Automated Classification of Inherited Retinal Diseases in Optical Coherence Tomography Images Using Few-shot Learning / 生物医学与环境科学（英文）

OBJECTIVE@#To develop a few-shot learning (FSL) approach for classifying optical coherence tomography (OCT) images in patients with inherited retinal disorders (IRDs).@*METHODS@#In this study, an FSL model based on a student-teacher learning framework was designed to classify images. 2,317 images from 189 participants were included. Of these, 1,126 images revealed IRDs, 533 were normal samples, and 658 were control samples.@*RESULTS@#The FSL model achieved a total accuracy of 0.974-0.983, total sensitivity of 0.934-0.957, total specificity of 0.984-0.990, and total F1 score of 0.935-0.957, which were superior to the total accuracy of the baseline model of 0.943-0.954, total sensitivity of 0.866-0.886, total specificity of 0.962-0.971, and total F1 score of 0.859-0.885. The performance of most subclassifications also exhibited advantages. Moreover, the FSL model had a higher area under curves (AUC) of the receiver operating characteristic (ROC) curves in most subclassifications.@*CONCLUSION@#This study demonstrates the effective use of the FSL model for the classification of OCT images from patients with IRDs, normal, and control participants with a smaller volume of data. The general principle and similar network architectures can also be applied to other retinal diseases with a low prevalence.

Peripheral retinopathy under intraoperative optical coherence tomography / 中华眼底病杂志

Objective:To observe the histopathological changes in peripheral retinal lesions under intraoperative optical coherence tomography (iOCT).Methods:A retrospective case series study. Eighty-eight patients (194 eyes) who underwent vitreoretinal surgery in the Department of Ophthalmology at the East Ward of the First Affiliated Hospital of Zhengzhou University from October 2021 to May 2022 in 94 eyes were included in the study. Among them, 49 cases were male and 39 cases were female, with the mean age of (50.93±17.55) years. Ninety-four eyes included 32 eyes with retinal detachment, 6 eyes with proliferative diabetic retinopathy, 28 eyes with vitreous hemorrhage, 8 eyes with ocular trauma, 14 eyes with the macular lesion, 1 eye with uveitis, 1 eye with family exudative vitreoretinopathy (FEVR), 1 eye with acute retinal necrosis (ARN), and 3 eyes with lens dislocation. All affected eyes were examined with iOCT during vitreoretinal surgery. The iOCT scanning of the peripheral retina was performed with the help of episcleral pressure. The pre-equatorial and serrated edge anterior and posterior of retinas were scanned according to the characteristics of different fundus diseases. Various abnormal fundus manifestations were recorded.Results:In 94 eyes, 53 eyes (56.38%, 53/94) have different types of retinopathy in the peripheral retina. Of these, 7 eyes (7.45%) have retinal cystoid degeneration; 19 eyes (20.21%) have lattice degeneration; and 8 eyes (8.51%) have pigment degeneration; 9 eyes (9.57%) have pavement-like degeneration; 7 eyes (7.45%) have small occult holes; 1 eye (1.06%) has familial exudative vitreoretinopathy (FEVR) serrated edge "dyke-like" proliferative degeneration; 4 eyes (4.26%) have vitreous and retinopathy adhesions; and one eye (1.06%) has ARN.Conclusion:With clear refractive media, iOCT can provide clear scans of different peripheral retinal lesions.

Advances in single-cell RNA sequencing in the retina / 中华眼底病杂志

Retina is composed of a heterogeneous population of cell types, each with a unique biological function. Even if the same type of cells, due to genetic heterogeneity will lead to cell function differences. In the past, traditional molecular biological methods cannot resolve variations in their functional roles that arise from these differences, and some cells are difficult to define due to the lack of specific molecular markers or the scarcity of numbers, which hindered the understanding and research of these cells. With the development of biotechnology, single-cell RNA sequencing can analyze and resolve differences in single-cell transcriptome expression profiles, characterize intracellular population heterogeneity, identify new and rare cell subtypes, and more definitely define the characteristics of each cell type. It clarifies the origin, function, and variations in cell phenotypes. Other attributes include pinpointing both disease-related characteristics of cell subtypes and specific differential gene expression patterns, to deepen our understanding of the causes and progression of diseases, as well as to aid clinical diagnosis and targeted therapy.

