Rare micropupil secondary to congenital cataract surgery favoring the development of the affected eye: a case report.

BACKGROUND: Congenital microcoria has been extensively reported and usually leads to visual dysfunction or blindness. However, micropupil development secondary to cataract surgery has never been reported. Here, we describe a rare case of micropupil development in infancy that occurred secondary to combined cataract extraction and intraocular lens implantation for treatment of congenital cataract. When the patient reached adulthood, the affected eye not only gained good vision but also showed better ocular development and refractive status than the fellow eye. CASE PRESENTATION: A 17-year-old boy presented to our outpatient clinic with decreased vision in his left eye related to congenital cataract surgery at 6 months of age. The affected eye had exhibited a pinhole pupil since the third month postoperatively. The condition had been managed with observation and regular monocular occlusion treatment. Upon presentation to our clinic, the best-corrected visual acuity (BCVA) in his fellow eye was 0.0 logMAR(20/20) with a refraction of - 5.75 diopters cylinder/-2.25 diopters sphere, and the BCVA in his affected eye was 0.5 logMAR(20/40) with a refraction of 0.00 diopters. Ophthalmic examination of the affected eye revealed a pinhole pupil (approximately 0.5 mm) with high light reflex sensitivity but no response to pupil-dilating drugs. The patient underwent pupilloplasty of the affected eye under corneal surface anesthesia. Postoperative examination revealed better ocular development in the affected eye than in the fellow eye (axial length: 24.21 vs. 27.02 mm, respectively) as well as better refractive status in the affected eye (BCVA of 0.0 logMAR(20/20) with a refraction of - 2.23 diopters cylinder/-3.00 diopters sphere vs. 0logMAR(20/20) with a refraction of -5.75 diopters cylinder/-2.25 diopters sphere). CONCLUSIONS: We have reported a rare case of micropupil development secondary to congenital cataract surgery, which is an uncommon complication, especially in children. However, unlike congenital microcoria, the secondary pinhole pupil may have reduced imaging haze and halos, possibly favoring the development of the affected eye. This case provides further insight into the treatment of congenital cataract.

Effects of Long-Term Simulated Weightlessness on Retinal Microcirculation and Visual Electrophysiology.

Objective: To investigate the mechanisms of ocular injuries in astronauts due to gravity deficit by examining changes in retinal microcirculation and visual electrophysiology in macaques subjected to simulated weightlessness. Methods: The head-down recumbency of macaques was used to simulate the movement of blood to the side of the head that occurs without microgravity. Head-down recumbency was performed with the head tilted downwards at a recommended angle of 10°. The macaques in the control group were similarly tethered to the rope but could be held in a normal position. The whole experiment lasted for 6 weeks and retinal microcirculation and visual electrophysiology information was collected at weeks 0, 3 and 6. Results: The retinal microcirculation of macaques was affected by 3 weeks of weightlessness. This includes morphological changes, such as dilation and tortuosity of the retinal microvasculature in macaques at day 21. OCT and OCTA results showed an increase in retinal and choroidal thickness and a significant decrease in vessel length density within 6×6 mm of the macula. Sustained simulated weightlessness (42 days) significantly exacerbated retina-related damage. This was evidenced by a significant decrease in the perfusion density of microcirculatory vessels, such as the macular 3×3 mm mesial vessels and the macular 6*6 mm central and medial vessels. The FAZ density in the macula 3×3 mm area began to increase. Retinal oxygen saturation testing showed a slight increase in arterial oxygen saturation. Simultaneous changes in visual electrophysiology occurred, including a significant decrease in a- and b-wave amplitudes on the dark-vision electroretinogram and a significant decrease in the amplitude of the bright-vision negative wave response. The peak timing of the flash visual evoked potential component P1 was significantly delayed compared to its baseline and time-matched control. Conclusions: Sustained simulated weightlessness (42 days) significantly exacerbated retina-related damage, with both reduced macular blood supply and increased FAZ density suggesting the development of retinal ischemic changes, which disrupt visual electrophysiology. Retinal damage in human astronauts under long-term outer space conditions may be prevented by intervening in ischemic changes in the retina during the early stages of weightlessness.

Late-Onset Panuveitis in a Chinese Girl with Sporadic Blau Syndrome: A Case Report.

