A New Technique of Sterile Polyethylene Instrument Cover as Temporary Corneal Patch to Reconstruct Anterior Chamber in Penetrating Keratoplasty Combined with Intraocular Surgery.

PURPOSE: Complications such as explosive choroidal hemorrhage, residual cortex, and capsule rupture often occur during intraocular surgery combined with penetrating keratoplasty (PKP) due to poor maintenance of the anterior chamber. To address these challenges, we have innovatively utilized a sterile polyethylene instrument cover to temporarily reconstruct the anterior chamber. METHODS: In this report, we describe a technique where a 'temporary corneal patch' was created from a sterile instrument cover, using a trephine to ensure a diameter approximately 1-2 mm wider than the corneal bed or perforation. This patch was then sutured into the host corneal bed or the perforation with 10-0 nylon sutures during intraocular surgery combined with PKP. Each case was evaluated for surgical efficacy and complications. RESULTS: We successfully applied this technique in three cases of combined corneal transplantation surgery. In two cases, PKP, phacoemulsification, and intraocular lens implantation were successfully performed. In the third case, PKP, vitrectomy, and other intraocular procedures were performed. No intraoperative or postoperative complications were observed. CONCLUSION: The use of a sterile polyethylene material as a temporary corneal patch for anterior chamber reconstruction represents a safe, effective, and cost-efficient approach for intraocular surgery combined with PKP or posterior segment surgery as a keratoprosthesis.

Rapamycin antagonizes angiogenesis and lymphangiogenesis through myeloid-derived suppressor cells in corneal transplantation.

Rapamycin is an immunosuppressive drug that is widely used in the postsurgery management of transplantation. To date, the mechanism by which rapamycin reduces posttransplant neovascularization has not been fully understood. Given the original avascularity and immune privilege of the cornea, corneal transplantation is considered as an ideal model to investigate neovascularization and its effects on allograft rejection. Previously, we found that myeloid-derived suppressor cells (MDSC) prolong corneal allograft survival through suppression of angiogenesis and lymphangiogenesis. Here, we show that depletion of MDSC abolished rapamycin-mediated suppression of neovascularization and elongation of corneal allograft survival. RNA-sequencing analysis revealed that rapamycin dramatically enhanced the expression of arginase 1 (Arg1). Furthermore, an Arg1 inhibitor also completely abolished the rapamycin-mediated beneficial effects after corneal transplantation. Taken together, these findings indicate that MDSC and elevated Arg1 activity are essential for the immunosuppressive and antiangiogenic functions of rapamycin.

Continuous voriconazole lavage in managing moderate and severe fungal keratitis: a randomized controlled trial.

PURPOSE: To assess the effectiveness and safety of continuous lavage with 1% voriconazole (CL) for moderate and severe fungal keratitis. METHODS: Thirty-one patients were randomized to receive topical eye drops either alone (T) or combined with continuous 1% voriconazole lavage (CL-T). The primary outcome was the cure rate at 3 months. The secondary outcomes were the 6-day efficacy, 3-day infiltration size and depth, hypopyon height, central corneal thickness (CCT), epithelial defect size, and subject feelings and clinical signs assessment scores. RESULTS: At 3 months, the cure rate was comparable between the groups in patients with moderate fungal keratitis (66.7% vs. 62.5%, P = 0.60). However, among severe cases, 4 cases (44.4%) in the CL-T group healed successfully, while none in the T group; this difference was not significant (P = 0.08), although it was very close to 0.05. This may be related to the small sample size. After 6 days, the percentage of patients with "worsened" ulcers in the CL-T group was lower than that in the T group (0% vs. 31%, P = 0.043). The infiltration size, infiltration depth, and hypopyon height in the CL-T group were smaller than those in the T group after 3 days (all P < 0.05). There was no difference in CCT, epithelial defect size, subject feelings scores, or clinical signs scores between groups. CONCLUSION: These outcomes suggest that CL is an effective and safe adjuvant method for controlling the progression of moderate and severe fungal keratitis. TRIAL REGISTRATION NUMBER: ChiCTR2100050565.

Combined Phacovitrectomy with Metallic Intraocular Foreign Body Removal through Corneal Incision Using A Novel "Magnetic Conduction" Technique.