Research progress on wide-field multimodal image of peripheral retinal degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Peripheral retinal degeneration is a typical lesion in ophthalmic clinical practice. Each type of degeneration affects distinct retinal layers and may lead to sight-threatening complications. Due to its specific location, where current ophthalmic imaging technologies have difficulties observing, the pathogenesis remains unclear despite previous works. This review outlines the characteristics of peripheral retinal degeneration by different wide-field imaging technologies, including ultra-wide field fundus imaging, wide field spectral domain optical coherence tomography, optical coherence tomography angiography and fundus fluorescein angiography, as well as new perspectives on their pathogenesis or pathological characteristics so as to provide new ideas for clinical diagnosis and management. Due to the small size of sample and the lack of prospective and long-term observation of multimodal imaging, it is still impossible to comprehensively evaluate the progression and risk of different types of degeneration. Therefore, it is expected that wide-field multimodal imaging technology will be more widely applied to study the mechanism of peripheral retinal degeneration and guide the clinical practice options.

Recommendations for management of peripheral retinal degenerations

Some degenerations involving the peripheral retina can result in a rhegmatogenous retinal detachment. Currently, there are no clear guidelines for retinal screening and/or management of these peripheral retinal degenerations in patients with or without recent onset posterior vitreous detachment or in those prior to refractive surgery or intraocular procedures. This article aims to provide a set of recommendations for the screening and management of peripheral retinal degenerations based on a common consensus obtained from an expert panel of retinal specialists.

Epigenetic regulation and retinal degenerative diseases / 中华实验眼科杂志

Epigenetics pertains to heritable alterations in gene expression when the nucleotide sequence remains unchanged.Epigenetic regulation mechanisms are diverse, among which DNA methylation, histone modification and non-coding RNA (ncRNA) regulation have been studied in depth.Epigenetic regulation is associated with a variety of human diseases.In the occurrence and development of retinal degenerative diseases, many epigenetic regulation processes such as DNA methylation, histone acetylation and ncRNA regulation have changed.DNA methylation is one of the important regulation processes in retinal degeneration.Aberrant DNA methylation patterns are associated with retinitis pigmentosa (RP), age-related macular degeneration (AMD), inflammation and oxidative stress.Histone acetylation is associated with RP, diabetic retinopathy (DR), glaucoma and retinal nerve ischemic injury.NcRNA is associated with RP, AMD, pathological angiogenesis, and DR.In this article, the application of epigenetic regulation in retinal degeneration was reviewed.

Non-viral vector for gene therapy in inherited retinal degeneration / 中华实验眼科杂志

Inherited retinal degeneration (IRD), a group of diseases often causing irreversible blindness, with multiple pathogenesis, still lacks effective treatments currently.Development of effective therapeutics is a primary research goal.Despite rapid advances in gene therapy during the past decades, the most challenging aspect of gene therapy in clinical applications for IRD is to deliver the curative molecules to achieve optimal expression levels in target cells safely.Apart from high gene transfection efficiency, there are still many limitations, such as immunogenicity, biosafety issue, etc.in the application of viral vectors, which drive the development of gene therapy based on non-viral vectors.As one of the hot research topics in non-viral vectors, encouraging progress has been made in DNA nanoparticles for IRD treatment.The polymer/DNA complex nanoparticle is compacted and encapsulated DNA via peptides, lipids, or polysaccharides.Besides, the non-viral delivery system shows cost, preparation, packaging capacity, and safety advantages, providing a promising non-viral platform for safe and effective treatment of IRD, such as retinitis pigmentosa, Stargardt disease, X-linked juvenile retinoschisis, Leber congenital amaurosis, and so on.In this article, advances in transfection efficiency, targeting ability and safety of non-viral gene therapy and its application in IRD were reviewed.

Effect of 455-470nm array blue light on retinal tissue structure in SD rats / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To observe the changes of retinal and choroid tissue structure in SD rats exposed to blue light from 455nm-470nm array, and to analyze the relationship between irradiation time and tissue structure changes. <p>METHODS: Totally 24 healthy SD male rats of 6wk were selected and randomly divided into normal control group(<i>n</i>=6)and experimental group(<i>n</i>=18). The normal control group was fed for 6wk without any intervention. The experimental group was divided into three groups, which were exposed to the array blue light emitting apparatus(455nm-470nm, 391Lx)for 3, 6 and 12h each day for 6wk.<p>RESULTS: The fundus tissue structure was intact and the cell morphology was normal in the control group. With the extension of blue light irradiation time, the choroid fiber connective tissue of rats in all experimental groups presented hyaline changes, local loose edema, proliferation of small blood vessels, thinning of pigment layer, thinning of cells, gradual reduction of the number of visual cells, and local disappearance. At 3h, the nucleus staining of the experimental group was clear, and no definite changes were observed in the bipolar cell layer and ganglion cell layer. In the 6h and 12h groups, nucleus pyknosis was observed, bipolar cell layer was mildly proliferated, and local cytoplasm was formed in the ganglion cell layer.<p>CONCLUSION: The photoreceptor cells of retina become thinner, atrophy and disappear with the extension of blue light irradiation time. There was no significant relationship between the injury of pigment epithelial cells and the prolonged exposure time of blue light.