Introduction: Blau syndrome (BS) is a rare autoimmune disease. We report here an atypical case of BS. Case Presentation: We present a case of late-onset eye manifestations in a Chinese girl of 18 years old with sporadic BS, presenting with panuveitis. We performed comprehensive ocular examinations including fluorescein fundus angiography and indocyanine green angiography for her. The oral hormone plus local anti-inflammatory eye drops have well controlled the inflammation of her eyes. Conclusion: Our case highlights the necessity of systemic medical history inquiry for every eye discomfort.

Randomized controlled trial on the efficacy and safety of autologous serum eye drops in dry eye syndrome.

BACKGROUND: Autologous serum eye drops (ASEDs), a novel treatment derived from blood serum, have emerged as a groundbreaking solution for managing dry eye syndrome (DES). These drops have shown significant promise in relieving the distressing symptoms of DES. This study aimed to evaluate the safety and effectiveness of ASEDs compared to traditional treatments, which often prove inadequate or result in unwanted side effects, particularly in individuals with moderate-to-severe DES. AIM: To evaluate whether ASEDs are safer and more effective than conventional artificial tears in the treatment of moderate-to-severe DES. METHODS: This multi-centered randomized controlled trial included 240 patients with moderate-to-severe DES from three ophthalmology clinics in China. They were randomly assigned to receive either ASEDs or artificial tears for 12 wk. The primary outcome was the change in the ocular surface disease index (OSDI) score, with secondary outcomes including tear break-up time (TBUT), Schirmer I test, corneal fluorescein staining (CFS), and conjunctival impression cytology (CIC). Statistics analysis was performed using an analysis of covariance with adjustments made for baseline values. RESULTS: Our findings revealed that both ASEDs and artificial tears significantly improved the OSDI score, TBUT, Schirmer I test, CFS, and CIC from baseline to week 12. The ASEDs group showed significantly greater improvement in all these measures than the artificial tears group (all P values < 0.05). The average difference in the OSDI score between the two cohorts was -10.3 (95% confidence interval: -13.6 to -7.0), indicating a substantial improvement in the ASEDs group. The occurrence of adverse events was comparable between cohorts, with no reports of severe adverse events. CONCLUSION: ASEDs are more effective and safer than artificial tears for mitigating symptoms of moderate-to-severe DES. ASEDs could be an alternative/supplementary therapy for patients with DES less responsive to traditional treatments.

Hemorrhagic retinal arterial macroaneurysm combined with branch retinal artery occlusion treated with intravitreal conbercept injection: A case report.

RATIONALE: Branch retinal artery occlusion (BRAO) is a rare complication of retinal arterial macroaneurysm (RAM), a low-incidence ocular disease. PATIENT CONCERNS: A 75-year-old woman presented with a chief complaint of blurred vision. DIAGNOSES: The patient for 4 days received a diagnosis of RAM combined with BRAO. INTERVENTIONS: The patient was treated with two successive intravitreal conbercept injections. OUTCOMES: The patient's best-corrected visual acuity improved, and the RAM diminished. LESSONS: Administration of conbercept injection might be an effective treatment for complex RAM with BRAO.

Incidence of wound dehiscence after keratoplasty: a meta-analysis of observational studies.

Background: The comprehensive investigation of the association between keratoplasty and wound dehiscence remains limited, despite corneal disease being a leading cause of visual impairment. Methods: A meticulous search strategy was executed across prominent databases such as Web of Science, PubMed, Cochrane Library, and Embase. Data relevant to our research objective were extracted from eligible studies. The methodological quality of each study was assessed using the ROBINS-I tool, while statistical analysis was conducted utilizing STATA 17.0. To evaluate potential publication bias, the Funnel plot and Egger's test were employed. Results: A total of 11 articles were deemed suitable for inclusion in our analysis. Our findings indicate that the overall incidence of wound dehiscence following keratoplasty was estimated to be 1.9% (95% CI: 0.013, 0.026), although substantial heterogeneity was observed (I2 = 72.798%). Notably, developed countries exhibited a higher incidence of wound dehiscence compared to their developing counterparts. Furthermore, the occurrence of wound dehiscence was found to be lower in deep anterior lamellar keratoplasty (DALK) procedures when compared to penetrating keratoplasty (PK). Analysis utilizing Egger's linear regression method yielded no evidence of publication bias (p = 0.91). Moreover, within the first year post-keratoplasty, approximately 31.4% of patients experienced wound dehiscence (95% CI: 0.149, 0.503), and 43.1% exhibited a decline in best-corrected visual acuity (BCVA) (95% CI, 0.341, 0.522). Conclusion: The results of our study unveiled the occurrence rate of wound dehiscence following keratoplasty, exhibiting variations based on economic level and the specific surgical procedure employed. Furthermore, onset time of wound dehiscence and visual acuity warrant consideration.