PURPOSE: To describe a "magnetic conduction" technique for the removal of metallic intraocular foreign bodies (IOFBs) in the posterior segment combined with cataract extraction and pars plana vitrectomy and to report its outcomes. METHODS: We retrospectively analyzed the data of 42 eyes of 42 patients with posterior metallic IOFBs between April 2020 and February 2022. In all patients, cataract extraction was combined with pars plana vitrectomy. With an external magnet, the IOFBs were captured by a magnetized vitrectomy cutter, delivered to the anterior chamber, and then extracted through a corneal phacoemulsification incision. RESULTS: All patients were men, with a mean age of 45.6 ± 10.7 years. The mean size of the IOFBs was 3.5 ± 1.7 mm (range, 1.5-8.9 mm) in their longest dimension. A final best-corrected visual acuity of 20/200 or better was noted in 24 of 42 patients (57.1%). Postoperatively, recurrent retinal detachment was seen in three eyes. There were no other intraoperative or postoperative complications. CONCLUSION: The "magnetic conduction" technique combined with phacovitrectomy is a safe and feasible approach to removing IOFBs in the posterior segment.

Evaluation and correlation analysis of ocular surface disorders and quality of life in autoimmune rheumatic diseases: a cross-sectional study.

OBJECTIVE: This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients. METHODS: Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman's analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions. RESULTS: The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality. CONCLUSION: Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients.

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.

Insights into the spontaneous multi-scale supramolecular assembly in an ionic liquid-based extraction system.

Herein, we report a four-step mechanism for the spontaneous multi-scale supramolecular assembly (MSSA) process in a two-phase system concerning an ionic liquid (IL). The complex ions, elementary building blocks (EBBs), [EBB]n clusters and macroscopic assembly (MA) sphere are formed step by step. The porous large-sized [EBB]n clusters in the glassy state can hardly stay in the IL phase and they transfer to the IL-water interface due to both electroneutrality and amphiphilicity. Then, the clusters undergo random collision in the interface driven by the Marangoni effect and capillary force thereafter. Finally, a single MA sphere can be formed owing to supramolecular interactions. To our knowledge, this is the first example realizing spontaneous whole-process supramolecular assembly covering microscopic, mesoscopic and macroscopic scales in extraction systems. The concept of multi-scale selectivity (MSS) is therefore suggested and its mechanism is revealed. The selective separation and solidification of metal ions can be realized in a MSSA-based extraction system depending on MSS. In addition, insights into the physicochemical characteristics of ILs from microscopic, mesoscopic to macroscopic scales are provided, and especially, the solvation effect of ILs on the large-sized clusters leading to the phase-splitting is examined. It is quite important that the polarization of uranyl in its complex, the growing of uranyl clusters in an IL as well as the glassy material of uranyl are investigated systematically on the basis of both experiment and theoretical calculations in this work.

Myeloid-derived suppressor cells improve corneal graft survival through suppressing angiogenesis and lymphangiogenesis.

Myeloid-derived suppressor cells (MDSC) are one of the major negative regulators of immune responses during many pathological conditions such as cancer and transplantation. Emerging evidence indicates that MDSC also contribute to tumor progression through their pro-angiogenic activity in addition to immunosuppressive function. However, virtually nothing is known about the role of MDSC in the regulation of neovascularization after transplantation. Here we showed that antibody-mediated depletion of MDSC in mice led to robust growth of blood and lymphatic neovessels and rapid allograft rejection after corneal penetrating keratoplasty. In contrast, adoptive transfer of ex vivo generated MDSC from cytokine-treated bone marrow cells (evMDSC) suppressed neovascularization and prolonged corneal allograft survival in an inducible nitric oxide synthase (iNOS)-dependent manner. Mechanistically, compared to naïve MDSC control, evMDSC have increased expression of an anti-angiogenic factor thrombospondin 1 (Tsp-1) and decreased expression of two critical pro-angiogenic factors, vascular endothelial growth factor A (VEGF-A), and VEGF-C. These findings demonstrate MDSC as a critical anti-angiogenic regulator during transplantation. Our study also indicates that evMDSC are a valuable candidate agent for development of novel cell therapy to improve allograft survival after transplantation.

Complexation of Cyclic Glutarimidedioxime with Cerium: Surrogating for Redox Behavior of Plutonium.

