Evaluating the global impact of low physical activity on type 2 diabetes: Insights from the global burden of disease 2019 study.

AIM: We aimed to assess the global implications of low physical activity (LPA) on type 2 diabetes mellitus (T2DM) by utilizing data from the Global Burden of Disease (GBD) 2019. METHODS: The analysis was conducted by examining the age-standardized disability-adjusted life years (DALYs) rates over a 30-year period. To assess the trends, we utilized estimated annual percentage changes (EAPCs). RESULTS: The study revealed a notable increase in the burden of DALYs attributable to T2DM resulting from LPA, with an EAPC of 0.84 (95% confidence interval 0.78-0.89). Among the regions examined, Oceania showed the highest burden, whereas Eastern Europe exhibited the lowest burden. Specifically, within the Central Asia region, a considerable increase in T2DM-LPA DALYs was observed, with an EAPC of 3.18 (95% confidence interval 3.01-3.36). The burden associated with T2DM-LPA DALYs was found to be similar between genders and increased across all age groups, peaking in the 80-84 years. Furthermore, there was a clear association between the socio-demographic index (SDI) and the age-standardized DALYs rate. Regions categorized as low-middle and middle SDI experienced a substantial rise in burden. CONCLUSION: This study highlights a substantial increase in the T2DM-LPA DALYs in low-middle and middle SDI regions, as well as among individuals aged 80-84 years. These findings emphasize the importance of implementing comprehensive global health interventions that promote physical activity, particularly targeting high-risk populations and regions.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. RESULTS: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Superficial Retinal Vessel Density and Foveal Avascular Zone in Myopic Anisometropia: An OCTA-Based Study in Young Chinese Children.

This retrospective study investigated superficial retinal vessel density (SRVLD) and foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) in children with myopic anisometropia. We included 84 eyes of 42 individuals with myopic anisometropia and no posterior segment abnormalities. All eyes underwent OCTA. Individual SRVLD and FAZ area were measured on OCTA. Using a paired t-test, we compared the interocular difference between the fellow eyes for all the measurements. SRVLD was significantly higher in the relatively more myopic eyes than in the fellow eyes in the whole population and in patients with an interocular difference of >1.5 D (p = 003 and 0.01, respectively). In patients with an interocular difference of ≤1.5 D in spherical equivalent refraction, only the nasal sector showed higher SRVLD in the less myopic eyes. SRVLD in the whole image and parafoveal sector was significantly lower in the dominant eye (paired t-test, p = 003 and 0.03, respectively), while other locations showed no difference. The area, perimeter, and circularity index in FAZ parameters showed no difference. SRVLD showed no significant differences between the two types of eyes, with an interocular difference of ≤1.5 D but increased in the relatively more myopic eyes than in the fellow eyes in children with myopic anisometropia, with an interocular difference of >1.5 D. Increasing SRVLD may show a compensatory increase to maintain retinal function and thus maintain normal visual function in the relatively more myopic fellow eyes. As the study to use patients as self-control with OCTA analysis in both eyes, this study provides some reference value for further interpretation of the pathogenesis of anisometropia.

Altered brain network centrality in patients with retinal vein occlusion: a resting-state fMRI study.

AIM: To explore the intrinsic brain activity variations in retinal vein occlusion (RVO) subjects by using the voxel-wise degree centrality (DC) technique. METHODS: Twenty-one subjects with RVO and twenty-one healthy controls (HCs) were enlisted and underwent the resting-state functional magnetic resonance imaging (rs-fMRI) examination. The spontaneous cerebrum activity variations were inspected using the DC technology. The receiver operating characteristic (ROC) curve was implemented to distinguish the DC values of RVOs from HCs. The relationships between DC signal of definite regions of interest and the clinical characteristics in RVO group were evaluated by Pearson's correlation analysis. RESULTS: RVOs showed notably higher DC signals in right superior parietal lobule, middle frontal gyrus and left precuneus, but decreased DC signals in left middle temporal gyrus and bilateral anterior cingulated (BAC) when comparing with HCs. The mean DC value of RVOs in the BAC were negatively correlated with the anxiety and depression scale. CONCLUSION: RVO is associated aberrant intrinsic brain activity patterns in several brain areas including pain-related as well as visual-related regions, which might assist to reveal the latent neural mechanisms.

