (ERS) is the underlying cause of glaucoma, which could promote the apoptosis of RGCs in diabetic mice.

Two-Year Follow-Up of Clinical Efficacy of Femtosecond Laser, Modified Capsular Tension Ring, and Iris Hook-Assisted Surgical Treatment of Lens Subluxation in Patients with Elevated Intraocular Pressure.

Purpose: To evaluate the outcomes of femtosecond laser, modified capsular tension ring, and iris hook-assisted surgical treatment of lens subluxation in patients with elevated intraocular pressure (IOP). Methods: Fifteen patients with lens subluxation and elevated IOP were enrolled in this study. All patients underwent femtosecond-laser-assisted cataract surgery/phacoemulsification/intraocular lens implantation/modified capsular tension ring (MCTR) implantation with iris hook assistance. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), IOP, number of glaucoma medication complications, endothelial cell density (ECD), and tilt of the lens were recorded before and after surgery. All patients were observed for 24 months postoperatively. Results: UCVA and BCVA increased significantly at 1 month, 6 months, 12 months, and 24 months, compared with preoperative UCVA and BCVA (P < 0.001). IOP significantly decreased at 1 month, 3 months, 6 months, 12 months, and 24 months, compared with preoperative IOP (P < 0.001). 3 patients received glaucoma medications to control IOP after surgery. All medications were discontinued at 3 months postoperatively. Conjunctival redness or hemorrhage was observed in 11 patients (73.3%); transient corneal edema was observed in 3 patients (20.0%); and posterior capsule opacification occurred in 1 patient (6.67%). The ECD and tilt of the lens are within an acceptable range. Conclusion: The combined use of a femtosecond laser, MCTR, and iris hooks is an effective and safe method for treating patients with lens subluxation and elevated IOP.

PTB: Not just a polypyrimidine tract-binding protein.

Polypyrimidine tract-binding protein (PTB), as a member of the heterogeneous nuclear ribonucleoprotein family, functions by rapidly shuttling between the nucleus and the cytoplasm. PTB is involved in the alternative splicing of pre-messenger RNA (mRNA) and almost all steps of mRNA metabolism. PTB regulation is organ-specific; brain- or muscle-specific microRNAs and long noncoding RNAs partially contribute to regulating PTB, thereby modulating many physiological and pathological processes, such as embryonic development, cell development, spermatogenesis, and neuron growth and differentiation. Previous studies have shown that PTB knockout can inhibit tumorigenesis and development. The knockout of PTB in glial cells can be reprogrammed into functional neurons, which shows great promise in the field of nerve regeneration but is controversial.