The complexation of cerium with glutarimidedioxime (H2L) was studied by potentiometry, ESI-mass spectrometry, and cyclic voltammetry. Crystallization of [CeIV(HL)3]+ from Ce3+ starting reactant indicated spontaneous complexation-driven oxidation. In aqueous solution, Ce3+ ions form three successive complexes, Ce(HL)2+, Ce(HL)2+, and Ce(HL)3 (where HL- stands for the singly deprotonated ligand). The interactions of glutarimidedioxime with metal ions are dominantly electrostatic in nature, and the stability constants of the complexes are correlated to the charge density of metal ions. Extrapolations of predicted stability constant (log ß) values were made from plotting effective charge and the ionic radius of the metal ion for Pu3+ and Pu4+. The stability constants of PuIV(HL)3+ and PuIII(HL)2+ are estimated to be 27.74 and 19.75, respectively. The differences of stability constants mean that glutarimidedioxime selectively binds Pu4+ over Pu3+ by a factor of about 8 orders of magnitude, suggesting Pu4+ would be stabilized by chelation with glutarimidedioxime. The mechanism of reduction of Pu4+ to Pu3+ in acidic solution is explained by decomposition of glutarimidedioxime through acid hydrolysis rather than a chelation-driven mechanism.

Evaluation of optical quality in pterygium patients with a new modified sutureless and glue-free method.

BACKGROUND: Modified sutureless and glue-free method is an effective and novel surgical approach for pterygium. We aim to evaluate optical quality in pterygium treated with the new method and investigate the clinical application of the Optical Quality Analysis System (OQAS) and Anterior segment optical coherence tomography (AS-OCT) to evaluate the pterygium surgery. METHODS: A total of 52 eyes of 52 patients with pterygium were randomly divided into 2 groups. After surgical excision, the bare sclera was placed with a tight fit limbal conjunctival autograft fixed via the modified sutureless and glue-free method in group 1 (26 eyes) and conventional sutures in group 2 (26 eyes). Objective scattering index (OSI), modulation transfer function (MTF) and Strehl ratio (SR) were measured using OQAS in both groups during the perioperative period. Pterygium diameter was measured on AS-OCT. Ocular surface disease index (OSDI) questionnaire also was used. RESULTS: The group 1 had significantly lower mean OSI, higher mean MTF, and higher mean SR at 1 month and 3 months after surgery (p < 0.05). The group 1 had significantly lower mean OSDI at 1 month (p < 0.05), while was similar to group 2 at 3 months (p > 0.05). Pterygium diameter positively correlated with OSI (r = 0.528, p < 0.001), while it negatively correlated with MTF (r = - 0.501, p < 0.001) and SR (r = - 0.174, p = 0.217) before operation. CONCLUSIONS: The modified sutureless and glue-free method might be more advantageous in improving the optical quality during early postoperative recovery times and pterygium diameter affected optical quality. OQAS can be reliably used to evaluate postoperative outcomes.

DJ-1/PARK7 inhibits high glucose-induced oxidative stress to prevent retinal pericyte apoptosis via the PI3K/AKT/mTOR signaling pathway.

Reactive oxygen species (ROS) act through multiple pathways to induce apoptosis of retinal capillary pericytes, which is an early marker and the primary cause of the progression of diabetic retinopathy. However, the specific molecular mechanisms behind ROS-induced retinal capillary pericyte loss in diabetic retinopathy remains elusive. In this study, we investigated the molecular regulation and effects of DJ-1/PARK7 on oxidative stress and injury of rat retinal pericytes (RRPs). To perform the research, RRPs were isolated from rat retina and cultured in medium with for 2 days: control group (5.6 mM glucose), high glucose group (30 mM glucose), hypertonic group (5.6 mM glucose + 24.4 mM mannitol). We found decreased expression of DJ-1 and increased apoptosis of RRPs in high glucose group. To further study the role of DJ-1, four groups were divided as follows: normal control group (5.6 mM glucose), high glucose (30 mM glucose), empty vector control group (pcDNA3.1,30 mM glucose), DJ-1 overexpression group (pcDNA3.1-myc-DJ-1,30 mM glucose). DJ-1, P53, p-P53, cleaved caspase-3, manganese superoxide dismutase (MnSOD), catalase (CAT) and PI3K/Akt/mTOR signaling pathway in each group was detected by Western Blot. RRPs apoptosis was detected by Terminal-deoxynucleoitidyl Transferase mediated Nick End Labeling (TUNEL) and 4'6- diamidino-2-phenylindole (DAPI). Mitochondrial function was detected by jc-1 and fluorescent probes DCFH-DA was used to determine reactive oxygen species (ROS). We found that high glucose (30 mM) lasting two days can induce significant apoptosis of RRPs, increase ROS production and expressions of p-p53 and active caspase-3, impair mitochondrial function, decrease the activities of MnSOD and CAT, and decrease expression of DJ-1, p-AKT and p-mTOR. In contrast, DJ-1/PARK7 overexpression significantly increases expression of DJ-1, p-AKT and p-mTOR, increases expression and activities of MnSOD and CAT, improves mitochondrial function, decreases expression of apoptotic gene protein p-p53 and active caspase-3, reduces ROS production and reduces the apoptotic rate of RRPs induced by high glucose. These results suggest that DJ-1 may play a role in protecting RRPs from high glucose induced-oxidative injury. DJ-1 might improve mitochondrial function, inhibit ROS production and enhance antioxidant capacity to reduce apoptosis of retinal pericytes through the PI3K/AKT/mTOR signaling pathway which may be related to early pathogenesis of diabetic retinopathy.

