Oxidative stress in retinal pigment epithelium degeneration:from pathogenesis to therapeutic targets in dry age-related macular degeneration

Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration;however, effective treatment is not yet available for geographical atrophy in dry agerelated macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human agerelated macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.

Asymmetric Drying and Wetting Trends in Eastern and Western China

As an important factor that directly affects agricultural production, the social economy, and policy implementation,observed changes in dry/wet conditions have become a matter of widespread concern. However, previous research has mainly focused on the long-term linear changes of dry/wet conditions, while the detection and evolution of the non-linear trends related to dry/wet changes have received less attention. The non-linear trends of the annual aridity index, obtained by the Ensemble Empirical Mode Decomposition(EEMD) method, reveal that changes in dry/wet conditions in China are asymmetric and can be characterized by contrasting features in both time and space in China. Spatially, most areas in western China have experienced transitions from drying to wetting, while opposite changes have occurred in most areas of eastern China. Temporally, the transitions occurred earlier in western China compared to eastern China. Research into the asymmetric spatial characteristics of dry/wet conditions compensates for the inadequacies of previous studies, which focused solely on temporal evolution;at the same time, it remedies the inadequacies of traditional research on linear trends over centennial timescales. Analyzing the non-linear trend also provides for a more comprehensive understanding of the drying/wetting changes in China.

Anthropogenic Influence on Decadal Changes in Concurrent Hot and Dry Events over China around the Mid-1990s

The frequency and duration of observed concurrent hot and dry events(HDEs) over China during the growing season(April–September) exhibit significant decadal changes across the mid-1990s. These changes are characterized by increases in HDE frequency and duration over most of China, with relatively large increases over southeastern China(SEC), northern China(NC), and northeastern China(NEC). The frequency of HDEs averaged over China in the present day(PD,1994–2011) is double that in the early period(EP, 1964–81);the duration of HDEs increases by 60%. Climate experiments with the Met Office Unified Model(MetUM-GOML2) are used to estimate the contributions of anthropogenic forcing to HDE decadal changes over China. Anthropogenic forcing changes can explain 60%–70% of the observed decadal changes,suggesting an important anthropogenic influence on HDE changes over China across the mid-1990s. Single-forcing experiments indicate that the increase in greenhouse gas(GHG) concentrations dominates the simulated decadal changes,increasing the frequency and duration of HDEs throughout China. The change in anthropogenic aerosol(AA) emissions significantly decreases the frequency and duration of HDEs over SEC and NC, but the magnitude of the decrease is much smaller than the increase induced by GHGs. The changes in HDEs in response to anthropogenic forcing are mainly due to the response of climatological mean surface air temperatures. The contributions from changes in variability and changes in climatological mean soil moisture and evapotranspiration are relatively small. The physical processes associated with the response of HDEs to GHG and AA changes are also revealed.

Effect of different drying methods on the amino acids,α-dicarbonyls and volatile compounds of rape bee pollen

The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed vacuum drying(PVD),freeze drying(FD),infrared drying(IRD),hot-air drying(HAD)and sun drying(SD)on free amino acids(FAAs),α-dicarbonyl compounds(α-DCs)and volatile compounds(VOCs)in rape bee pollen(RBP)were determined.The results showed that FD significantly released the essential amino acids(EAAs)compared with fresh samples while SD caused the highest loss.Glucosone was the dominantα-DCs in RBP and the highest loss was observed after PVD.Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances(especially aldehydes)than the other four drying methods.Comprehensively,FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.

Astrocyte syncytium:from neonatal genesis to aging degeneration

Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).

Different concentrations of hyaluronic acid eye drops for dry eye syndrome: a systematic review and Meta-analysis

AIM:To compare high or low concentration of hyaluronic acid eye drops(HY)for dry eye syndromes(DES).METHODS:Randomized controlled trials(RCTs)comparing various concentrations of HY were searched in PubMed,Embase,Web of Science,Cochrane,SinoMed,CNKI,Wanfang Database,CQVIP,and Chinese journals databases between inception and July 2023.Pooled standardized mean differences(SMD)or weighted mean difference(WMD)with 95%confidence intervals(CI)from RCTs evaluating Schirmer’s I test(SIT),corneal fluorescein staining score(CFS),tear breakup time(TBUT),DES score(DESS),and Ocular Surface Disease Index(OSDI)were calculated.Sensitivity analysis,Egger’s test and Meta-regression analysis were performed for all indicators.RESULTS:We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria,involving 1796 cases.High-concentrations group significantly improved the outcome of CFS according to random effects modelling(SMD,-3.37;95%CI,-5.25 to-1.48;P=0.0005).The rest of the results were not statistically significant,including indicators such as SIT,TBUT,DESS and OSDI.CONCLUSION:For dry eyes with positive corneal staining,a high concentration of HY is recommended,whereas in other cases,a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