Investigation on peripheral retinal degeneration in civil aviation pilots recruitment / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the prevalence on peripheral retinal degeneration and to provide theoretical support for the medical examination of civil aviation pilots recruitment. <p>METHODS: Two thousand four hundred and fifty prospective flight students(Four thousand nine hundred eyes)who received medical examination in Civil Aviation General Hospital from February 2018 to May 2019 were divided into three groups according to diopter after fully mydriatic with tropicamide phenylephrine eye drops(Group A: +3.00 to <-0.50D, Group B: -0.50 to <-3.00D, Group C: -3.00 to -4.50D). The prevalence of peripheral retinal degeneration in each eye was examined, and the results were statistically analyzed. <p>RESULTS:There were five hundred and seventy five students with different types of peripheral retinal degeneration in 2 450 checked students, the prevalence was 23.5%. There was statistical difference in the prevalence of peripheral retinal degeneration in different diopter groups(χ2=65.386, <i>P</i><0.01). There was statistical difference in the prevalence of different types of peripheral retinal degeneration(χ2=351.276, <i>P</i><0.01). There was statistical difference in the prevalence of peripheral retinal degeneration in different parts(χ2=563.712, <i>P</i><0.01). <p>CONCLUSION: Peripheral retinal degeneration is not rare in civil aviation recruitment. The prevalence increases with the progression of myopia, and the lesions are mostly in bitamporal quadrant. It is suggested to identify according to different types.

Coastline like peripheral chorioretinal degeneration as a suspected cause of nasal retinal dialysis

Retinal dialysis is mostly associated with blunt trauma or at times spontaneous. A patient presented to us with fresh rhegmatogenous retinal detachment with no telltale history or signs of trauma. The causative break was retinal dialysis noted on the superonasal periphery. A characteristic peripheral chorioretinal degeneration simulating a coastline almost extending six clock hours was seen in both the eyes. We have discussed this rare presentation and the possibilities of the association between this newly identified lesion and spontaneous retinal dialysis in the following case report.

Intravitreal neurodegenerative and inflammatory mediators in proliferative diabetic retinopathy / Mediadores intravítreos da neurodegeneração e inflamação na retinopatia diabética proliferativa

ABSTRACT Purpose: To compare the intravitreal concentrations of cellular mediators involved in neurodegeneration, inflammation, and angiogenesis in patients with proliferative diabetic retinopathy and other vitreoretinal diseases. Methods: A multiplex bead immunoassay was used to measure vitreous levels of pigment epithelium-derived factor, serum amyloid P, C-reactive protein, complement C4, alpha-1 antitrypsin, vascular endothelial growth factor, platelet-derived growth factor-AA, platelet-derived growth factor-BB, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor alpha and beta in patients undergoing 23-gauge vitrectomy for proliferative diabetic retinopathy and other diagnoses (control group). Results: We evaluated 55 patients, of whom 24 had proliferative diabetic retinopathy and 31 had other diagnoses including vitreous hemorrhage, retinal detachment, macular hole, and epiretinal membrane. Patients with proliferative diabetic retinopathy demonstrated increased levels of serum amyloid P (85.49 vs. 31.38 ng/mL); C-reactive protein (59.89 vs. 41.75 ng/mL), vascular endothelial growth factor (2,330.11 vs. 554.25 pg/mL; p<0.001), platelet-derived growth factor A (127.32 vs. 39.11 pg/mL), platelet-derived growth factor B (29.37 vs. 7.12 pg/mL), interleukin-6 (69.37 vs. 33.58 pg/mL), interleukin-8 (175.25 vs. 59.71 pg/mL), and interleukin-10 (3.70 vs. 1.88 pg/mL); all p<0.004 when compared with the control group. Levels of pigment epithelium-derived factor (30.06 vs. 27.48 ng/mL; p=0.295), complement C4 (570.78 vs. 366.24 ng/mL; p=0.069), and alpha-1-antitrypsin (359.27 vs. 522.44 ng/mL; p=0.264) were not significantly different between the groups. Intravitreal levels of tumor necrosis factor-alpha and tumor necrosis factor-beta were undetectable. Serum Amyloid P, C-reactive protein, platelet-derived growth factor A, platelet-derived growth factor B, interleukin-6, and interleukin-8 were correlated positively with vascular endothelial growth factor. Conclusions: Cellular mediators involved in neurodegeneration and inflammation demonstrated increased levels in the vitreous humor of patients with proliferative diabetic retinopathy and may be part of the pathogenesis of diabetic retinopathy.

