1.Research advances on the impact of obstructive sleep apnea on ocular fundus diseases
Xueyi PANG ; Yunshan CAO ; Yan ZHANG
Chinese Journal of Experimental Ophthalmology 2025;43(1):80-86
Obstructive sleep apnea (OSA) is a common sleep disorder that is closely associated with ocular fundus diseases such as glaucomatous optic neuropathy, nonarteritic anterior ischemic optic neuropathy, diabetic retinopathy, central serous chorioretinopathy and retinal vein occlusion.The main mechanisms by which OSA affects fundus diseases include intermittent hypoxia, activation of sympathetic nervous system, systemic oxidative stress, and inflammatory response, but the specific mechanisms require further investigation.The therapeutic modality such as continuous positive airway pressure can alleviate the symptoms of ocular fundus diseases in the patients with OSA and reduce the risk of disease progression.Therefore, clinicians should recognize the relationship between OSA and fundus diseases, understand the impact of OSA on these diseases, and achieve early diagnosis and treatment of the OSA-associated fundus diseases to reduce the risk of severe visual impairment and blindness.
2.Influencing factors of recurrence of macular edema secondary to retinal vein occlusion
Chinese Journal of Experimental Ophthalmology 2025;43(1):87-91
Retinal vein occlusion (RVO) is a common retinal vascular disease, and macular edema (ME) is the most common cause of visual impairment in eyes with RVO.Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has been advocated as a first-line therapy for ME secondary to RVO.After anti-VEGF treatment, the patient's visual function recovers well in the short term, but the long-term efficacy is unstable and the recurrence rate of ME is high.Therefore, it is of great clinical value to predict the factors influencing the recurrence of ME, which would help determine which patients should receive frequent follow-up and more aggressive treatment to achieve better clinical outcomes.In this paper, the influencing factors of recurrence of ME secondary to RVO are summarized, including disorganization of retinal inner layer, change in the macular microvascular structure, change in choroid thickness, the non-perfusion area between different areas of the retina, inflammatory cytokines, retinal blood flow and blood flow velocity, etc., which can provide an important basis for patient counseling, clinical diagnosis and treatment and prognostic follow-up.
3.Regulatory effect of electroacupuncture on visual cortex plasticity in adult amblyopic mice and its mechanism
Wen LI ; Jing FU ; Chanyuan WANG ; Jing TANG ; Yuting LIU ; Yulin LUO
Chinese Journal of Experimental Ophthalmology 2025;43(2):106-113
Objective:To investigate the regulatory effect of electroacupuncture on visual cortex plasticity in adult amblyopic mice and its mechanism.Methods:Forty-eight SPF male healthy 3-week-old Kunming mice were randomly divided into a normal control group, a monocular form deprivation (MD) group, and an electroacupuncture intervention group by the random number table method, with 16 mice in each group.Except for the normal control group, mice in the other groups had their right eyelids sutured for two weeks to establish an adult MD amblyopia model.The electroacupuncture intervention group received electroacupuncture stimulation at three acupoints, Taiyang (EX-HN5), Jingming (BL1), and Fengchi (GB20) for four weeks at five weeks of age.The subjective visual function (paw probing success rate) of each group of mice was measured at five and nine weeks of age, respectively.At nine weeks of age, the changes in flash-visual evoked potential (F-VEP) of mice in each group was detected.The expression of plasticity related proteins synaptophysin (SYP), synaptic protein 1 (SYN1), neurite overgrowth inhibitor A (Nogo-A), and Nogo receptor (NgR) proteins in the contralateral cortex of the deprived mouse eyes was detected by Western blot.Expression of early growth response gene 1 (Egr-1) in the visual cortex of mice was detected by immunohistochemical staining.This study was approved by the Animal Ethics Committee of Hunan Children's Hospital (No.HCHDWLL-2022-17), and the management and use of animals were in accordance with the