Using Smartphone Chatbot for Postoperative Care after Intravitreal Injection during COVID-19 Period: A Retrospective Cohort Study.

BACKGROUND: During COVID-19 pandemic period, it was difficult for the patients regular and scheduled follow-up in outpatient department, especially when lock-down. However, early detection of patients with initial infection or other serious conditions after ocular surgeries, such as intravitreous injection (IVI) for age-related macular degeneration (AMD). OBJECTIVE: We accessed a postoperative care chatbot system (PCCS) in smartphone for patients to self-report postoperative symptoms/signs with an instant bidirectional feedback system. METHODS: During the COVID-19 level 3 epidemic alert in July 2021 in Taiwan, the PCCS alerted the patient to report and grade six ocular symptoms/signs associated with ocular inflammation or retinal detachment. Patients used the PCCS for 7 days postoperatively to assess their symptoms/signs per day after receiving an alert. The data automatically collected using a cloud computer system judged the grade and sent messages to medical staff for further medical assistance. User's satisfaction questionnaire was collected on the 7th day. RESULTS: One hundred and eighty-five patients participated in this study. There were 26 reports (3.03%) of symptom grade deterioration (increased blurred vision, eye swelling, nausea, and floater/flash) in 12 patients (6.5%). No gender difference for the earlier medical consultation. One case occurred endophthalmitis and improved after 2 times prompt IVI antibiotics. 87% of patients were satisfied or very satisfied to communicate their symptoms instantly with the app, willing to use it again and considered it could improve quality of care. The incidence of earlier medical consultation is 3.8% (7/185) and the incidence of endophthalmitis is 0.5% (1/185). CONCLUSIONS: The chatbot system, designed for self-reporting postoperative symptoms and providing instant bidirectional feedback on smartphones, could be beneficial for enhancing early medical consultation without gender differences in AMD patients who receiving intravitreal injections. It achieves satisfactory response from patients.

Miro1 improves the exogenous engraftment efficiency and therapeutic potential of mitochondria transfer using Wharton's jelly mesenchymal stem cells.

Mitochondria are important for maintaining cellular energy metabolism and regulating cellular senescence. Mitochondrial DNA (mtDNA) encodes subunits of the OXPHOS complexes which are essential for cellular respiration and energy production. Meanwhile, mtDNA variants have been associated with the pathogenesis of neurodegenerative diseases, including MELAS, for which no effective treatment has been developed. To alleviate the pathological conditions involved in mitochondrial disorders, mitochondria transfer therapy has shown promise. Wharton's jelly mesenchymal stem cells (WJMSCs) have been identified as suitable mitochondria donors for mitochondria-defective cells, wherein mitochondrial functions can be rescued. Miro1 participates in mitochondria trafficking by anchoring mitochondria to microtubules. In this study, we identified Miro1 over-expression as a factor that could help to enhance the efficiency of mitochondrial delivery. More specifically, we reveal that Miro1 over-expressed WJMSCs significantly improved intercellular communications, cell proliferation rates, and mitochondrial membrane potential, while restoring mitochondrial bioenergetics in mitochondria-defective fibroblasts. Furthermore, Miro1 over-expressed WJMSCs decreased rates of induced apoptosis and ROS production in MELAS fibroblasts; although, Miro1 over-expression did not rescue mtDNA mutation ratios nor mitochondrial biogenesis. This study presents a potentially novel therapeutic strategy for treating mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and other diseases associated with dysfunctional mitochondria, while the pathophysiological relevance of our results should be further verified by animal models and clinical studies.

Ultraviolet A at levels experienced outdoors suppresses transforming growth factor-beta signaling and collagen production in human scleral fibroblasts.