Complexation of Lanthanides with N, N, N', N'-Tetramethylamide Derivatives of Bipyridinedicarboxylic Acid and Phenanthrolinedicarboxylic Acid: Thermodynamics and Coordination Modes.

The thermodynamics of Nd(III) and Eu(III) complexes with N, N, N', N'-tetramethyl-2,2'-bipyridine-6,6'-dicarboxamide (TMBiPDA) and N, N, N', N'-tetramethyl-1,10-phenanthroline-2,9-dicarboxamide (TMPhenDA) in CH3OH/10%(v)H2O solutions were studied. Stability constants and enthalpies of complexation were determined by absorption spectrophotometry, luminescence, and calorimetry. The stability constants of corresponding lanthanide complexes decrease in the order of TMPhenDA > TMBiPDA, while those of the corresponding ligand complexes with lanthanides decrease in the order of Nd(III) > Eu(III). The stepwise reactions for all 1:1 complexes as well as for the 1:2 Nd(III) complexes are driven by both enthalpy and entropy, while those for the 1:2 Eu(III) complexes are driven by entropy. The stronger affinity of TMPhenDA to Nd(III) and Eu(III) than that of TMBiPDA is predominantly arisen from its high preorganization. The spectra of the complexes in solutions are similar, implying that Nd(III) and Eu(III) coordinate with the two ligands in the same mode, which have been validated by 1H and 13C NMR titrations using La(III) as lanthanide tracer. The luminescence lifetimes of the Eu(III) complexes with TMBiPDA and TMPhenDA were evaluated by TRLFS. Structures of Nd(III)/TMPhenDA and Eu(III)/TMPhenDA complexes, identified by single-crystal X-ray diffractometry, show that ligand coordinates to metal in a tetradentate mode via two aromatic N-donors and two amide O-donors, and the central cation (Nd(III) or Eu(III)) is 10-coordinated by two whole TMPhenDA and two solvent (water or methanol) molecules. The M-O bond distances are almost identical, while the Nd-N bond distance is shorter than the Eu-O bond.

Long-term outcome of scleral-fixated intraocular lens implantation without conjunctival peritomies and sclerotomy in ocular trauma patients.

BACKGROUND: To investigate the long-term outcomes and complications of scleral-fixated intraocular lens (SFIOL) implantation without conjunctival peritomies and sclerotomy in patients with a history of ocular trauma with inadequate capsular support during primary pars plana vitrectomy or silicone oil removal. METHODS: Records of ocular trauma patients who underwent implantation of SFIOL without conjunctival peritomies and sclerotomy during primary pars plana vitrectomy or silicone oil removal. RESULTS: Sixty-nine eyes of 69 patients were included in this study. The median follow-up period was 34 months (range, 6-99 months). The average patient age at the time of surgery was 44 years old (range, 4-80 years). At the end of follow-up, the preoperative mean of best corrected visual acuity (BCVA) was 0.79 ± 0.86 log of the minimum angle of resolution (logMAR), which improved 0.20 ± 0.26 logMAR postoperatively (P = 0.01). BCVA improved or remained unchanged in 64 eyes (92.8%), VA decreased two lines in five eyes (7.2%). Early postoperative complications included transient corneal edema in seven eyes (10.1%), minor vitreous hemorrhage in four eyes (5.8%), transient elevated intraocular pressure (IOP) in one eye (1.4%), and hypotony in three eyes (4.3%). Late postoperative complications included persistent elevated IOP in five eyes (7.2%), epiretinal membrane formation in three eyes (4.3%), and cystoid macular edema noted in one eye (1.4%). CONCLUSIONS: Use of a scleral-fixated intraocular lens implantation without conjunctival peritomies and sclerotomy in ocular trauma patients during either primary pars plana vitrectomy or second silicone oil removal is a valuable approach for the management of traumatic aphakia in the absence of capsular support.