Laboratory Animal Management and Use Guide of Hunan Children's Hospital.Results:At nine weeks of age, the success rates of paw probing in the normal control group, MD group, and electroacupuncture intervention group were (71.69±10.60)%, (25.54±10.09)%, and (58.25±8.39)%, respectively, with a statistically significant overall difference ( F=5.987, P=0.006).Among them, the success rate of paw probing was significantly lower in the MD group than in the normal control group, and the electroacupuncture intervention group was significantly higher than in the MD group (both P<0.05).There was a significant overall difference in P2 wave amplitude in F-VEP examination among different groups of mice ( F=63.710, P<0.001), with lower P2 wave amplitude in the deprived eye of the MD group than in the normal control group and the electroacupuncture intervention group, and the differences were statistically significant (both P<0.001).There were significant differences in the expression levels of SYP and SYN1 proteins in the contralateral cortex of the deprived mouse eyes ( F=5.451, 3.871; both P<0.05).The relative expression levels of SYP and SYN1 proteins were significantly lower in the MD group than in the normal control group and electroacupuncture intervention group (all P<0.05).There were significant differences in levels of Nogo-A and NgR proteins in the contralateral cortex of the deprived mouse eyes ( F=4.188, 3.942, both P<0.05).The relative expression levels of Nogo-A and NgR proteins were significantly higher in the MD group than in the normal control group and the electroacupuncture intervention group (all P<0.05).The immunohistochemical staining results showed that compared with the normal control group, the MD group mice had a decrease in the expression of Egr-1 in the contralateral cortical neurons of the deprived eye, and the brown neuron protrusions were indistinguishable.Compared with the MD group, the electroacupuncture intervention group showed significant positive cell expression in the contralateral cortical area of the deprived eye, but the expression intensity was weaker than that of the normal control group. Conclusions:Electroacupuncture treatment of Taiyang (EX-HN5), Jingming (BL1), and Fengchi (GB21) acupoints can reactivate the plasticity of the visual cortex in adult amblyopic mice and improve their visual function.The mechanism may be related to the regulation of Nogo-A/NgR signaling pathway.
4.Progress in biomaterials of artificial Bruch membrane in RPE tissue engineering complex
Chinese Journal of Experimental Ophthalmology 2025;43(3):276-282
Degenerative retinal diseases such as age-related macular degeneration (AMD) may cause permanent visual loss.Although anti-vascular endothelial growth factor (anti-VEGF) and steroid injection can effectively treat early lesions of wet AMD, there is still a lack of treatment for dry AMD and late geographic atrophy.Retinal pigment epithelium (RPE) is essential to maintain visual function, and its dysfunction is associated with retinal degenerative diseases.RPE transplantation can replace the diseased cells to ensure the normal function of RPE and maintain retinal homeostasis.However, studies have shown that the short-term results of cell injection alone are difficult to maintain.Successful cell transplantation therapy must simultaneously improve the dysfunctional RPE cells and extracellular microenvironment, and the research and development of biomaterial scaffolds has become a key breakthrough.Tissue engineering offers a prospect for repairing retinal damage and restoring its function.Functional RPE monolayer transplantation needs to remodel the tight arrangement of polarized RPE, and tissue engineering can realize the growth of RPE on the biomaterial scaffold artificial Bruch membrane.Combined with scaffold culture, cell growth and transplantability can be better.This paper reviews the research status of artificial Bruch membrane materials supporting RPE culture, lists typical cases, and summarizes the specific classification, mechanical and biological characteristics of RPE scaffold materials to lay the foundation for developing new materials and promoting the clinical application of artificial Bruch membrane in RPE transplantation.