Wearable multilead ECG sensing systems using on-skin stretchable and breathable dry adhesives

Electrocardiogram(ECG)monitoring is used to diagnose cardiovascular diseases,for which wearable electronics have attracted much attention due to their lightweight,comfort,and long-term use.This study developed a wearablemultilead ECG sensing system with on-skin stretchable and conductive silver(Ag)-coated fiber/silicone(AgCF-S)dry adhesives.Tangential and normal adhesion to pigskin(0.43 and 0.20 N/cm2,respectively)was optimized by the active control of fiber density and mixing ratio,resulting in close contact in the electrode–skin interface.The breathableAgCF-S dry electrodewas nonallergenic after continuous fit for 24 h and can be reused/cleaned(>100 times)without loss of adhesion.The AgCF encapsulated inside silicone elastomers was overlapped to construct a dynamic network under repeated stretching(10%strain)and bending(90°)deformations,enabling small intrinsic impedance(0.3,0.1 Hz)and contact impedance variation(0.7 k)in high-frequency vibration(70 Hz).All hard/soft modules of the multilead ECG system were integrated into lightweight clothing and equipped with wireless transmission for signal visualization.By synchronous acquisition of I–III,aVR,aVL,aVF,and V4 lead data,the multilead ECG sensing system was suitable for various scenarios,such as exercise,rest,and sleep,with extremely high signal-to-noise ratios.

On dry machining of AZ31B magnesium alloy using textured cutting tool inserts

Magnesium alloys have many advantages as lightweight materials for engineering applications,especially in the fields of automotive and aerospace.They undergo extensive cutting or machining while making products out of them.Dry cutting,a sustainable machining method,causes more friction and adhesion at the tool-chip interface.One of the promising solutions to this problem is cutting tool surface texturing,which can reduce tool wear and friction in dry cutting and improve machining performance.This paper aims to investigate the impact of dimple textures(made on the flank face of cutting inserts)on tool wear and chip morphology in the dry machining of AZ31B magnesium alloy.The results show that the cutting speed was the most significant factor affecting tool flank wear,followed by feed rate and cutting depth.The tool wear mechanism was examined using scanning electron microscope(SEM)images and energy dispersive X-ray spectroscopy(EDS)analysis reports,which showed that at low cutting speed,the main wear mechanism was abrasion,while at high speed,it was adhesion.The chips are discontinuous at low cutting speeds,while continuous at high cutting speeds.The dimple textured flank face cutting tools facilitate the dry machining of AZ31B magnesium alloy and contribute to ecological benefits.

Taurine: a promising nutraceutic in the prevention of retinal degeneration

Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.

Temperature dependence of mechanical properties and damage evolution of hot dry rocks under rapid cooling

Understanding the differences in mechanical properties and damage characteristics of granitoid under high temperatures is crucial for exploring deep geothermal resources.This study analyzes the evolution of the acoustic emission(AE)characteristics and mechanical parameters of granodiorite and granite after heating and water cooling by uniaxial compression and variable-angle shear tests under different temperature gradients.We identify their changes in mesostructure and mineral composition with electron probe microanalysis and scanning electron microscopy.Results show that these two hot dry rocks have similar diagenetic minerals and microstructure,but show significantly different mechanical and acoustic characteristics,and even opposing evolution trends in a certain temperature range.At the temperatures ranging from 100℃to 500℃,the compressive and shear mechanical properties of granodiorite switch repeatedly between weakening and strengthening,and those of granite show a continuous weakening trend.At 600℃,both rocks exhibit a deterioration of mechanical properties.The damage mode of granite is characterized by initiating at low stress,exponential evolutionary activity,and intensified energy release.In contrast,granodiorite exhibits the characteristics of initiating at high stress,volatile evolutionary activity,and intermittent energy release,due to its more stable microstructure and fewer thermal defects compared to granite.As the temperature increases,the initiation and propagation of secondary cracks in granodiorite are suppressed to a certain extent,and the seismicity and brittleness are enhanced.The subtle differences in grain size,microscopic heterogeneity,and mineral composition of the two hot dry rocks determine the different acoustic-mechanical characteristics under heating and cooling,and the evolution trends with temperature.These findings are of great significance for the scientific and efficient construction of rock mass engineering by rationally utilizing different rock strata properties.

Dry Breeding and Dry Planting Techniques for Indica Hybrid Rice in Karst Mountain Areas of Gejiu City

Based on the arable land situation in Gejiu City,upland dry planting of indica hybrid rice is being expanded in Karst mountain areas with a rainfall of over 1400 mm and an altitude of 1100-1600 m to develop grain production.This paper gives a specific description of hybrid rice upland dry seedling technology,upland transplanting technology,fertilization technology,field management,weed prevention and control technology,and disease and pest control.