KLF5/MDM2 Axis Modulates Oxidative Stress and Epithelial-Mesenchymal Transition in Human Lens Epithelial Cells: The Role in Diabetic Cataract.

Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The expression patterns of KLF5 were detected in vivo and in vitro. Then, KLF5 was knocked down in human lens epithelial cells (HLECs) to explore its functional roles and underlying mechanisms. Dual-luciferase reporter assay and chromatin immunoprecipitation analysis were used to detect whether KLF5 could bind the promoter of E3 ubiquitin ligase mouse double minute 2 (MDM2), a key regulator of EMT. Lastly, the regulation of KLF5 in the biological behaviors of HLECs via MDM2 was analyzed. We found a significant increase of KLF5 in the DC lens anterior capsular, diabetic rat lens, and high glucose (HG)-stimulated HLECs. Knockdown of KLF5 inhibited oxidative stress, inflammation, migration, and EMT of HG-stimulated HLECs. KLF5 silencing impeded MDM2 expression and restricted the activation of MARK1/FAK and NF-κB signaling pathways in HLECs under HG condition. Additionally, KLF5 was found to bind the MDM2 promoter and enhance the transcriptional activity of MDM2. The protective effects by silencing KLF5 on HG-cultured HLECs could be offset by MDM2 overexpression. We demonstrated that knockdown of KLF5 alleviated oxidative stress, migration, and EMT of HG-cultured HLECs by regulating MDM2, suggesting a potential therapeutic strategy for DC.

PDLIM1 inhibits cell migration and invasion in diabetic retinopathy via negatively regulating Wnt3a.

The injury of vascular endothelial cells is a crucial factor in the development of diabetic retinopathy (DR). PDLIM1 (a member of the PDZ and LIM protein family) has been reported to exert an essential function in vascular diseases. This study aimed to elucidate the role of PDLIM1 on retinal vascular endothelial cells in DR. Immunofluorescence staining was used to localize the expression of PDLIM1 in the mouse retina. In some tumor diseases, PDLIM1 has been reported to play a key role in regulating the Wnt pathway. However, no in-depth reports have been found in DR. Retinal capillary endothelial cells (RCECs) were treated with high-glucose and high-lipid (HG/HL) culture medium, and siRNA transfection to investigate the role of PDLIM1 in DR. PDLIM1 and Wnt3a expression was confirmed by qRT-PCR and western blotting. Flow cytometry, Transwell assay, and scratch assay were used to test the ability of cell apoptosis, migration, and invasion. PDLIM1 was mainly expressed in the retinal pigment epithelium (RPE), ganglion cell layer (GCL), inner plexus layer (IPL), and outer plexus layer (OPL). HG/HL increased Wnt3a levels and promoted cell's ability of apoptosis, migration, and invasion, which were reversed by the knockdown of PDLIM1. PDLIM1 was found to play a protective role in diabetic retinopathy by counter-regulating Wnt3a. PDLIM1 ameliorates cell apoptosis, migration, and invasion by negatively regulating Wnt3a in RCECs of DR, which suggests that PDLIM1 might be a promising therapeutic target for DR treatment.

Full-Thickness Macular Hole After Intravitreal Conbercept Injection in Branch Retinal Vein Occlusion.

This article reports a case of macular hole (MH) formation following intravitreal conbercept injection for branch retinal vein occlusion (BRVO). A 70-year-old male received three consecutive intravitreal injections of conbercept for the treatment of macular edema secondary to BRVO in his left eye. Due to the outbreak of the COVID-19 epidemic, the patient was lost to follow-up. At two months follow-up, a full-thickness MH was detected by fundoscopic and optical coherence tomography examination. Fortunately, the MH was successfully closed after pars plana vitrectomy. MH is a rare complication following intravitreal injections for RVO, which should be considered by clinicians.

Analysis and modeling of myopia-related factors based on questionnaire survey.