RESUMO Objetivo: Comparar as concentrações intravítreas de mediadores celulares envolvidos na neurodegeneração, inflamação e angiogênese em pacientes com retinopatia diabética proliferativa e outras doenças vítreo-retinianas. Métodos: Um ensaio imunomagnético foi utilizado para medir os níveis vítreos do fator derivado do epitélio pigmentar, amilóide P sérico, proteína-C-reativa, complemento C4, e alfa-1-antitripsina, fator de crescimento do endotélio vascular, fator de crescimento derivado das plaquetas AA, fator de crescimento derivado das plaquetas BB, interleucina-6, interleucina-8, interleucina-10, fator de necrose tumoral alfa e beta em pacientes submetidos à vitrectomia 23-gauge para retinopatia diabética proliferativa ou outros diagnósticos (grupo controle). Resultados: Foram avaliados 55 pacientes, dos quais 24 tinham retinopatia diabética proliferativa e 31 tinham outros diagnósticos, incluindo hemorragia vítrea, descolamento de retina, buraco macular e membrana epirretiniana. Pacientes com retinopatia diabética proliferativa demonstraram níveis aumentados de amilóide P sérico (85,49 vs 31,38 ng/mL), proteína-C-reativa (59,89 vs 41,75 ng/mL), fator de crescimento do endotélio vascular (2.330,11 vs 554,25 pg/mL, p<0.001), fator de crescimento derivado das plaquetas-A: (127,32 vs 39,11 pg/mL), fator de crescimento derivado das plaquetas-B (29,37 vs 7,12 pg/mL), interleucina-6 (69,37 vs 33,58 pg/mL), interleucina-8 (175,25 vs 59,71 pg/mL) e interleucina-10 (3,70 vs 1,88 pg/mL), todos com p<0,004 quando comparados ao grupo controle. Níveis de fator derivado do epitélio pigmentar (30,06 vs 27,48 ng/mL; p=0,295), complemento C4 (570,78 vs 366,24 ng/mL; p=0,069), alfa-1 antitripsina (359,27 vs 522,44 ng/mL; p=0,264) não foram significativamente diferente entre os grupos. Níveis intravítreos de fator de necrose tumoral alfa e fator de necrose tumoral beta foram indetectáveis. O amilóide P sérico, a proteína C-reativa, o fator de crescimento derivado das plaquetas A e B, a interleucina-6 e a interleucina-8 correlacionaram-se positivamente com o fator de crescimento do endotélio vascular. Conclusões: Os medidores celulares envolvidos na neurodegeneração e inflamação demonstraram níveis aumentados no humor vítreo de pacientes com retinopatia diabética proliferativa e podem ser parte da patogênese da retinopatia diabética.

Enhanced S-cone syndrome: Clinical spectrum in Indian population

Purpose: Enhanced S-cone syndrome (ESCS), a rare disorder, is often misdiagnosed as other forms of retinal degenerations, which have a poorer prognosis than ESCS. The aim of this study is to report the varied clinical features of ESCS and distinguish it from other similar disorders. Methods: We retrospectively scrutinized the records of patients with confirmed diagnosis of ESCS and analyzed the findings. Results: We included 14 patients (age range 4–39 years) who were confirmed to have ESCS according to pathognomonic electroretinography (ERG) showing reduced photopic, combined responses, and 30 Hz flicker with reduced L, M cone responses and supernormal S cone responses. The disease presented in the 1st decade with night blindness and was almost stationary or minimally progressive. Mid-peripheral fundus changes in form of nummular pigmentary alterations, yellow punctate lesions, and macular schisis were noted. The vision ranged from 6/6 to 6/36 with follow-up ranging from 1month to 22 years. Conclusion: ESCS shows varied clinical features ranging from unremarkable fundus to pigment clumping and atrophic lesions. It has good prognosis with patients mostly maintaining their vision. ERG is diagnostic. More awareness and knowledge about this entity can help to differentiate it from other forms of night blindness.