The Prevalence of Glaucoma and Its Related Factors in Rural Residents: A Cross-Sectional Study in Jiangxi, China.

BACKGROUND: This study aims to investigate the prevalence of glaucoma and its related factors among residents aged 40 and over in Jiangxi Province, China, and provide a scientific basis for the prevention and control of glaucoma. METHODS: The cluster sampling method was used to randomly select six townships. Similarly, eight villages were randomly selected from each sample township. A total of 5385 rural residents from 48 villages were collected for a questionnaire survey. A logistic regression model was used to explore the personal behavioral factors related to glaucoma. RESULTS: Among the 5385 participants, the prevalence rate of glaucoma was 1.4%. The logistic regression model found that alcohol consumption, vegetable consumption, physical exercise, daily reading time, and frequent reading environment were related to glaucoma. CONCLUSION: To prevent the occurrence of glaucoma, it is important for rural residents to reduce the frequency of alcohol consumption, increase the frequency of vegetable consumption and physical exercise, control the length of daily reading, and read in a moderately lit environment.

A comparison of visual acuity measured by ETDRS chart and Standard Logarithmic Visual Acuity chart among outpatients.

AIM: To compare the results of visual acuity (VA) measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart, 5 m Standard Logarithm Visual Acuity (5SL) chart, and 2.5 m Standard Logarithm Visual Acuity (2.5SL) chart in outpatients of age 12-80y. METHODS: Each patient (totally 2000 outpatients) had both eyes tested with ETDRS chart at 4 m, 5SL chart at 5 m, and 2.5SL chart at 2.5 m in random order. The VA values of outpatients were categorized by ages. VA values were expressed by logMAR recording method. RESULTS: The mean VA results of ETDRS charts, 5SL, and 2.5SL chart were 0.52±0.28, 0.50±0.30, and 0.46±0.28 logMAR, respectively. There was a statistically significant difference in the three eye charts in the whole group (P<0.001). For all subjects, the correlation of VA tested with three charts was statistically significant (Spearman correlation coefficient=0.944, 0.937, 0.946, all P<0.001). Bland-Altman analysis shows the 95% limits of agreement between the 5SL and 2.5SL chart were -0.182 to 0.210, -0.139 to 0.251, and -0.151 to 0.235 logMAR, respectively). CONCLUSION: The agreement between the three eye charts is not high. The VA measured by 5SL chart is slightly better than that by ETDRS chart and 5SL chart would be a suitable alternative when ETDRS chart are not available in the clinical situation. The VA measured by 2.5SL chart is about 0.5 line better than VA tested with ETDRS chart, which may overestimate VA.

Orthokeratology and Low-Intensity Laser Therapy for Slowing the Progression of Myopia in Children.

Orthokeratology (OK) is widely used to slow the progression of myopia. Low-level laser therapy (LLLT) provides sufficient low energy to change the cellular function. This research is aimed at verifying the hypothesis that LLLT treatment could control myopia progression and comparing the abilities of OK lenses and LLLT to control the refractive error of myopia. Eighty-one children (81 eyes) who wore OK lenses, 74 children (74 eyes) who underwent LLLT treatment, and 74 children (74 eyes) who wore single-vision distance spectacles for 6 months were included. Changes in axial length (AL) were 0.23 ± 0.06 mm for children wearing spectacles, 0.06 ± 0.15 mm for children wearing OK lens, and -0.06 ± 0.15 mm for children treated with LLLT for 6 months. Changes in subfoveal choroidal thickness (SFChT) observed at the 6-month examination were -16.84 ± 7.85 µm, 14.98 ± 22.50 µm, and 35.30 ± 31.75 µm for the control group, OK group, and LLLT group, respectively. Increases in AL at 1 month and 6 months were significantly associated with age at LLLT treatment. Changes in AL were significantly correlated with the baseline spherical equivalent refraction (SER) and baseline AL in the OK and LLLT groups. Increases in SFChT at 1 month and 6 months were positively associated with age at enrolment for children wearing OK lens. At 6 months, axial elongation had decelerated in OK lens-wearers and LLLT-treated children. Slightly better myopia control was observed with LLLT treatment than with overnight OK lens-wearing. Evaluations of age, SER, and AL can enhance screening for high-risk myopia, improve the myopia prognosis, and help determine suitable control methods yielding the most benefits.