5.Effects and mechanisms of BMP7 mimetic peptide THR123 on regulating proliferative vitreoretinopathy and retinal pigment epithelial-mesenchymal transition
Haipei YAO ; Fang WANG ; Yulan WANG
Chinese Journal of Experimental Ophthalmology 2025;43(1):18-26
Objective:To investigate the role of bone morphogenetic protein (BMP) 7 peptidomimetics THR123 in the regulation of proliferative vitreoretinopathy (PVR) and epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells.Methods:Primary human RPE cells were isolated from donor eyes.The RPE cells was cultured for 48 hours with conventional medium, medium containing 10 ng/ml transforming growth factor-β2 (TGF-β2), medium containing 10 ng/ml TGF-β2 and 5 μg/ml THR123, respectively, serving as negative control group, TGF-β2 stimulation group and THR123-treated group.The relative protein expression levels of E-cadherin, α-smooth muscle actin (α-SMA), fibronectin (FN) activin receptor-like kinase-2 (ALK2) and Snail family zinc finger transcription factor 1, Snail1) were detected by Western blot analysis in each group.RPE cell contractile function was detected by collagen gel contraction assay.RPE cell migration function was detected by transwell assay.RPE cell polarity was detected by transepithelial resistance.For the in vivo model, the rabbit PVR model was established by intravitreal injection of RPE cells and cytokine platelet-derived growth factor.The PVR rabbits were randomly divide into PVR group, 0.5 μg/ml THR123 group and 5 μg/ml THR123 group, and were intravitreally injected with corresponding concentration of THR123 on the day of modelling and 7 days after modelling.The fundus conditions of rabbits were observed every 7 days.Retinal detachment was checked by B-scan ultrasonography every 7 days, and PVR grading was performed on 14 and 28 days after modelling.On day 28 after modelling, the rabbit was sacrificed by air embolism and the eyeball was enucleated.Hematoxylin-eosin (HE) staining and α-SMA immunofluorescence staining were performed to compare the differences in PVR progression among groups.In the LDN inhibition group, BMP receptor inhibitor LDN193189 was added to primary RPE cells and the expression of EMT markers and cell functional differences of RPE cells were compared between negative control group and LDN inhibition group.Small interfering RNA of control and Snail1 was transfected into RPE cells of siNC+ TGF-β2 group and siSnail1+ TGF-β2 group, respectively, and the differences in EMT markers and function of RPE cells were compares.The protocol involving human specimens, cells and animals in this study was opproved by the Medical Ethics Committee of Shanghai General Hospital (No.2021SQ057). Results:There were statistically significant differences in gel contraction ratio, transepithelial resistance and relative expressions of E-Cadherin, FN and α-SMA proteins among the negative control group, TGF-β2 stimulation group and THR123-treated group ( F=28.38, 136.30, 38.50, 2.53, 53.54; all P<0.01).Compared with the negative control group and THR123-treated group, the gel contraction ratio, transepithelial resistance, and relative expression of E-cadherin in the TGF-β2 stimulation group decreased, and the relative expression of α-SMA and FN increased, with statistically significant differences (all P<0.01).On day 28 after modeling, the PVR grades in the PVR group, 5 μg/ml THR123 group and 5 μg/ml THR123 group were 4.00±0.45, 2.80±0.37, 1.80±0.37, respectively, with a statistically significant difference among groups ( F=7.583, P=0.007).The PVR grade of rabbit eyes was significantly lower in the 5 μg/ml THR123 group than in the PVR group ( P<0.05).HE staining showed that the number of preretinal proliferative membranes was less in the 5 μg/ml THR123 group than in the PVR group and the 0.5 μg/ml THR123 group, and no retinal detachment was found.Immunofluorescence staining showed that the expression of α-SMA in vitreous cavity and retina was significantly lower in the 5 μg/ml THR123 group than in the PVR group and the 0.5 μg/ml THR123 group.Compared with the negative control group and THR123-treated group, the relative expression of ALK2 protein in the TGF-β2 stimulation group was significantly decreased, and the relative expression of Snail1 protein was significantly increased (all P<0.01).Compared with the negative control group, the gel contraction ratio, transepithelial resistance and relative expression of E-cadherin protein in the LDN inhibition group were significantly reduced, and the relative expression of FN, α-SMA and Snail1 proteins were significantly increased (all P<0.01).Compared with the siNC+ TGF-β2 group, the gel contraction ratio and the relative expression of E-cadherin protein in the siSnail1+ TGF-β2 group were significantly increased, and the relative expression of FN, α-SMA and Snail1 proteins were significantly decreased (all P<0.05). Conclusions:THR123 can activate the BMP pathway to inhibit Snail1, thereby inhibiting the EMT process in RPE cells and PVR occurrence.It is expected to provide potential targets for PVR drug therapy.