Retinal dystrophies and variants in PRPH2 / Distrofias retinianas e variantes em PRPH2

ABSTRACT - This report presents three patients diagnosed with macular dystrophies with variants in PRPH2. Peripherin-2, the protein of this gene, is important in the morphogenesis and stabilization of the photoreceptor outer segment. Peripherin-2 deficiencies cause cellular apoptosis. Moreover, pathogenic variants in PRPH2 are associated with various diseases, such as pattern, butterfly-shaped pattern, central areolar, adult-onset vitelliform macular, and cone-rod dystrophies as well as retinitis pigmentosa, retinitis punctata albescens, Leber congenital amaurosis, fundus flavimaculatus, and Stargardt disease.

RESUMO - Este relato apresenta três pacientes com diagnóstico de distrofias maculares com mutações no PRPH2. Periferina 2, a proteína deste gene, é importante na morfogênese e estabilização do segmento externo dos fotorreceptores. Deficiências de periferina 2 causam apoptose celular. Além disso, variantes patogênicas no PRPH2 estão relacionadas a diferentes doenças, como distrofia padrão, distrofia padrão em asa de borboleta, distrofia central areolar, distrofia viteliforme do adulto, retinose pigmentar, distrofia de cones e bastonetes, retinite punctata albscens, amaurose congênita de Leber, fundus flavimaculatus e doença de Stargardt.

Analysis of Changes in Retinal Photoreceptors Using Optical Coherence Tomography in a Feline Model of Iodoacetic Acid-induced Retinal Degeneration

PURPOSE: We investigated structural changes in the retina by using optical coherence tomography (OCT) in a feline model of retinal degeneration using iodoacetic acid (IAA).METHODS: We examined 22 eyes of 11 felines over 2 years of age. The felines had fasted for 12 hours and were intravenously injected with IAA 20 mg/kg of body weight. OCT (Spectralis OCT) was performed at the point where the ends of the retinal vessels collected in the lateral direction from the optic nerve head and area centralis. Similarly, OCT was performed four times at 1-week intervals following injections, at which point the felines were sacrificed and histologic examinations were performed. Using OCT, the thickness of each layer of the retina was measured.RESULTS: The average body weight of the three male and eight female felines investigated in this study was 1.61 ± 0.19 kg. The mean total retinal thickness of the felines before injection was 221.32 ± 9.82 µm, with a significant decrease in the retinal thickness at 2, 3, and 4 weeks following injections of 186.41 ± 35.42, 174.56 ± 31.94, and 175.35 ± 33.84 µm, respectively (p = 0.028, 0.027, and 0.027, respectively). The thickness of the outer nuclear layer was 57.49 ± 8.03 µm before injection and 29.26 ± 17.87, 25.62 ± 13.88, and 31.60 ± 18.38 µm at 2, 3, and 4 weeks, respectively, after injection (p = 0.028, 0.028, 0.046, respectively).CONCLUSIONS: In a feline model of retinal degeneration using IAA, the total retinal thickness and the thickness of the outer nuclear layer were shown to decrease significantly on OCT.