Previous studies have highlighted the importance of outdoor time in reducing the risk of myopia progression. Although ultraviolet A (UVA) radiation dominates in terms of energy with respect to the UV radiation reaching the Earth's surface, its effects on the exposed anterior sclera have not been well studied. This study was designed to investigate the UVA-induced biological effects at peak sunlight levels in human scleral fibroblasts (HSFs). Using next-generation sequencing (NGS), we analyzed the differentially expressed genes (DEGs) in UVA-treated and normal HSFs. Further, we then identified the functions and key regulators of the DEGs using bioinformatics analysis, and verified the effects of UVA on gene and protein expression in HSFs using real-time PCR, western blotting, and immunofluorescence imaging. The highest level of solar UVA (365 nm) was 3.4 ± 0.18 (mW/cm2). The results from the functional analysis of the DEGs were related to structural changes in the extracellular matrix (ECM) and protein metabolism. Transforming growth factor-ß1 (TGF-ß1) and Smad3 were predicted to be potential upstream regulators, associated with ECM organization. Exposure to a single wavelength of UVA (365 nm, 3 mW/cm2) for 1 h for 5 consecutive days induced the downregulation of the mRNA of ECM genes including COL1A1, COL3A1, COL5A1, VCAN and collagen I protein in HSF. UVA downregulated Smad3 protein and reduced TGF-ß-induced collagen I protein production following UVA exposure in HSF. In conclusion, high UVA exposure reduces TGF-ß signaling and collagen I production by modulating Smad levels in HSF. The effects of overexposure to high-intensity UVA on myopia control require further investigations.

Iron Brain Menace: The Involvement of Ferroptosis in Parkinson Disease.

Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD is associated with iron accumulation and is suggested to be driven in part by the novel cell death pathway, ferroptosis. A unique modality of cell death, ferroptosis is mediated by iron-dependent phospholipid peroxidation. The mechanisms of ferroptosis inhibitors enhance antioxidative capacity to counter the oxidative stress from lipid peroxidation, such as through the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis and the coenzyme Q10 (CoQ10)/FSP1 pathway. Another means to reduce ferroptosis is with iron chelators. To date, there is no disease-modifying therapy to cure or slow PD progression, and a recent topic of research seeks to intervene with the development of PD via regulation of ferroptosis. In this review, we provide a discussion of different cell death pathways, the molecular mechanisms of ferroptosis, the role of ferroptosis in blood-brain barrier damage, updates on PD studies in ferroptosis, and the latest progress of pharmacological agents targeting ferroptosis for the intervention of PD in clinical trials.

Outcomes and eye care knowledge in rhegmatogenous retinal detachment patients with a history of laser refractive surgery for myopia.

Purpose: To investigate the surgical outcomes and eye care knowledge of patients with rhegmatogenous retinal detachment (RRD) who had previously undergone laser refractive surgery (LRS) for myopia in a myopia epidemic area. Methods: This retrospective study included patients with primary RRD who underwent surgery and had a history of LRS for myopia at a tertiary medical center. Data were reviewed from medical charts to analyse the surgical outcomes. Questions about eye care knowledge and attitude toward myopia and LRS were obtained. Results: A total of 774 patients underwent RRD surgery, among whom 341 (44%) had myopia > -3 dioptres, 66% of whom had high myopia. Thirty eyes of 26 patients had a history of LRS for myopia. The mean age of patients with a history of LRS was significantly lower than that of those without a history of LRS (45.7 ± 2.9 years vs. 53.8 ± 1.0, p < 0.001). The mean pre-LRS spherical equivalent was -8.66 ± 0.92 (range: -3.00--12.00) dioptres. In more than half the patients (n = 15, 57.7%), the interval between LRS and RRD was more than 10 years. The primary retinal reattachment rate was only 60%, whereas the final retinal reattachment rate was 93%. The mean final visual acuity (VA) improved from a 20/286 to 20/105 (p = 0.006). Linear mixed model analysis showed factors of male sex and macular detachment were significant with poor visual outcome (p = 0.046 and 0.008) Eye care knowledge obtained from the 19 RRD patients with history of LRS, 47% of patients (9/19) mistakenly thought that LRS could cure myopia and its complications, and 63% of patients were less willing to visit an ophthalmologist because uncorrected VA improvement after LRS. Eighty-four percent thought that proper knowledge and more education about LRS and myopia for the public are important. Conclusion: In the RRD patients with a history of LRS for myopia, their age was relative younger. Male sex and macular detachment were associated with poor visual outcome. More education with proper knowledge of LRS, myopia and RRD is recommended for the patients to prevent or early detect the occurrence of RRD.