With the rapid development of science and technology, the trend of low age myopia is becoming increasingly significant. The latest national survey done by the Chinese government found that more than 80% of Chinese teenagers suffer from myopia. Adolescent myopia is closely related to living environment, heredity, and living habits. Quantifying the relationship between myopia and living environment, heredity, and living habits is conductive to the prevention and intervention of adolescent myopia. In this study, we investigated the relationships between four main factors (environment, habits, parental vision, and demographic) and myopia status by analyzing the questionnaire data. Data were collected from Chengdu, China in 2021, including 2808 myopia samples and 5693 non-myopia samples, with a total of 22 features. Then, these 22 features were inputted into three machine learning algorithms to discriminate the two classes of samples. Results show that the computational model could produce an AUC of 0.768. To pick out the most important features which play important roles in classification, we used incremental feature selection strategy to screen the 22 features. As a result, we found that the 4 most influential features with XGBoost could achieve a competitive AUC of 0.764. To further investigate the risk and protective factors affecting adolescent myopia, we used OR values derived from MLE-LR to analyze the relationship between 22 features and adolescent myopia. Results showed that the age variable was the most significant risk factor for myopia, followed by the myopia status of parents. The most protective factor for eyesight is the measure taken by the children, followed by the distance between books and eyes when reading. These discoveries can guide the prevention and control of myopia in children and adolescents.

Therapeutic potential of pupilloplasty combined with phacomulsification and intraocular lens implantation against uveitis-induced cataract.

AIM: To evaluate the therapeutic effect of pupilloplasty combined with phacomulsification and intraocular lens implantation (PPI) in uveitis-induced cataract. METHODS: Total 28 patients with uveitis-induced cataract were enrolled. Within 3mo before the PPI, 7 cases accompanied with glaucoma maintained carteolol hydrochloride for lowering intraocular pressure, and 1 case maintained glucocorticoid for anti-inflammation. The baseline characteristics, treatment processes, and outcomes of enrolled cases were retrospectively analyzed. Hematoxylin and eosin (HE) staining was performed to reveal the histopathological changes of iris tissues. RESULTS: Iris hemorrhage was the only intraoperative complication observed in 2 cases. After the surgery, normal intraocular pressure, right position of intraocular lens, and improved visual gain [best corrected visual acuity (BCVA)>0.5] were achieved. Postoperative keratic precipitates was observed in 2 cases, which was recovered within 1wk. During the follow-up of 5-10y, no recurrence of uveitis was found in 27 cases (96.43%). Uveitis only recurred in one case with the onset of ankylosing spondylitis. HE staining showed iris stroma (all samples), pigment cell hyperplasia in pigment epithelium (n=9) and stroma (n=19), inflammatory cell infiltration in iris (n=7), and neovascularization in iris surface (n=2). CONCLUSION: PPI improves the visual gain and prevents the long-term recurrence of uveitis in patients with uveitis-induced cataract, including those with preoperative intraocular pressure abnormality (glaucoma) and inflammation (active uveitis). Uveitis presents stroma atrophy, pigment cell hyperplasia, and inflammatory cell infiltration, even in a quiet state.

Force-Induced Synergetic Pigmentary and Structural Color Change of Liquid Crystalline Elastomer with Nanoparticle-Enhanced Mechanosensitivity.

The ability of some animals to rapidly change their colors can greatly improve their chances of escaping predators or hunting prey. A classic example is cephalopods, which can rapidly shift through a wide range of colors. This ability is based on the synergetic effect of the change of pigmentary and structural colors exhibited by their own two categories of color-changing cells: supernatant chromatophores offer various pigmentary colors and lower iridophores or leucophores reflect the different structural colors by adjusting their periodicities. Here, a mechanochromic liquid crystalline elastomer with force-induced synergetic pigmentary and structural color change, whose mechanosensitivity is enhanced by the stress-concentration induced by the doped nanoparticle, is presented. The materials have a large color-changing gamut and high mechanochromic sensitivity, which exhibit great potential in the field of mechanical detectors, sensors, and anti-counterfeiting materials.

Structural damage to the rat eye following long-term simulated weightlessness.

To better perform space missions and develop human spaceflights, the eye health of astronauts is receiving increasing attention from researchers. In this study, we used prolonged tail suspension to simulate microgravity cephalad fluid shift in space to observe intraocular pressure (IOP) changes, retinal structure, and optic nerve damage in rats. We observed significant choroidal thickening and optic nerve demyelination lesions in the rats in each experimental group. At the cellular level, retinal ganglion cells (RGCs) survival was significantly reduced, optic nerve oligodendrocytes were reduced, and apoptotic factors and microglia-mediated inflammation-related factors were detected in both the retina and optic nerve. The severity of these changes increased with increasing tails suspension time. In conclusion, simulated long-term microgravity can lead to slight intraocular pressure fluctuations, choroidal thickening, reduced RGCs survival, and optic nerve demyelination in rats.