Evaluation of dry eye disease symptomatology and mental health status among patients with different COVID-19 statuses

AIM:To evaluate dry eye disease(DED)symptomatology and mental health status in different COVID-19 patients.METHODS:A cross-sectional observational design was used.Totally 123 eligible adults(46.34%of men,age range,18-59y)with COVID-19 included in the study from August to November,2022.Ocular Surface Disease Index(OSDI),Five-item Dry Eye Questionnaire(DEQ-5),Hospital Anxiety and Depression Scale(HADS),and Pittsburgh Sleep Quality Index(PSQI)were used in this study.RESULTS:OSDI scores were 6.82(1.25,15.91)in asymptomatic carriers,7.35(2.50,18.38)in mild cases,and 16.67(4.43,28.04)in recurrent cases,with 30.00%,35.56%,and 57.89%,respectively evaluated as having DED symptoms(χ2=7.049,P=0.029).DEQ-5 score varied from 2.00(0,6.00)in asymptomatic carriers,3.00(0,8.00)in mild cases,and 8.00(5.00,10.00)in recurrent cases,with 27.50%,33.33%,and 55.26%,respectively assessed as having DED symptoms(χ2=8.532,P=0.014).The prevalence of clinical anxiety(50.00%)and depression(47.37%)symptoms were also significantly higher in patients with recurrent infection(χ2=24.541,P<0.001;χ2=30.871,P<0.001).Recurrent infection was a risk factor for high OSDI scores[odds ratio,2.562;95%confidence interval(CI),1.631-7.979;P=0.033]and DEQ-5 scores(odds ratio,3.353;95%CI,1.038-8.834;P=0.043),whereas having a fixed occupation was a protective factor for OSDI scores(odds ratio,0.088;95%CI,0.022-0.360;P=0.001)and DEQ-5 scores(odds ratio,0.126;95%CI,0.039-0.405;P=0.001).CONCLUSION:Patients with recurrent COVID-19 have more severe symptoms of DED,anxiety,and depression.

Using choroidal thickness to detect myopic macular degeneration

AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral high myopia(≤−6 diopters)were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.SS-OCT was performed to determine the choroidal thickness,and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia(META-PM)Classification.Presence of MMD was defined as META-PM category 2 or above.RESULTS:A total of 568 right eyes were included for analysis.Eyes with MMD(n=106,18.7%)were found to have older age,longer axial lengths(AL),higher myopic spherical equivalents(SE),and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study(ETDRS)grid sector(P<0.001).The area under the receiver operating characteristic(ROC)curves(AUC)for subfoveal choroidal thickness(0.907)was greater than that of the model,including age,AL,and SE at 0.6249,0.8208,and 0.8205,respectively.The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD(AUC of 0.928 and 0.923,respectively).An outer nasal sector choroidal thickness of less than 74μm demonstrated the highest odds of predicting MMD(OR=33.8).CONCLUSION:Choroidal thickness detects the presence of MMD with high agreement,particularly of the inner and outer nasal sectors of the posterior pole,which appears to be a biometric parameter more precise than age,AL,or SE.

Wetting alternating with partial drying during grain filling increases lysine biosynthesis in inferior rice grain

Lysine content is a criterion of the nutritional quality of rice.Understanding the process of lysine biosynthesis in early-flowering superior grain(SG)and late-flowering inferior grain(IG)of rice would advance breeding and cultivation to improve nutritional quality.However,little information is available on differences in lysine anabolism between SG and IG and the underlying mechanism,and whether and how irrigation regimes affect lysine anabolism in these grains.A japonica rice cultivar was grown in the field and two irrigation regimes,continuous flooding(CF)and wetting alternating with partial drying(WAPD),were imposed from heading to the mature stage.Lysine content and activities of key enzymes of lysine biosynthesis,and levels of brassinosteroids(BRs)were lower in the IG than in the SG at the early grainfilling stage but higher at middle and late grain-filling stages.WAPD increased activities of these key enzymes,BR levels,and contents of lysine and total amino acids in IG,but not SG relative to CF.Application of 2,4-epibrassinolide to rice panicles in CF during early grain filling reproduced the effects of WAPD,but neither treatment altered the activities of enzymes responsible for lysine catabolism in either SG or IG.WAPD and elevated BR levels during grain filling increased lysine biosynthesis in IG.Improvement in lysine biosynthesis in rice should focus on IG.