Effectiveness of flipped classroom combined with team-, case-, lecture- and evidence-based learning on ophthalmology teaching for eight-year program students.

BACKGROUND: This study aimed to investigate the benefits and challenges of the flipped classroom combined with team-, case-, lecture- and evidence-based learning (FC-TCLEBL) for ophthalmology teaching for eight-year program students. METHODS: FC-TCLEBL and the traditional lecture-based classroom (LBC) were compared based on student and teacher feedback questionnaires, student learning burden, and scores on standardized tests as well as their effects on the abilities of clinical thinking, scientific research, active-learning, practical application, humanistic care and communication with patients. RESULTS: Both the students and teachers were more satisfied with the FC-TCLEBL model. More students in the FC-TCLEBL group agreed that the course helped them to develop skills in creative thinking, problem solving, and teamwork. Students in the FC-TCLEBL group spent significantly more time preparing for class than those in the LBC group, but the time spent on review was significantly lower in the FC-TCLEBL group. The students from the FC-TCLEBL group performed better in a post-test on diabetic retinopathy (DR) as compared to the LBC group. CONCLUSIONS: FC-TCLEBL teaching model is effective and suitable for ophthalmology teaching.

Effects of antioxidant gene therapy on the development of diabetic retinopathy and the metabolic memory phenomenon.

PURPOSE: The purpose of this study was to determine the therapeutic effect and mechanism of AAV-MnSOD by intravitreal injection on diabetic retinopathy (DRP) and the metabolic memory phenomenon. METHODS: The effect of hyperglycemia and metabolic memory on the thickness of basement membrane, ratio of pericyte area and cross-sectional area of capillary vessels in the nerve fiber layer and outer plexiform layer; retinal capillary cell apoptosis; number of acellular capillaries and activities of retinal MnSOD and catalase were examined and compared with intravitreal injection of AAV-MnSOD by transmission electron microscopy, TUNEL assay, ELISA, and immunohistochemistry. RESULTS: Hyperglycemia increased the thickness of capillary basement membranes in the nerve fiber layer and outer plexiform layer, decreased the ratio of pericyte area and cross-sectional area of capillary vessels, increased numbers of acellular capillaries and apoptosis of retinal capillary cells, and decreased activities of retinal MnSOD and catalase. Termination of hyperglycemia cannot reverse pathological changes listed above. Intra-vitreal injection of AAV-MnSOD dramatically elevated the level and activities of retinal MnSOD and catalase, and effectively prevented the progression of DRP and the metabolic memory phenomenon. CONCLUSIONS: Increasing reactive oxygen species concentration and continuous decreasing of antioxidant enzyme activity play important roles in DRP and the metabolic memory phenomenon. AAV-MnSOD gene therapy provides a promising strategy to inhibit this blinding disease.

Severe primary ocular surface involvement in Behcet disease.

PURPOSE: Behcet disease (BD) is a chronic, relapsing inflammatory disorder of unknown etiology characterized by obstructive vasculitis. Ocular surface involvement is a less frequent anterior segment finding. We report a patient with BD whose ocular presentation was severe surface involvement. CASE REPORT: A 26-year-old Chinese woman, who was diagnosed as having BD by a dermatologist because of oral and genital ulceration and erythema nodosum in the upper extremities 1 month ago, presented with dry eye syndrome, corneal ulceration, and conjunctival lesions. Both clinical and confocal microscope examination revealed bilateral severe inflammatory ocular surface disease. However, she did not have the common clinical ocular manifestations such as iridocyclitis, vitritis, retinal perivasculitis, or retinitis for BD. In addition to oral methylprednisolone and thalidomide, topical 1% prednisolone acetate ophthalmic suspension, tacrolimus ophthalmic suspension, and artificial tears were used. We observed for the first time histopathological changes of the eyelid in BD by confocal microscopy. CONCLUSIONS: Ocular surface lesions should be noted as an uncommon but possible manifestation of BD. Such severe ocular surface lesions without uveitis require a thorough medical history, dermatological examination, and serological testing to arrive at a diagnosis of BD. Accordingly, routine examination of the ocular surface is recommended in patients with BD, and BD should be included in a list of differential diagnoses for patients with ocular surface lesions.