6.Characteristics of crystalline lens tilt and decentration distribution and related factors in patients with age-related cataract
Yifen WU ; Ying ZHANG ; Yong WANG
Chinese Journal of Experimental Ophthalmology 2025;43(3):233-240
Objective:To investigate the characteristics of crystalline lens tilt and decentration distribution in age-related cataract patients and analyze the related factors.Methods:A cross-sectional study was conducted.A total of 585 consecutive patients (1 170 eyes) with bilateral age-related cataracts over the age of 50 were enrolled at Aier Eye Hospital of Wuhan University from January 2022 to March 2022.Bilateral crystalline lens tilt and decentration magnitude and direction were measured by swept-source anterior segment optical coherence tomography.Corneal curvature, white-to-white corneal diameter, anterior chamber depth, lens thickness and axial length were measured using a swept-source optical coherence tomography biometer.The correlation of tilt magnitude and decentration magnitude of crystalline lens was assessed by Pearson linear correlation analysis.The correlation of tilt direction and decentration direction of crystalline lens was assessed by Spearman rank correlation analysis.The influence of age and ocular biometric parameters on crystalline lens tilt and decentration was analyzed by multiple linear regression analysis.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Aier Eye Hospital of Wuhan University (No.2022IRBKY0617).All patients signed the informed consent form before any medical examination.Results:The mean tilt magnitude was (4.69±1.59)°, of which 6.7% had a tillt ≥7°, and the direction was mainly toward the inferotemporal side with a mirror symmetry between both eyes.The mean decentration magnitude was (0.19±0.11)mm, of which 5.3% had a decentration ≥0.4 mm, and the direction was mainly towards the temporal side.The crystalline lens tilt magnitude was positively correlated with decentration magnitude ( r=0.422, P<0.001) and the crystalline lens tilt direction was positively correlated with decentration direction ( rs=0.432, P<0.001).There was no significant difference in crystalline lens tilt magnitude between both eyes ( t=0.487, P=0.626), and the crystalline lens decentration was significantly greater in the right eye than in the left eye, with statistically significant difference ( t=2.563, P=0.011).There was no significant difference in crystalline lens tilt and decentration between male and female ( t=1.500, 1.566; both P>0.05).The crystalline lens tilt magnitude was significantly greater in 60-69 years, 70-79 years and 80-89 years groups than in 50-59 years group, and the crystalline lens decentration magnitude was significantly greater in the 80-89 years group than in the 60-69 years group (all P<0.05).The crystalline lens tilt magnitude was smaller in the axial length ≥25 mm group than in the <22 mm group and the 22-<25 mm group, and the differences were statistically significant (both P<0.001).There was no significant difference in crystalline lens decentration magnitude among different axial length groups ( F=1.433, P=0.239).The multiple linear regression analysis revealed that the effects of anterior chamber depth ( B=-0.474, t=-2.115, P=0.035), axial length ( B=-0.258, t=-9.324, P<0.001) and crystalline lens decentration ( B=5.646, t=11.234, P<0.001) on crystalline lens tilt were statistically significant.The influence of lens thickness ( B=-0.032, t=-2.402, P=0.017), axial length ( B=0.010, t=4.406, P<0.001) and crystalline lens tilt ( B=0.032, t=11.234, P<0.001) on crystalline lens decentration were statistically significant. Conclusions:Among age-related cataract patients aged 50 and above, 6.7% have crystalline lens tilt ≥7°, and 5.3% have crystalline lens decentration ≥0.4 mm.The older the age, the greater the crystalline lens tilt and decentration.The shorter the axial length and the shallower the anterior chamber, the greater the tilt of the lens.The greater the tilt magnitude and decentration, the greater the decentration magnitude and decentration.