Validation of handheld fundus camera with mydriasis for retinal imaging of diabetic retinopathy screening in China: a prospective comparison study.

OBJECTIVES: To investigate the clinical validity of using a handheld fundus camera to detect diabetic retinopathy (DR) in China. DESIGN AND SETTINGS: Prospective comparison study of the handheld fundus camera with a standard validated instrument in detection of DR in hospital and a community screening clinic in Guangdong Province, China. PARTICIPANTS: Participants aged 18 years and over with diabetes who were able to provide informed consent and agreed to attend the dilated eye examination with handheld tests and a standard desktop camera. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the proportion of those with referable DR (R2 and above) identified by the handheld fundus camera (the index test) compared with the standard camera. Secondary outcome was the comparison of proportion of gradable images obtained from each test. RESULTS: In this study, we examined 304 people (608 eyes) with each of the two cameras under mydriasis. The handheld camera detected 119 eyes (19.5%) with some level of DR, 81 (13.3%) of them were referable, while the standard camera detected 132 eyes (21.7%) with some level of DR and 83 (13.7%) were referable. It seems that the standard camera found more eyes with referable DR, although McNemar's test detected no significant difference between the two cameras.Of the 608 eyes with images obtained by desktop camera, 598 (98.4%) images were of sufficient quality for grading, 12 (1.9%) images were not gradable. By the handheld camera, 590 (97.0%) were gradable and 20 (3.2%) images were not gradable.The two cameras reached high agreement on diagnosis of retinopathy and maculopathy at all the levels of retinopathy. CONCLUSION: Although it could not take the place of standard desktop camera on clinic fundus examination, the handheld fundus camera showed promising role on preliminary DR screening at primary level in China. To ensure quality images, mydriasis is required.

Acetylcholinesterase inhibition ameliorates retinal neovascularization and glial activation in oxygen-induced retinopathy.

AIM: To investigate whether inhibition of acetylcholinesterase (AChE) by donepezil ameliorate aberrant retinal neovascularization (RNV) and abnormal glial activation in oxygen-induced retinopathy (OIR). METHODS: A mouse model of RNV was induced in postnatal day 7 (P7) mice by exposure to 75% oxygen. Donepezil was administrated to P12 mice by intraperitoneal injection. Expression and localization of AChE in mouse retinas were determined by immunofluorescence. RNV was evaluated by paraffin sectioning and hematoxylin and eosin (HE) staining. Activation of retinal Müller glial cells were examined by immunoblot of glial fibrillary acidic protein (GFAP). rMC-1, a retinal Müller cell line, was used for in vitro study. Expression of hypoxia-induced factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) were determined by Western-blot analysis, enzyme-linked immunosorbent assay (ELISA) or immunostaining. RESULTS: Aberrant RNV and glial activation was observed after OIR. Of note, retinal AChE was mainly expressed by retinal Müller glial cells and markedly increased in OIR mice. Systemic administration of donepezil significantly reduced RNV and abnormal glial activation in mice with OIR. Moreover, ischemia-induced HIF-1α accumulation and VEGF upregulation in OIR mouse retinas and cultured rMC-1 were significantly inhibited by donepezil intervention. CONCLUSION: AchE is implicated in RNV with OIR. Inhibition of AChE by donepeizl is likely to be a potential therapeutic approach for retinal neovascular diseases.

Inhibition of acetylcholinesterase attenuated retinal inflammation via suppressing NF-κB activation.