Epigenetic mechanisms in the pathogenesis of diabetic retinopathy.

Diabetic retinopathy (DR), which arises as a result of an increasing incidence of diabetes mellitus, has gradually become a common disease. Due to its complex pathogenesis, the treatment means of DR are very limited. The findings of several studies have shown that instituting tight glycemic control in diabetic patients does not immediately benefit the progression of retinopathy, and the benefits of good control persist beyond the period of good glycemic control. This has led to the concept of persistent epigenetic changes. Epigenetics has now become an increasingly important area of biomedical research. Recently, important roles of various epigenetic mechanisms have been identified in the pathogenesis of diabetes and its complications. The aim of this review is to provide an overview of the epigenetics and epigenetic mechanisms in diabetes and diabetes complications, and the focus is on the emerging evidence for aberrant epigenetic mechanisms in DR.

DJ-1 regulates mitochondrial function and promotes retinal ganglion cell survival under high glucose-induced oxidative stress.

Purpose: This study aimed to investigate the antioxidative and neuroprotective effects of DJ-1 in mitigating retinal ganglion cell (RGC) damage induced by high glucose (HG). Methods: A diabetic mouse model and an HG-induced R28 cell model were employed for loss- and gain-of-function experiments. The expression levels of apoptosis and oxidative stress-related factors, including Bax, Bcl-2, caspase3, Catalase, MnSOD, GCLC, Cyto c, and GPx-1/2, were assessed in both animal and cell models using Western blotting. Retinal structure and function were evaluated through HE staining, electroretinogram, and RGC counting. Mitochondrial function and apoptosis were determined using JC-1 and TUNEL staining, and reactive oxygen species (ROS) measurement. Results: In the mouse model, hyperglycemia resulted in reduced retinal DJ-1 expression, retinal structural and functional damage, disrupted redox protein profiles, and mitochondrial dysfunction. Elevated glucose levels induced mitochondrial impairment, ROS generation, abnormal protein expression, and apoptosis in R28 cells. Augmenting DJ-1 expression demonstrated a restoration of mitochondrial homeostasis and alleviated diabetes-induced morphological and functional impairments both in vivo and in vitro. Conclusion: This study provides novel insights into the regulatory role of DJ-1 in mitochondrial dynamics, suggesting a potential avenue for enhancing RGC survival in diabetic retinopathy.

IL-22/IL-22RA1 Promotes Human Tenon's Capsule Fibroblasts Proliferation and Regulates Fibrosis Through STAT3 Signaling Pathway.

Purpose: Although it is now understood that most antiglaucoma surgeries fail because of scarring of the filtering tract, the underlying mechanism remains to be elucidated. The present study investigated the mechanism by which the interleukin (IL)-22/IL-22 receptor alpha 1 (IL-22RA1) signaling pathway regulates scar formation in glaucoma patients. Method: A total of 31 glaucoma patients who underwent trabeculectomy surgery with uncontrollable intraocular pressure because of scarring and 19 strabismus patients as the control patient group were included in the present study. ELISA was performed to measure the content of IL-22 in peripheral blood. Serum from patients was used to incubate human Tenon's capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and Western blot were performed to determine IL-22RA1 mRNA and protein expression levels. Flow cytometry was performed to assess the cell cycle distribution and the Cell Counting Kit-8 assay was used to analyze cell proliferation. Results: The ELISA assay revealed that the serum IL-22 level of glaucoma patients was significantly higher than the healthy group (29.80 ± 5.1 ng/µL vs. 5.21 ± 0.9 ng/µL). After incubation with patient serum, the proliferation and activation of human Tenon fibroblasts (HTFs) were promoted. IL-22 mediated the biological function of HTFs via directly binding IL-22RA1. Moreover, transfection of the siR-IL-22RA1 or IL-22RA1 gene resulted in significant antifibrosis or profibrosis in HTFs. When a signal transducer and activator of transcription (STAT) 3 inhibitor (BAY) was introduced to the IL-22RA1 overexpression group, IL-22-induced proliferation was reduced in HTFs. Additionally, glaucoma patients had increased levels of IL-22 expression following surgery. Conclusions: The IL-22/IL-22RA1/STAT3 signaling pathway promoted fibroblast cell proliferation and alpha-smooth muscle actin, potentially regulating fibrosis in glaucoma filtration tracts. Our results provide hitherto undocumented insights into the pathophysiology of postoperative scarring.