7.Inducing effect of advanced glycation end products on ferroptosis in human retinal pigment epithelial cells
Jun TONG ; Zhenggao XIE ; Huangyi LEI ; Yanbo BAO ; Zhenping HUANG
Chinese Journal of Experimental Ophthalmology 2025;43(1):32-37
Objective:To investigate the effect of advanced glycation end products (AGEs) on ferroptosis in human retinal pigment epithelium (RPE) cell cultured in vitro. Methods:ARPE-19 cell lines were cultured in DMEM medium containing 10% fetal bovine serum (FBS), and the 3rd to 6th generations of cells were used for further study.Cell activity was detected by using the cell counting kit 8 after ARPE-19 were cultured with AGEs at 0, 50, 100, 200, 400 μg/ml for 48 hours.The cells were cultured with 200 μg/ml AGEs for 48 hours.Cell lipid peroxidation level was measured by Lipid Peroxidation Assay Kit (Bodipy 581/591 C11) combined with flow cytometry.The relative mRNA and protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were determined by quantitative real-time PCR (qRT-PCR) and Western blot.The morphology of mitochondria was observed by transmission electron microscope.Results:The activity of ARPE-19 cells decreased with increasing AGEs concentration, and the overall difference of ARPE-19 activity among 0, 50, 100, 200, 400 μg/ml AGEs groups was statistically significant ( F=6.21, P<0.01).The cell activity of ARPE-19 cells in 200 and 400 μg/ml AGEs groups was lower than that in control group (both P<0.05).Flow cytometry showed that the fluorescence intensity in AGEs group was 622.0±11.3, which was significantly higher than 487.7±12.8 in control group ( t=6.809, P=0.002).qRT-PCR showed that the mRNA and protein relative expression levels of SLC7A11 and GPX4 were lower in AGEs group than those in control group (mRNA: t=3.72, 7.14, both P<0.05; protein: t=6.20, 5.15, both P<0.05).Transmission electron microscopy showed that mitochondria in AGEs group shrank with significantly reduced volume, decreased mitochondrial cristae, and increased mitochondrial membrane density. Conclusions:AGEs can induce ferroptosis in ARPE-19 cultured in vitro.
8.Clinical manifestations and risk factors of congenital cataract in infants
Bohao WANG ; Yilin PANG ; Heng MIAO ; Yongzhen BAO
Chinese Journal of Experimental Ophthalmology 2025;43(3):250-255
Objective:To compare the clinical manifestations of congenital cataracts across different age groups and investigate the clinical characteristics and risk factors associated with infantile congenital cataracts.Methods:A cross-sectional study was conducted.The medical records of 156 children aged under 6 years diagnosed with congenital cataracts at Peking University People's Hospital were collected.Participants were divided into two groups, the infantile group (107 cases) and the non-infantile group (49 cases) according to whether the first diagnosis was ≤12 months.Clinical presentations were compared between the two groups.Risk factors for infantile congenital cataracts was analyzed by multivariate logistic regression.This study adhered to the Declaration of Helsinki, and the study protocol was reviewed and approved by the Ethics Review Committee of Peking University People's Hospital (No.2023PHB150-001).Results:The incidence rate of both eyes in the infantile group was 80.37%(86/107), which was significantly higher than 48.98%(24/49) in the non-infantile group ( χ2=15.931, P<0.001).The proportion of chief complaint of leucocoria in the infantile group was 87.85%(94/107), which was significantly higher than 44.90%(22/49) in the non-infantile group ( χ2=32.521, P<0.001).There were significant differences in the proportion of gestational age, birth weight, and neonatal oxygen therapy between the two groups ( χ2=13.300, 8.363, 13.283; all P<0.05).Multivariate logistic regression analysis showed that preterm birth ( OR=2.901, P=0.026), low birth weight ( OR=3.316, P=0.047), history of oxygen inhalation ( OR=3.040, P=0.012), and a family history of cataracts ( OR=14.224, P=0.013) were the main risk factors for congenital cataracts in infancy.The age of first diagnosis in children diagnosed with congenital cataracts through hospital screening was younger than that through parent observation ( Z=1 416.00, P=0.045). Conclusions:Infantile congenital cataracts predominantly present in both eyes with leukocoria as main manifestation.Preterm birth, low birth weight, neonatal oxygen exposure, and family history of cataracts are risk factors for infantile congenital cataracts.Systematic hospital screening is essential for the early detection of congenital cataracts in infants.