Elevated inflammatory cytokines contribute to the pathogenesis of various retinal diseases such as diabetic retinopathy, retinal vasculitis and retinitis. However, the underlying mechanism of retinal inflammation remains largely unknown. Recent studies demonstrated that acetylcholinesterase (ACHE) is an inflammatory indicator in central neural system. This study was aimed to dissect the role of ACHE in retinal inflammation, and its mechanism of action. Retinal inflammation was induced by intravitreal injection of tumor necrosis factor-α (TNF-α) in heterozygous ACHE knockdown mice (ACHE+/-) and wild type mice (ACHE+/+). Donepezil, a well-known ACHE inhibitor, was administrated by daily gavage. Expression of ACHE and intercellular adherent molecule-1 (ICAM-1), infiltration of CD11b+ inflammatory cells, retinal leukostasis and vascular leakage was determined in both ACHE+/- and ACHE+/+ mice. ARPE-19 cells, a human retinal pigment epithelial cell line, were cultured for in vitro assay. Knockdown of ACHE was achieved by lipofectamine-mediated siRNA transfection and pharmaceutical suppression of ACHE was manipulated by donepezil. Cellular expression and distribution of ACHE, ICAM-1, and phosphorylation of NF-κB, IκB and IKKα/ß were detected by western-blot analysis or immunocytochemistry. Retinal expression of ACHE was dramatically upregulated, in parallel with increased ICAM-1 expression, enhanced leukostasis and augmented CD11b+ inflammatory cell infiltration as well as vascular hyperpermeability in ACHE+/+ mice injected with TNF-α. However, TNF-α-injected ACHE+/- mice showed lower level of ICAM-1, less leukostasis and fewer infiltrated CD11b+ cells. Moreover, TNF-α-induced retinal vascular leakage was significantly reduced in ACHE+/- mice. Similarly, TNF-α-induced retinal inflammatory response were also attenuated by donepezil intervention. In addition, TNF-α treatment resulted in significant induction of ACHE, upregulation of ICAM-1 and nuclear translocation of NF-κB, phosphorylation of IκB and IKKα/ß in ARPE-19 cells. However, inhibition of ACHE reduced TNF-α-induced phosphorylation of NF-κB, IκB and IKKα/ß in ARPE-19 cells. The present study reveals a pivotal role of ACHE in retinal inflammation. Inhibition of ACHE attenuates retinal inflammation and retinal leakage likely through suppressing NF-κB signaling activation.

Prevalence and service assessment of cataract in Tibetan areas of Sichuan Province, China: population-based study.

OBJECTIVES: To assess the prevalence of visual impairment (VI) and blindness (BL) due to cataract and cataract surgical outcomes in remote dispersed and high-altitude Tibetan areas of China. DESIGN AND SETTING: A cross-sectional study was conducted among people aged 50 and above in Tibetan Autonomous Prefecture of Kandze (TAPK), China, in 2017. The Rapid Assessment of Avoidable Blindness protocol was followed. PARTICIPANTS: Of 5000 eligible participants, 4764 were examined (response rate 95.3%). PRIMARY AND SECONDARY OUTCOME MEASURES: Cataract VI was defined as lens opacity at visual acuity (VA) levels of <3/60 (Blindness (BL)), ≥3/60 and <6/60 (severe visual impairment (SVI)), ≥6/60 and <6/18 (moderate visual impairment (MVI)), ≥6/18 and <6/12 (early visual impairment (EVI)). RESULTS: The estimated prevalence of cataract BL was 0.61% (95% CI 0.42 to 0.87). With best corrected VA, the estimated prevalence of SVI from cataract was 0.86% (95% CI 0.63 to 1.17); MVI was 2.39% (95% CI 2.00 to 2.87) and EVI was 5.21% (95% CI 4.61 to 5.87). Women in TAPK had a significantly higher prevalence of cataract BL (0.82%, 95% CI 0.54 to 2.15) than men (0.34%, 95% CI 0.16 to 0.70). Women had lower cataract surgical coverage (CSC) by eyes (60.8%, 95% CI 55.5 to 65.8) compared with men (70.1%; 95% CI 63.7 to 75.7). The prevalence of cataract BL was higher among Tibetan (2.28%; 95% CI 1.98 to 2.62) than Han Chinese (1.01%%; 95% CI 0.54% to 1.87%). Overall CSC by person with BL (by better eye) was 82.0% (95% CI 75.2 to 87.6). Among cataract-operated participants, 71.2% had VA equal to or better than 6/18. CONCLUSIONS: The study detected a low prevalence of VI and BL due to cataract with high CSC in the study area compared with many other places in China. Further actions should be taken to improve cataract surgical outcome.