Application of ultra wide angle fundus imaging in the screening of retinopathy in myopic adolescent retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the relationship between the prevalence of peripheral retinal degeneration and myopic degree by using the fort ultra wide angle scanning laser ophthalmoscope(Daytona P200T)for small, early and high middle school period of low, medium and high myopia students peripheral retinal scan.<p>METHODS: With method of stratified random cluster sampling, to select myopia students in two primary schools, one junior middle school and one senior high school in Mianyang. According to different degrees, the myopia was divided into low, medium and high myopia, with 300 people and 600 eyes respectively. Application of Daytona P200T in natural pupil downward fundus image acquisition, and then the senior ophthalmologist performed the fundus examination under the slit lamp after pupil dilation.<p>RESULTS: The prevalence of peripheral retinal degeneration was different among different refractive groups, and the higher the myopia, the higher the prevalence of peripheral retinal degeneration(χ2=75.76, <i>P</i><0.001). Comparison between different degree groups prevalence of peripheral retinal degeneration: frost degeneration(STD)no statistical difference between the three groups(χ2=5.66,<i> P</i>=0.059), lattice degeneration(LD), snail track degeneration(SD), non-oppressive whitening(WWP), cystic degeneration(CD), hiatal(DRP), pigment degeneration(RP)were differences among three groups. For further comparison, except WWP(χ2=9.385, <i>P</i>=0.002), low height both two(<i>P</i>>0.017). Moderately and highly group compared, in addition to the CD(χ2=8.525, <i>P</i>=0.004)and the RP(χ2=6.454, <i>P</i>=0.011), the rest were not tested statistically. Compared with the prevalence of peripheral retinal degeneration in different segments, retinal degeneration was observed in 34 eyes(5.7%)in primary school, 90 eyes(14.9%)in junior middle and 130 eyes(21.9%)in senior high. The prevalence of peripheral retinal degeneration increased with the increase of medical grade(χ2=64.79, <i>P</i><0.001). The prevalence of WWP and CD showed no statistical difference between junior middle school and primary school and senior high school(<i>P</i>>0.05). For further comparison, except LD(χ2=6.209, <i>P</i>=0.013)and STD(χ2=9.953, <i>P</i>=0.002), no statistical difference in the primary schools and junior middle, junior middle and senior high(<i>P</i>>0.017), statistical difference was detected between the primary schools and senior high school(<i>P</i><0.017).<p>CONCLUSION: The prevalence of peripheral retinal degeneration of myopia was positively correlated with myopia and learning period.

Development of a Post-vitrectomy Injection of N-methyl-N-nitrosourea as a Localized Retinal Degeneration Rabbit Model

Since genetic models for retinal degeneration (RD) in animals larger than rodents have not been firmly established to date, we sought in the present study to develop a new rabbit model of drug-induced RD. First, intravitreal injection of N-methyl-N-nitrosourea (MNU) without vitrectomy in rabbits was performed with different doses. One month after injection, morphological changes in the retinas were identified with ultra-wide-field color fundus photography (FP) and fundus autofluorescence (AF) imaging as well as spectral-domain optical coherence tomography (OCT). Notably, the degree of RD was not consistently correlated with MNU dose. Then, to check the effects of vitrectomy on MNU-induced RD, the intravitreal injection of MNU after vitrectomy in rabbits was also performed with different doses. In OCT, while there were no significant changes in the retinas for injections up to 0.1 mg (i.e., sham, 0.05 mg, and 0.1 mg), outer retinal atrophy and retinal atrophy of the whole layer were observed with MNU injections of 0.3 mg and 0.5 mg, respectively. With this outcome, 0.2 mg MNU was chosen to be injected into rabbit eyes (n=10) at two weeks after vitrectomy for further study. Six weeks after injection, morphological identification with FP, AF, OCT, and histology clearly showed localized outer RD - clearly bordered non-degenerated and degenerated outer retinal area - in all rabbits. We suggest our post-vitrectomy MNU-induced RD rabbit model could be used as an interim animal model for visual prosthetics before the transition to larger animal models.

Appilcation of polycaprolactone/collagen nanofibrous membranes in constituting tissue engineering retinal pigment epithelium / 中华实验眼科杂志

Objective@#To explore the potential of polycaprolactone (PCL)/gelatin nanofibrous composite membrane in constituting tissue engineering retinal pigment epithelium (RPE).@*Methods@#The embryonic stem cells (ESCs) were differentiated into RPE (ESC-RPE) cells by spontaneous differentiation methods.Flow cytometry was used to detect the expression of specific RPE markers in ESC-RPE cells.The nanofiber membrane of PCL and PCL/gelatin nanofibrous composite membrane were prepared by electrospinning.The topography and contact angle of the two membranes were detected.The viability of ESC-RPE cells treated by the extracts of the two kinds of membranes was detected by cell counting kit-8 (CCK-8)method.After the ESC-RPE cells were cultured on the PCL/gelatin nanofibrous composite membrane, immunostaining was used to detect the expression of specific RPE markers of tissue engineering RPE.@*Results@#ESC-RPE cells were negative for pluripotent marker OCT4, but positive for microphthalmia-associated transcription factor (MITF), RPE65 and Bestrophin.Both the nanofiber membrane of PCL and PCL/gelatin nanofibrous composite membrane were porous and the contact angle were (97.2±3.1)° and (13.6±2.4)°, respectively.The extracts of the two kinds of membranes showed no significant effect on the growth of ESC-RPE cells.The tissue engineering RPE based on PCL/gelatin nanofibrous composite membrane positively expressed MITF and ZO-1.@*Conclusions@#PCL/gelatin nanofibrous composite membrane shows good hydrophilicity and biocompatibility.Besides, the membrane is favor for the growth of ESC-RPE cells and holds the potential to constitute tissue engineering RPE.