Dry eye rate and its relationship with disease stage in patients with primary hypertension:a cross-sectional study in Vietnam

AIM:To determine the dry eye(DE)rate and its relationship with disease stage in patients with primary hypertension.METHODS:A cross-sectional study included 432 patients with primary hypertension(with an equal number of patients in each group:144 in stage Ⅰ,Ⅱ,and Ⅲ hypertension)and 144 healthy subjects as a control group.The Ocular Surface Disease Index(OSDI)and Schirmer Ⅰ test without anesthetics were conducted on all 576 subjects.Subjects with OSDI scores<13 and Schirmer Ⅰ values equal to or under 10 mm were diagnosed with DE.RESULTS:The ratio of DE in hypertension patients was higher than in the control group(41.7%versus 18.8%;P<0.001).The proportion of patients with DE increased gradually according to the hypertension stage:27.1% in stage Ⅰ,40.3% in stage Ⅱ,and 57.6% in stage Ⅲ,P<0.001.Age,duration of hypertension,plasma urea,creatinine,and high-sensitivity C-reactive protein(CRP-hs)levels in hypertension patients with DE were higher than those without DE,P<0.001.Advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma creatinine,and CRP-hs levels were independent factors associated with DE in primary hypertension patients,P<0.001.CONCLUSION:DE is a common disorder associated with advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma CRP-hs,and creatinine levels in patients with primary hypertension.

Dual‑Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease

Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.

Combined application of organic fertilizer and chemical fertilizer alleviates the kernel position effect in summer maize by promoting post-silking nitrogen uptake and dry matter accumulation

Adjusting agronomic measures to alleviate the kernel position effect in maize is important for ensuring high yields.In order to clarify whether the combined application of organic fertilizer and chemical fertilizer(CAOFCF)can alleviate the kernel position effect of summer maize,field experiments were conducted during the 2019 and 2020 growing seasons,and five treatments were assessed:CF,100%chemical fertilizer;OFCF1,15%organic fertilizer+85%chemical fertilizer;OFCF2,30%organic fertilizer+70%chemical fertilizer;OFCF3,45%organic fertilizer+55%chemical fertilizer;and OFCF4,60%organic fertilizer+40%chemical fertilizer.Compared with the CF treatment,the OFCF1 and OFCF2 treatments significantly alleviated the kernel position effect by increasing the weight ratio of inferior kernels to superior kernels and reducing the weight gap between the superior and inferior kernels.These effects were largely due to the improved filling and starch accumulation of inferior kernels.However,there were no obvious differences in the kernel position effect among plants treated with CF,OFCF3,or OFCF4 in most cases.Leaf area indexes,post-silking photosynthetic rates,and net assimilation rates were higher in plants treated with OFCF1 or OFCF2 than in those treated with CF,reflecting an enhanced photosynthetic capacity and improved postsilking dry matter accumulation(DMA)in the plants treated with OFCF1 or OFCF2.Compared with the CF treatment,the OFCF1 and OFCF2 treatments increased post-silking N uptake by 66.3 and 75.5%,respectively,which was the major factor driving post-silking photosynthetic capacity and DMA.Moreover,the increases in root DMA and zeatin riboside content observed following the OFCF1 and OFCF2 treatments resulted in reduced root senescence,which is associated with an increased post-silking N uptake.Analyses showed that post-silking N uptake,DMA,and grain yield in summer maize were negatively correlated with the kernel position effect.In conclusion,the combined application of 15-30%organic fertilizer and 70-85%chemical fertilizer alleviated the kernel position effect in summer maize by improving post-silking N uptake and DMA.These results provide new insights into how CAOFCF can be used to improve maize productivity.

Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal tract.To investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal tract.We first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal tract.An antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time points.To improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing axons.Using this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after stroke.In addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over time.Meanwhile,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian degeneration.Moreover,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal tract.In conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

RDH12-associated retinal degeneration caused by a homozygous pathogenic variant of 146C>T and literature review

AIM:To describe the clinical,electrophysiological,and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant.METHODS:The patient underwent a complete ophthalmologic examination including best-corrected visual acuity,anterior segment and dilated fundus,visual field,spectral-domain optical coherence tomography(OCT)and electroretinogram(ERG).The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result.Then we reviewed the characteristics of the patients reported with the same variant.RESULTS:A 30-year male presented with severe early retinal degeneration who complained night blindness,decreased visual acuity,vitreous floaters and amaurosis fugax.The best corrected vision was 0.04 OD and 0.12 OS,respectively.The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye.Autofluorescence shows bilateral symmetrical hypo-autofluorescence.ERG revealed that the amplitudes of a-and b-wave were severely decreased.Multifocal ERG showed decreased amplitudes in the local macular area.A homozygous missense variant c.146C>T(chr14:68191267)was found.The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied.CONCLUSION:An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported.The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.