Prevalence and causes of childhood blindness in Huidong County, South China, primary ascertained by the key informants.

PURPOSE: The aim of this study is to ascertain the prevalence and causes of childhood blindness and severe visual impairment (BL/SVI) in Huidong, South China. METHODS: This cross-sectional study was conducted in early 2017 in areas of 139 816 children at the age of 0-15 as the study subjects. We used the trained key informants (KIs) to do preliminary visual test in the communities and refer those children suspected with blindness or unable to count fingers with both eyes at 5 m to hospital for further examination by paediatric ophthalmologist for causes. The WHO's definition of BL/SVI was used, as blindness is best-corrected visual acuity worse than 0.05 in better eye and SVI is equal to or better than 0.05 but worse than 0.1 in better eye. RESULTS: Three hundred and fourteen KIs were trained. In total, 42 children with BL/SVI were found, and among them over half (22, 52.4%) were due to posterior segment disorders by anatomic site and 18 (42.9%) children were potentially preventable; these included BL/SVI caused by factors at children's development in intrauterine and after birth. This established the prevalence of BL/SVI was at 0.31/1000 (95% CI 0.28 to 0.34/1000). CONCLUSION: A low prevalence of childhood blindness was documented in this study. Establishment of surveillance system for disabled children including those with BL/SVI and better health education on eye care to the public according to the surveillance outcomes would help to reduce avoidable children's BL/SVI further in China.

Salutary effect of fenofibrate on type 1 diabetic retinopathy via inhibiting oxidative stress-mediated Wnt/ß-catenin pathway activation.

Fenofibrate has been shown to have therapeutic effects on diabetic retinopathy (DR). Our previous studies demonstrated that the oxidative stress-activated Wnt/ß-catenin pathway plays a pathogenic role in diabetic complications. In the present study, we evaluate the effect and mechanism of fenofibrate on regulating the oxidative stress-activated Wnt/ß-catenin pathway by using the genetic type 1 diabetes model of C57BL/6J-Ins2Akita mice and high glucose (HG)-treated ARPE-19. Our results demonstrated that retinal phosphorylation of LRP6 and nuclear ß-catenin were increased in C57BL/6J-Ins2Akita mice suggesting activation of Wnt/ß-catenin signaling. Meanwhile, C57BL/6J-Ins2Akita showed upregulation of oxidant enzyme Nox4 and Nox2 and downregulation of antioxidant enzyme SOD1 and SOD2. All these alterations were reversed in C57BL/6J-Ins2Akita mice with fenofibrate treatment. Moreover, fenofibrate significantly ameliorated diabetes-induced retinal vascular leakage in C57BL/6J-Ins2Akita mice. In cultured ARPE-19, fenofibrate decreased HG-induced Nox2 and Nox4 upregulation, attenuated SOD1 and SOD2 downregulation and inhibited LRP6 phosphorylation. Moreover, activation of Wnt/ß-catenin by Wnt3a conditional medium (WCM) reduced SOD1 and SOD2 and did not affect Nox2 and Nox4. Fenofibrate suppressed WCM-induced LRP6 phosphorylation and reversed SOD downregulation. Importantly, Nox4 overexpression directly phosphorylated LPR6 in ARPE19; conversely, Nox4 knockdown suppressed HG-induced LPR6 phosphorylation. Taken together, Nox-mediated oxidative stress contributes to Wnt/ß-catenin activation in DR. Fenofibrate ameliorated DR through coordinate attenuation of oxidative stress and blockade of Wnt/ß-catenin signaling.

Causes of Visual Impairment and Blindness in the 2006 and 2014 Nine-Province Surveys in Rural China.