5-Lipoxygenase Inhibition Protects Retinal Pigment Epithelium from Sodium Iodate-Induced Ferroptosis and Prevents Retinal Degeneration.

Excessive reactive oxygen species (ROS) contribute to damage of retinal cells and the development of retinal diseases including age-related macular degeneration (AMD). ROS result in increased metabolites of lipoxygenases (LOXs), which react with ROS to induce lipid peroxidation and may lead to ferroptosis. In this study, the effect of 5-LOX inhibition on alleviating ROS-induced cell death was evaluated using sodium iodate (NaIO3) in the retinal pigment epithelium (RPE) cell line ARPE-19 and a mouse model investigating oxidative stress in AMD. We demonstrated that NaIO3 induced cell death in the RPE cells through mechanisms including ferroptosis. Inhibition of 5-LOX with specific inhibitor, Zileuton, or siRNA knockdown of ALXO5 mitigated NaIO3-induced lipid peroxidation, mitochondrial damage, DNA impairment, and cell death in ARPE-19 cells. Additionally, in the mouse model, pretreatment with Zileuton reduced the NaIO3-induced lipid peroxidation of RPE cells, cell death in the photoreceptor layer of the retina, inflammatory responses, and degeneration of both the neuroretina and RPE monolayer cells. Our results suggest that 5-LOX plays a crucial role in ROS-induced cell death in the RPE and that regulating 5-LOX activity could be a useful approach to control ROS and ferroptosis-induced damage, which promote degeneration in retinal diseases.

Two Birds One Stone: The Neuroprotective Effect of Antidiabetic Agents on Parkinson Disease-Focus on Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease affecting more than 1% of the population over 65 years old. The etiology of the disease is unknown and there are only symptomatic managements available with no known disease-modifying treatment. Aging, genes, and environmental factors contribute to PD development and key players involved in the pathophysiology of the disease include oxidative stress, mitochondrial dysfunction, autophagic-lysosomal imbalance, and neuroinflammation. Recent epidemiology studies have shown that type-2 diabetes (T2DM) not only increased the risk for PD, but also is associated with PD clinical severity. A higher rate of insulin resistance has been reported in PD patients and is suggested to be a pathologic driver in this disease. Oral diabetic drugs including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to provide neuroprotective effects in both PD patients and experimental models; additionally, antidiabetic drugs have been demonstrated to lower incidence rates of PD in DM patients. Among these, the most recently developed drugs, SGLT2 inhibitors may provide neuroprotective effects through improving mitochondrial function and antioxidative effects. In this article, we will discuss the involvement of mitochondrial-related oxidative stress in the development of PD and potential benefits provided by antidiabetic agents especially focusing on sglt2 inhibitors.

Multiple Single Nucleotide Polymorphism Testing Improves the Prediction of Diabetic Retinopathy Risk with Type 2 Diabetes Mellitus.