9.Comparison of intraocular stability of intraocular lenses with different haptic designs after cataract surgery and its influencing factors
Shengnan WANG ; Xiao LI ; Yingjie CHI ; Yawei LI ; Guangying ZHENG
Chinese Journal of Experimental Ophthalmology 2025;43(3):256-262
Objective:To observe and analyze the intraocular stability of intraocular lens (IOL) with different haptic designs after cataract surgery by swept-source optical coherence tomography (SS-OCT) and analyze its influencing factors.Methods:A cohort study was conducted.Medical records of 130 consecutive patients (130 eyes) diagnosed with age-related cataract, who underwent phacoemulsification and IOL implantation at The First Affiliated Hospital of Zhengzhou University from August 2021 to August 2022 were collected.According to the type of IOL implanted, the patients were divided into four groups, L-haptic group with 34 cases (34 eyes), modified C-haptic group with 30 cases (30 eyes), plate-haptic group with 36 cases (36 eyes), four-haptic group with 30 cases (30 eyes).Before surgery, the patient's axial length and IOL diopter were measured with an optical biometer, and the angle kappa and angle alpha were measured with corneal topography.At 3 months after surgery, the anterior chamber depth, decentration and tilt of IOL, the space area between IOL and posterior capsule (AREAP) of the four groups were measured using SS-OCT.And anterior chamber depth changes and diopter changes were calculated.This study complied with the Declaration of Helsinki.The study protocol was reviewed and approved by the Medical Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2022-KY-1222-002).All subjects were aware of the purpose and significance of this study and voluntarily signed the informed consent form.Results:The average decentration and tilt of the modified C-haptic, L-haptic, plate-haptic, and four-haptic IOL decreased successively at 3 months after surgery, with no statistically significant differences ( H=7.055, F=5.162; all P>0.05).The postoperative anterior chamber depth, the anterior chamber depth change, the diopter change and the AREAP of the modified C-haptic, L-haptic, plate-haptic, and four-haptic IOL decreased successively at 3 months after surgery, and the differences were statistically significant (all P<0.05).Preoperative angle kappa was positively correlated with postoperative 3-month IOL tilt ( r=0.554, P<0.001).Preoperative angle alpha was positively correlated with postoperative 3-month IOL tilt ( r=0.469, P<0.001).The multiple linear regression model constructed with preoperative angle kappa and preoperative angle alpha as independent variables and IOL tilt as dependent variable was statistically significant ( F=39.526, P<0.001, R2=0.384).For every 1 mm increase in preoperative angle kappa, postoperative tilt will increase by 0.438°; for every 1 mm increase in preoperative angle alpha, postoperative tilt will increase by 0.300°. Conclusions:All four IOLs with different haptic designs have good horizontal centering stability.The plate-haptic and the four-haptic IOLs have superior vertical stability compared to L-haptic and modified C-haptic designs.Preoperative angles kappa and alpha can be used as indicators to predict postoperative IOL tilt.
10.Advance on the posterior lenticonus
Lingshan LU ; Chao ZHENG ; Jian ZHOU
Chinese Journal of Experimental Ophthalmology 2025;43(3):263-270
Posterior lenticonus (PLC) is a type of congenital lens disease in the morphology of spherical or conical bulging of the posterior capsule of the lens.It occurs predominantly in unilateral and sporadic, and the bilateral case is often inherited in type of autosomal dominant or X-chromosome linked inheritance.The mutations of EPHA2 are the major known causes of PLC until now.Although researchers have proposed hypotheses that the formation of PLC are related to weak posterior capsule, excessive growth of lens epithelial cells and traction of pigment tissue based on the clinical manifestations of PLC, the pathogenesis of PLC is not elucidated.The animal models associated with PLC can be roughly divided into posterior capsule protrusion and posterior capsule rupture combined with cataract.The clinical manifestations of PLC are various with main symptoms including leukocoria, strabismus, photophobia, and decreased vision.Preoperative examinations by slit-lamp microscopy, ultrasound biomicroscopy, Pentacam can detect abnormal morphological changes of the posterior capsule of lens.Intraoperative characteristic manifestations such as fish-tail and jelly-fish sign can be used to diagnose PLC.When PLC is combined with lens opacity, cataract extraction combined with posterior continuous curvilinear capsulorrhexis or posterior capsule cutting with vitrectomy is the main surgical treatment.Intraocular lens implantation or glass wear is used to correct the aphakic eyes.Postoperative amblyopia training is crucial for improving visual function.

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