PURPOSE: To investigate the primary causes of visual impairment and blindness in rural China. DESIGN: Population-based, cross-sectional study. METHODS: Geographic cluster sampling was used in randomly selecting residents from a rural county/district within 9 provinces in the East Coast, Inland Middle, and West regions of mainland China. Persons aged 50 years or older were enumerated through household visits and invited to examination sites for visual acuity testing and ocular examination. Causes of vision impairment and blindness in 2014 were compared with data from an earlier 2006 survey. RESULTS: Mild visual impairment (20.4% prevalence) was caused by uncorrected refractive error in two thirds of cases and by cataract in nearly another one fourth; moderate-to-severe visual impairment (10.3% prevalence) was caused by cataract in over onec half of cases and by uncorrected refractive error in another one fifth; blindness (1.66% prevalence) was caused by cataract in approximately one half of cases and in another one fourth by retinal disease. Primary causes of visual impairment and blindness in cataract-operated eyes were uncorrected refractive error, posterior capsule opacity, and retinal disease. From 2006 to 2014, the proportion of visual impairment caused by uncorrected refractive error increased, but rates for unoperated cataract were reduced. CONCLUSIONS: Uncorrected refractive error and unoperated cataract are the 2 primary causes of mild, moderate, and severe visual impairment in rural China, with unoperated cataract and retinal diseases primary causes for blindness. An effective public health strategy to increase service delivery for these causes would lead to substantial reduction in vision impairment and blindness.

Cataract Surgical Coverage and Visual Acuity Outcomes in Rural China in 2014 and Comparisons With the 2006 China Nine-Province Survey.

PURPOSE: To estimate surgical coverage of cataract-related vision impairment and blindness and visual acuity outcomes in operated eyes in rural China in 2014 with comparisons with the 2006 Nine-Province Survey. DESIGN: Population-based, cross-sectional study. METHODS: Geographical cluster sampling was used in randomly selecting residents from a rural county or semi-rural district within 9 provinces: Beijing, Jiangsu, Guangdong, Heilongjiang, Jiangxi, Hebei, Ningxia, Chongqing, and Yunnan. Persons 50 years of age or older were enumerated through household visits and invited to examination sites for visual acuity testing and ocular examination. Surgical coverage and visual acuity outcomes in 2014 were compared with data from the 2006 survey. RESULTS: Among 51 310 examined persons, surgical coverage among those presenting with cataract-related severe visual impairment or blindness (<20/200) was 62.7% overall, ranging from 43.4% to 83.6% across the 9 study sites. Unoperated cataract was significantly associated with older age, female sex, and lack of education. Presenting visual acuity outcomes ≥ 20/63 in cataract-operated eyes was 62.2% overall, ranging from 51.6% to 78.6%, and 75.2%, ranging from 67.1% to 81.5%, with best-corrected visual acuity. As a proportional percentage of cataract surgical coverage in 2006, overall surgical coverage increased by 81.4% during the 2006-2014 interval, and by 110% when adjusted for visual acuity outcomes ≥ 20/63. CONCLUSIONS: Cataract blindness control is well underway in rural China, as evidenced by significant increases in cataract surgical coverage and improvement in visual acuity outcomes during the 2006-2014 interval. Further efforts are needed to provide greater access to affordable cataract surgery for the elderly, female persons, and those with little or no education.

The prevalence and risk factors of visual impairment among rural residents aged 50 years and above in Yugan county, China.

PURPOSE: The purpose of the study is to assess the prevalence of visual impairment (PVI) among rural residents aged 50 years and above in Yugan county, China. Researchers analyzed risk factors and obtained scientific baseline information for blindness prevention and control. METHODS: Stratified cluster random sampling was used in randomly selecting 5540 rural residents aged ≥50 in Yugan county. Eligible residents were invited to receive visual acuity measurement via ophthalmic examinations. Multivariable logistic regression was performed to analyze any risk factors. RESULTS: A total of 5119 rural residents participated the ophthalmic examination and investigation. The PVI was 19.2%. The prevalence of moderate and severe visual impairment (≥20/400 and <20/60) was 16.9%, and blindness (<20/400) was 2.27%. Multivariable logistic regression showed that age, gender, education, occupation, marital status, drinking attitude, dietary habits, amount of sleep, and daily fruit intake were the main factors that were most predictive of the PVI. CONCLUSION: The PVI among rural residents aged 50 years and above in Yugan county was higher than many other districts. Preventive work in Yuan and other local regions should be focused on older, separated/divorced, or widowed individuals, and those with a lower level of education. Strengthening public awareness consists of educating the public about visual health promotion and blindness intervention, including healthy diet and healthy habits, which will help to reduce visual impairment of the population.