Diabetic retinopathy (DR) is one of the most frequent causes of irreversible blindness, thus prevention and early detection of DR is crucial. The purpose of this study is to identify genetic determinants of DR in individuals with type 2 diabetic mellitus (T2DM). A total of 551 T2DM patients (254 with DR, 297 without DR) were included in this cross-sectional research. Thirteen T2DM-related single nucleotide polymorphisms (SNPs) were utilized for constructing genetic risk prediction model. With logistic regression analysis, genetic variations of the FTO (rs8050136) and PSMD6 (rs831571) polymorphisms were independently associated with a higher risk of DR. The area under the curve (AUC) calculated on known nongenetic risk variables was 0.704. Based on the five SNPs with the highest odds ratio (OR), the combined nongenetic and genetic prediction model improved the AUC to 0.722. The discriminative accuracy of our 5-SNP combined risk prediction model increased in patients who had more severe microalbuminuria (AUC = 0.731) or poor glycemic control (AUC = 0.746). In conclusion, we found a novel association for increased risk of DR at two T2DM-associated genetic loci, FTO (rs8050136) and PSMD6 (rs831571). Our predictive risk model presents new insights in DR development, which may assist in enabling timely intervention in reducing blindness in diabetic patients.

Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment.

Currently, no pharmacotherapy has been proven effective in treating photoreceptor degeneration in patients. Discovering readily available and safe neuroprotectants is therefore highly sought after. Here, we investigated nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), in a retinal detachment (RD) induced photoreceptor degeneration. NMN administration after RD resulted in a significant reduction of TUNEL+ photoreceptors, CD11b+ macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content (PCC), and a preservation of the outer nuclear layer (ONL) thickness. NMN administration significantly increased NAD+ levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression. Delayed NMN administration still exerted protective effects after RD. Mechanistic in vitro studies using 661W cells revealed a SIRT1/HO-1 signaling as a downstream effector of NMN-mediated protection under oxidative stress and LPS stimulation. In conclusion, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.

Oxidative stress enhanced the transforming growth factor-ß2-induced epithelial-mesenchymal transition through chemokine ligand 1 on ARPE-19 cell.

Fibroblast-like transformation of retinal pigment epithelial (RPE) cells is a pathological feature of proliferative vitreoretinopathy (PVR) that may cause blindness. The effect of oxidative stress alone or together with transforming growth factor-beta 2 (TGF-ß2) on epithelial-mesenchymal transformation (EMT) is not fully understood in RPE. TGF-ß2 induced the upregulation EMT markers including α-smooth muscle actin (α-SMA), Snail, and Slug and downregulation of E-cadherin (E-cad) in ARPE-19 cells. Hydrogen peroxide (H2O2) not only upregulated α-SMA but also enhanced the effect of TGF-ß2 on the expression of Snail and Slug. The CXCL family of cytokines could be the mediators of EMT induced by H2O2 and TGF-ß2. H2O2 induced CXCL1, that upregulated α-SMA and fibronectin. Both SB225002, an inhibitor of CXCR2, and antioxidant N-acetylcysteine suppressed the TGF-ß2-induced EMT in ARPE-19 cells. Taken together, the results suggest that oxidative stress enhanced TGF-ß2-induced EMT through the possible autocrine effect of CXCL1 on CXCR2 in ARPE-19 cells.

Lysosome-associated membrane protein-2 deficiency increases the risk of reactive oxygen species-induced ferroptosis in retinal pigment epithelial cells.

Lysosome-associated membrane protein-2 (LAMP2), is a highly glycosylated lysosomal membrane protein involved in chaperone mediated autophagy. Mutations of LAMP2 cause the classic triad of myopathy, cardiomyopathy and encephalopathy of Danon disease (DD). Additionally, retinopathy has also been observed in young DD patients, leading to vision loss. Emerging evidence show LAMP2-deficiency to be involved in oxidative stress (ROS) but the mechanism remains obscure. In the present study, we found that tert-butyl hydroperoxide or antimycin A induced more cell death in LAMP2 knockdown (LAMP2-KD) than in control ARPE-19 cells. Mechanistically, LAMP2-KD reduced the concentration of cytosolic cysteine, resulting in low glutathione (GSH), inferior antioxidant capability and mitochondrial lipid peroxidation. ROS induced RPE cell death through ferroptosis. Inhibition of glutathione peroxidase 4 (GPx4) increased lethality in LAMP2-KD cells compared to controls. Cysteine and glutamine supplementation restored GSH and prevented ROS-induced cell death of LAMP2-KD RPE cells.