The application of the Daytona ultra-widefield retinal imaging device in preoperative fundus examination before refractive surgery / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the effectiveness of the Daytona ultra-widefield retinal imaging device in preoperative fundus examination before refractive surgery.<p>METHODS: A consecutive series of 624 eyes in 312 patients intended to performing refractive surgery with myopia were examined fundus by the Daytona ultra-widefield retinal imaging device before dilating pupil. After dilating pupil, the non-contact slit lamp lenses and three-mirror contact lens were used to examine fundus again.<p>RESULTS: Average examination time of the Daytona and non-contact slit lamp lenses was 5.38±1.25min and 7.25±3.23min respectively, there was no statistical significant difference(<i>P</i><0.001). The Daytona detected peripheral retinal pathology in 107 eyes(17.1%)and the non-contact slit lamp lenses detected peripheral retinal pathology in 108 eyes(17.3%), 126 lesions were detected and there was no statistical significant difference between the two methods(<i>P</i>=1.000).<p>CONCLUSION: The Daytona has non-contact, shorter time and ultra-widefield view of the retina which is a reliable method in examining the retinal pathology without mydriasis.

Effect of Phosphorylated-Extracellular Regulated Kinase 1/2 Inhibitor on Retina from Light-induced Photoreceptor Degeneration / 中华医学杂志(英文版)

Background@#The demonstrated role of mitogen-activated protein kinase (MAPK) in both cell apoptosis and the inflammation pathway makes it an attractive target for photoreceptor protection. The aim of this study was to investigate the protective effects of MAPK antagonists against photoreceptor degeneration and retinal inflammation in a rat model of light-induced retinal degeneration.@*Methods@#Sprague Dawley rats were treated with intravitreal injections of MAPK antagonists, inhibitors of p-P38, phosphorylated-extracellular regulated kinase (p-ERK) 1/2, and p-c-Jun N-terminal kinase (JNK) just before they were assigned to dark adaptation. After dark adaptation for 24 h, rats were exposed to blue light (2500 lux) in a light box for 24 h, and then returned to the normal 12-h light/12-h dark cycle. Samples were collected at different time points. MAPK expression during light exposure was examined with immunofluorescence. Photoreceptor death was detected with histopathology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of retinal p-ERK1/2, caspase 3, activated caspase 3, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β was examined by Western blotting. Differences between groups were evaluated using unpaired one-way analysis of variance and least significant difference post hoc tests.@*Results@#MAPKs (P38, ERK1/2, and p-JNK) were phosphorylated and activated in the light injury groups, compared with normal group, and their expressions were mainly elevated in the outer nuclear layer (ONL). Among the selected MAPK antagonists, only the p-ERK1/2 inhibitor attenuated the loss of photoreceptors and the thinning of ONL in light injury groups. Besides, p-ERK1/2 inhibitor refrained light-induced photoreceptor apoptosis, which was presented by TUNEL positive cells. Light injury significantly increased the expression of p-ERK1/2 (1.12 ± 0.06 vs. 0.57 ± 0.08, t = 9.99, P < 0.05; 1.23 ± 0.03 vs. 0.57 ± 0.08, t = 11.90, P < 0.05; and 1.12 ± 0.12 vs. 0.57 ± 0.08, t = 9.86, P < 0.05; F = 49.55, P < 0.001), and induced caspase 3 activating (0.63 ± 0.06 vs. 0.14 ± 0.05, t = 13.67, P < 0.05; 0.74 ± 0.05 vs. 0.14 ± 0.05, t = 16.87, P < 0.05; and 0.80 ± 0.05 vs. 0.14 ± 0.05, t = 18.57, P < 0.05; F = 100.15, P < 0.001), compared with normal group. The p-ERK1/2 inhibitor significantly reduced p-ERK1/2 overexpression (0.61 ± 0.06 vs. 1.12 ± 0.06, t = -9.26, P < 0.05; 0.77 ± 0.06 vs. 1.23 ± 0.03, t = -8.29, P < 0.05; and 0.68 ± 0.03 vs. 1.12 ± 0.12, t = -7.83, P < 0.05; F = 49.55, P < 0.001) and downregulated caspase 3 activating (0.23 ± 0.04 vs. 0.63 ± 0.06, t = -11.24, P < 0.05; 0.43 ± 0.03 vs. 0.74 ± 0.05, t = -8.86, P < 0.05; and 0.58 ± 0.03 vs. 0.80 ± 0.05, t = -6.17, P < 0.05; F = 100.15, P < 0.001), compared with light injury group. No significant change in the total level of caspase 3 was seen in different groups (F = 0.56, P = 0.75). As for inflammation, light injury significantly increased the expression of TNF-α (0.42 ± 0.04 vs. 0.25 ± 0.05, t = 5.99, P < 0.05; 0.65 ± 0.03 vs. 0.25 ± 0.05, t = 14.87, P < 0.05; and 0.86 ± 0.04 vs. 0.25 ± 0.05, t = 22.58, P < 0.05; F = 160.27, P < 0.001) and IL-1β (0.24 ± 0.01 vs. 0.19 ± 0.02, t = 2.33, P < 0.05; 0.35 ± 0.02 vs. 0.19 ± 0.02, t = 7.97, P < 0.05; and 0.48 ± 0.04 vs. 0.19 ± 0.02, t = 14.69, P < 0.05; F = 77.29, P < 0.001), compared with normal group. P-ERK1/2 inhibitor significantly decreased the overexpression of TNF-α (0.22 ± 0.02 vs. 0.42 ± 0.04, t = -7.40, P < 0.05; 0.27 ± 0.02 vs. 0.65 ± 0.03, t = -14.27, P < 0.05; and 0.33 ± 0.03 vs. 0.86 ± 0.04, t = -19.58, P < 0.05; F = 160.27, P < 0.001) and IL-1β (0.13 ± 0.03 vs. 0.24 ± 0.01, t = -5.77, P < 0.05; 0.17 ± 0.01 vs. 0.22 ± 0.02, t = -9.18, P < 0.05; and 0.76 ± 0.05 vs. 0.48 ± 0.04, t = -13.12, P < 0.05; F = 77.29, P < 0.001), compared with light injury group.@*Conclusion@#The p-ERK1/2 inhibitor might protect the retina from light-induced photoreceptor degeneration and retinal inflammation.