Photoreceptor Protection by Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF).

Retinal degenerations are a major cause of vision impairment and blindness. Neuroprotective therapy is a promising therapeutic strategy for retinal degenerative diseases. We investigated a novel neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) in the retina. MANF is expressed at a high level during postnatal development and the expression declines to a lower level as the retina matures. Müller cells are the major cells expressing MANF. It is also found in the retinal ganglion cells, in the inner nuclear layer (INL) neurons, and in retinal pigment epithelial (RPE) cells. Intravitreal injection of recombinant human (rh)MANF significantly protected rod and cone photoreceptors in rats carrying the rhodopsin S334ter mutation, and preserved electroretinograms (ERGs) in the rd10 (Pde6brd10/rd10 ) mice. These results indicate that MANF is a native protein in the retina and is a potent neurotrophic factor for photoreceptor protection.

The role of Cdk5-mediated Drp1 phosphorylation in Aß1-42 induced mitochondrial fission and neuronal apoptosis.

Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aß) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579. Aß1-42 stimulation increased the phosphorylation level of Drp1 at Serine 579 in mouse cortical neurons. Cdk5 inhibitor roscovitine and knockdown of Cdk5 by a lentiviral vector expressing shRNA targeting Cdk5 (Lenti-Cdk5-shRNA) efficiently prevented Aß1-42 induced Drp1 phosphorylation in neurons. In addition, Aß1-42 stimulation induced markedly mitochondrial fission in neurons. Roscovitine, Lenti-Cdk5-shRNA and expression of phospho-defect mutatant GFP-Drp1-S579A in neurons attenuated Aß1-42 induced mitochondrial fission, whereas expression of phospho-mimetic mutant GFP-Drp1-S579D alone resulted in mitochondiral fission similar to Aß1-42 stimulation. Moreover, Roscovitine and Lenti-Cdk5-shRNA suppressed the cleavage of caspase-3 and protected neurons against Aß1-42 induced neuronal apoptosis.Thus, our data indicate that Drp1 is a direct target of Cdk5, and Cdk5-mediated phosphorylation of Drp1 at Serine 579 regulates Aß1-42 induced mitochondrial fission and neuronal toxicity.

Fenofibrate ameliorates diabetic retinopathy by modulating Nrf2 signaling and NLRP3 inflammasome activation.

Oxidative stress and neuroinflammation contribute significantly to the development and progression of diabetic retinopathy. Fenofibrate has received great attention as it benefits diabetic patients by reducing retinal laser requirement. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a master regulator of anti-oxidative defense. Activation of nucleotide binding domain, leucine-rich repeat-containing receptor (NLR), pyrin domain-containing 3 (NLRP3) inflammasome plays a pivotal role in neuroinflammation. The purpose of this study is to determine whether fenofibrate protects retinas from oxidative damage and neuroinflammation via modulating the Nrf2 pathway and blocking NLRP3 inflammasome activation during diabetes. Diabetes is induced by intraperitoneal injection of streptozotocin in mice. Fenofibrate was given to mice in rodent chow. Upregulation of Nrf2 and NLRP3 inflammasome, enhanced ROS formation, and increased leukostasis and vascular leakage were observed in diabetic mouse retinas. Notably, Nrf2 and Caspase-1 were mainly colocalized with glutamine synthetase, one of the Mȕller cell markers. Fenofibrate further increased the expression of Nrf2 and its target gene NQO-1 and HO-1 and reduced ROS formation in diabetic retinas. In addition, retinal expression of NLRP3, Caspase-1 p20, IL-1ß p17, and ICAM-1 were dramatically increased in vehicle-treated diabetic mice, which were abolished by fenofibrate intervention. Moreover, fenofibrate treatment also attenuated diabetes-induced retinal leukostasis and vascular leakage in mice. Taken together, fenofibrate attenuates oxidative stress and neuroinflammation in diabetic retinas, which is at least partially through modulating Nrf2 expression and NLRP3 inflammasome activation.