Genetic LAMP2 deficiency accelerates the age-associated formation of basal laminar deposits in the retina.

The early stages of age-related macular degeneration (AMD) are characterized by the accumulation of basal laminar deposits (BLamDs). The mechanism for BLamDs accumulating between the retinal pigment epithelium (RPE) and its basal lamina remains elusive. Here we examined the role in AMD of lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes/phagosomes. LAMP2 was preferentially expressed by RPE cells, and its expression declined with age. Deletion of the Lamp2 gene in mice resulted in age-dependent autofluorescence abnormalities of the fundus, thickening of Bruch's membrane, and the formation of BLamDs, resembling histopathological changes occurring in AMD. Moreover, LAMP2-deficient mice developed molecular signatures similar to those found in human AMD-namely, the accumulation of APOE, APOA1, clusterin, and vitronectin-adjacent to BLamDs. In contrast, collagen 4, laminin, and fibronectin, which are extracellular matrix proteins constituting RPE basal lamina and Bruch's membrane were reduced in Lamp2 knockout (KO) mice. Mechanistically, retarded phagocytic degradation of photoreceptor outer segments compromised lysosomal degradation and increased exocytosis in LAMP2-deficient RPE cells. The accumulation of BLamDs observed in LAMP2-deficient mice was eventually followed by loss of the RPE and photoreceptors. Finally, we observed loss of LAMP2 expression along with ultramicroscopic features of abnormal phagocytosis and exocytosis in eyes from AMD patients but not from control individuals. Taken together, these results indicate an important role for LAMP2 in RPE function in health and disease, suggesting that LAMP2 reduction may contribute to the formation of BLamDs in AMD.

RIP1 kinase mediates angiogenesis by modulating macrophages in experimental neovascularization.

Inflammation plays an important role in pathological angiogenesis. Receptor-interacting protein 1 (RIP1) is highly expressed in inflammatory cells and is known to play an important role in the regulation of apoptosis, necroptosis, and inflammation; however, a comprehensive description of its role in angiogenesis remains elusive. Here, we show that RIP1 is abundantly expressed in infiltrating macrophages during angiogenesis, and genetic or pharmacological inhibition of RIP1 kinase activity using kinase-inactive RIP1K45A/K45A mice or necrostatin-1 attenuates angiogenesis in laser-induced choroidal neovascularization, Matrigel plug angiogenesis, and alkali injury-induced corneal neovascularization in mice. The inhibitory effect on angiogenesis is mediated by caspase activation through a kinase-independent function of RIP1 and RIP3. Mechanistically, infiltrating macrophages are the key target of RIP1 kinase inhibition to attenuate pathological angiogenesis. Inhibition of RIP1 kinase activity is associated with caspase activation in infiltrating macrophages and decreased expression of proangiogenic M2-like markers but not M1-like markers. Similarly, in vitro, catalytic inhibition of RIP1 down-regulates the expression of M2-like markers in interleukin-4-activated bone marrow-derived macrophages, and this effect is blocked by simultaneous caspase inhibition. Collectively, these results demonstrate a nonnecrotic function of RIP1 kinase activity and suggest that RIP1-mediated modulation of macrophage activation may be a therapeutic target of pathological angiogenesis.

Fixation behavior in macular dystrophy assessed by microperimetry.