Contribution of Borneolum syntheticum to the Intervention Effect of Liuwei Dihuang Pill () on Experimental Retinal Degeneration / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the contribution of Borneolum syntheticum to the intervention effect of Liuwei Dihuang Pill (, LDP) on experimental retinal degeneration, and initially investigate the mechanism of Borneolum syntheticum as meridian-lead-in drug.</p><p><b>METHODS</b>A total of 180 sodium iodateinduced retinital degeneration rats were randomly divided into three groups, including distilled water group, LDP group, and LDP+Borneolum syntheticum (LDP+BS) group. Twenty normal rats were fed regularly without any treatment as normal control. On day 7 and 14 after treatment, histopathological study and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) test were performed to evaluate the retinopathy. Claudin-5 expression at blood-retina barrier (BRB) was detected by Western blot at different time points from 0.5 to 8 h after gavage.</p><p><b>RESULTS</b>On day 7 and 14 after treatment, the retinal lesion grades were significantly different among the three groups (P<0.05). The grade in the LDP+BS group was significantly less than the LDP and distilled water groups (both P<0.05), no significant difference was observed between the LDP and distilled water groups (P>0.05). The apoptosis rates in the LDP+BS group was significantly less than the distilled water and LDP groups (both P<0.05), while there was no significant difference between LDP and distilled water groups (P>0.05). Expression of claudin-5 in LDP+BS group was significantly less than the other two groups at 0.5, 1 and 2 h after gavage (P<0.05). There was no apparent difference among the three groups at 4 and 8 h after gavage (P>0.05).</p><p><b>CONCLUSION</b>Borneolum syntheticum could strengthen the effect of LDP on experimental retinal degeneration, indicated that Borneolum syntheticum might play the role of meridian-lead-in drug in the formula. The mechanism may be due to Borneolum syntheticum could promote the physiologically openness of bloodretina barrier through transiently affecting the expression of claudin-5.</p>