PURPOSE: To investigate the fixation behavior in macular dystrophy using microperimetry. METHODS: This retrospective study included patients with macular dystrophy and unilateral macular pucker. Macular dystrophic eyes were compared based on fixation within or outside of the atrophic region. The normal fellow eyes in patients with unilateral macular pucker formed the control group. Clinical and demographic characteristics of age, sex, best-corrected visual acuity, spherical equivalent, and fixation behavior (which included foveal mean sensitivity (MS), fixation MS, MS improvement, stability, centrality, and eccentric distance of fixation) were analyzed. A total of 58 patients were recruited, comprising 29 eyes of 29 patients in the macular dystrophy group and 29 eyes of 29 patients in the control group. RESULTS: Compared to the control group, patients with macular dystrophy had significantly poorer visual acuity, foveal MS, fixation MS, stability, and centrality, and more eccentric preferred retinal locations (PRLs). In macular dystrophy, the PRLs were most common on the superior side (48.3%). Compared to fixation in the atrophic region, PRLs out of the atrophic lesion gained more MS (7.41 vs. 0.89 dB, p = 0.001), although with less stable fixation (10.0 vs. 47.4%, p = 0.044). By multivariate linear regression, eccentric distance was found to be significantly associated with MS improvement (p = 0.023). CONCLUSIONS: The commonest location of PRLs in macular dystrophy is anatomically superior to the lesion. The dystrophic eye can gain better sensitivity by using PRLs outside the atrophic area.

Factors associated with corneal epithelial defects after pars plana vitrectomy.

PURPOSE: To investigate the risk factors associated with corneal epithelial defects (CED) and delayed healing (exceeding 1 week) following pars plana vitrectomy (PPV). METHODS: This retrospective study enrolled patients who underwent PPV at a single center in Taiwan between 2011 and 2012. Medical records were reviewed, including demographic, underlying disease, surgical indication, operation parameters, and existence of CED. These data were statistically analyzed. All patients were evaluated during follow-ups at day 1 and week 1 after PPV. Patients with persistent CED 1 week after PPV were diagnosed with delayed healing. RESULTS: A total of 255 patients were included in the study, consisting of 139 men and 116 women, with a mean age of 56.9 years. PPV was performed under the indications of rhegmatogenous retinal detachment (RRD), diabetic retinopathy, or vitreoretinal interface disease. Out of 255 eyes, 59 developed CED 1 day after surgery (23.1%), and CED was associated with younger age, diabetes mellitus (DM), RRD, longer duration of surgery, and silicon oil use during surgery. Among them, seven patients (11.9%) demonstrated delayed healing, which was associated with a higher rate of DM (p = 0.085), compared to patients who healed within 1 week. CONCLUSION: Patients with RRD, longer duration of surgery, and DM may be at risk of developing CED after PPV. In addition, patients with DM demonstrated a higher incidence of delayed corneal healing.

Retinal Detachment Associated With Basketball-Related Eye Trauma.

PURPOSE: Basketball is a popular sport involving significant body contact, which may frequently result in ocular trauma. The aim of this study was to evaluate the characteristics and visual outcomes of retinal detachment associated with basketball-related injury. DESIGN: Retrospective, interventional case series. METHODS: We reviewed the course of patients who sustained traumatic retinal detachment from basketball-related ocular trauma between 2003 and 2015. RESULTS: Thirteen patients were evaluated for basketball-related traumatic retinal detachment. Twelve (92%) were male and 1 (8%) female, with an average age of 18.2 years. The majority (9 of 13, 70%) of patients had moderate-to-high myopia, and none were using protective eyewear when they sustained the eye trauma. Rhegmatogenous retinal detachment was observed in all eyes. The preoperative mean visual acuity was 20/625 (range, hand motions to 20/20). Initial surgery using scleral buckling alone was performed in most (8 of 13, 62%) of the patients. Retinal reattachment was achieved in 10 (76%) eyes after the first operation and in 12 (92%) at the end of the intervention. The mean follow-up was 3.9 years (range, 4 months to 12 years). The visual acuity during last follow-up was 20/231 (range, light perception to 20/20). In the multivariable analysis, initial visual acuity was an independent factor affecting the final visual outcome (P = .006). CONCLUSION: Retinal detachment associated with basketball-related injury may cause severe visual loss. In the current study, all retinal detachments were of rhegmatogenous type and commonly occurred in young individuals with myopia. Initial visual acuity was associated with the prognosis. Risk awareness for early detection and intervention are important in these traumas.

GORE-TEX VASCULAR GRAFT FOR MACULAR BUCKLING IN HIGH MYOPIA EYES.

PURPOSE: To evaluate a new application of an expanded polytetrafluoroethylene (Gore-Tex) vascular graft for use in macular buckling surgery for treatment of highly myopic eyes. METHODS: The Gore-Tex vascular graft was used as a macular buckling material in eight consecutive cases of myopic macular diseases which included fovea detachment, foveoschisis, or macular hole retinal detachment. RESULTS: Retinal reattachment was achieved in all cases except one which had partial resolution (88%). The postoperative best-corrected visual acuity ranged from 20/2000 to 20/100 depending on the degree preexisting macular degeneration, and significant better than the preoperative best-corrected visual acuity (P = 0.048, paired t-test). During the follow-up period, which ranged from 8 months to 3 years, no eye developed buckle-related complications such as infection or dislocation. CONCLUSION: The initial pilot results from this series using a Gore-Tex graft for macular buckling is promising. Throughout the follow-up period, the Gore-Tex was well tolerated in the highly myopic eyes. Large scale and long-term follow-up is warranted.

Diabetic Retinopathy Is Strongly Predictive of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes.

A well-established, comprehensive, and simple test battery was used here to re-evaluate risk factors for cardiovascular autonomic neuropathy (CAN) in type 2 diabetes. One hundred and seventy-four patients with type 2 diabetes were evaluated through the methods of deep breathing and Valsalva maneuver for correlation with factors that might influence the presence and severity of CAN. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment, and CAN was defined as a CASS score ≥2. Results showed that nephropathy, duration of diabetes, blood pressure, uric acid, and the presence of retinopathy and metabolic syndrome significantly correlated with the CASS score. Age may not be a risk factor for diabetic CAN. However, the effects of diabetes on CAN are more prominent in younger patients than in older ones. Diabetic retinopathy is the most significant risk factor predictive of the presence of CAN in patients with type 2 diabetes.

High-fat diet induces toll-like receptor 4-dependent macrophage/microglial cell activation and retinal impairment.

PURPOSE: The toll-like receptor 4 (TLR4) signaling pathway is involved in chronic inflammation and insulin resistance, which are associated with obesity and diabetes mellitus. In the present study, a model of high-fat diet (HFD) feeding of mice was used to investigate the role of TLR4 in overnutrition- and obesity-associated inflammation and infiltration of macrophages and microglia in the retina. METHODS: Wild-type C57BL/6 and TLR4 knockout (TLR4KO; B6.B10ScN-Tlr4(lps-del)/JthJ) mice were fed a HFD or control chow diet (CD) for 6 months. The TLR4 expression, the relative increase in macrophages/microglia (CD11b(+) and CD45(+) cells), the presence of markers of oxidative stress (gp91phox and malondialdehyde; MDA), and DNA damage (phosphorylated histone H2AX; γH2AX) were assessed by real-time PCR and immunofluorescence studies. RESULTS: The HFD for 6 months showed increased obesity, glucose intolerance, and insulin resistance in mice. Toll-like receptor 4 expression was found in vascular pericytes at the inner retina. Increased CD11b(+) and CD45(+) cells, phosphorylated NF-κB, interleukin-6, gp91phox, MDA, and γH2AX were observed in the retina of mice fed a HFD compared to CD counterparts. TLR4KO mice did not show the adverse effects of HFD. CONCLUSIONS: Our results indicate that HFD-induced macrophage/microglial cell activation and retinal impairment were reduced in the absence of TLR4. The findings suggest that TLR4 is implicated in the pathogenesis of retinal diseases caused by metabolic disorders.