A rare case of congenital pupillary abnormality: a case report.

BACKGROUND: Congenital anomalies of the pupil are quite varied, including abnormal size, shape, color, response to stimulus, and function. We are here reporting an unusual case presented with the absence of pupillary opening with folds of iris tissue at the center. Only an extremely small pupil (diameter < 0.5 mm) could be observed during the operation. CASE PRESENTATION: A 15-year-old male patient visited our outpatient clinic due to vision difficulty in his right eye for more than ten years. The best-corrected visual acuity was 2.0 logMAR and 0 logMAR for the right and left eye, respectively. There were amblyopia, astigmatism and constant exotropia in his right eye. Ophthalmic examination of the right eye showed flat iris root, minimal iris pigmentation, and the pupil area was entirely covered by iris tissue. Lens status and fundus evaluation could not be commented. The left eye was found to be within normal limit. Based on ophthalmic examination, the admission diagnosis was given as acorea. Pupilloplasty was performed on the right eye due to the situation that the iris tissue blocked the visual axis, which led to visual impairment and stimulus deprivation amblyopia. However, an extremely small pupil at the center of his pupillary area was observed during the operation. The postoperative course was favorable, and a normal pupil was secured. Hospital discharge diagnosis was given as microcoria, and amblyopia treatment was followed. CONCLUSIONS: We report a rare case of congenital pupillary abnormality. The further diagnosis was given as microcoria, which should be differentiated from acorea. For this kind of pupil disorder which blocks the visual axis, early diagnosis and treatment can help prevent the development of stimulus deprivation amblyopia.

Spaceflight-associated neuro-ocular syndrome: a review of potential pathogenesis and intervention.

With the continuing progress in space exploration, a new and perplexing condition related to spaceflight ocular syndrome has emerged in the past four decades. National Aeronautics and Space Administration (NASA) has named this condition "spaceflight-associated neuro-ocular syndrome" (SANS). This article gives an overview of the current research about SANS and traditional Chinese medicine (TCM) by analyzing the existing publications on PubMed and CNKI and reports from NASA about SANS, summarizing the potential pathogenesis of SANS and physical interventions for treating SANS, and discussing the feasibility of treating SANS with TCM. Due to the unique characteristics of the space environment, it is infeasible to conduct large-scale human studies of SANS. SANS may be the result of the interaction of multiple factors, including inflammation and fluid displacement in the optic nerve sheath and cerebrospinal fluid. We should pay attention to SANS. Visual function is not only related to the health of astronauts but also closely related to space operations. TCM has antioxidative stress and antiapoptotic effects and is widely used for optic nerve diseases. TCM has great potential to prevent SANS.

Remotely Controlling Drug Release by Light-Responsive Cholesteric Liquid Crystal Microcapsules Triggered by Molecular Motors.

Stimuli-responsive smart nanocarriers are an emerging class of materials applicable in fields including drug delivery and tissue engineering. Instead of constructing responsive polymer shells to control the release and delivery of drugs, in this work, we put forward a novel strategy to endow the internal drugs with light responsivity. The microcapsule consisted of molecular motor (MM)-doped cholesteric liquid crystals (CLCs) and drugs. The drug in gelatin-gum arabic microcapsules can protect the carried drugs for a long time with a low release speed totally resulting from drug diffusion. Under UV light, the MM isomerizes and the chirality changes, inducing the alteration of the superstructure of the CLCs. In this process, the cooperative molecular disturbance accelerates the diffusion of the drugs from the microcapsule core to the outside. As a result, thanks to the cooperative effect of liquid crystalline mesogens, molecular-scale geometric changes of motors could be amplified to the microscale disturbance of the self-organized superstructure of the CLCs, resulting in the acceleration of the drug release. This method is hoped to provide opportunities in the design and fabrication of novel functional drug delivery systems.

Novel Likely Pathogenic Variants Identified by Panel-Based Exome Sequencing in Congenital Cataract Patients.

PURPOSE: To identify likely pathogenic variants in three families with congenital cataracts via panel-based exome sequencing. METHODS: A panel containing 153 genes associated with congenital cataracts was designed. Genes were selected through reference to databases including the Human Gene Mutation Database (HGMD), Online Mendelian Inheritance in Man (OMIM), Genetic Home Reference, and the latest peer-reviewed publications on the genetics of hereditary cataracts. Panel-based exome sequencing was performed with the Illumina HiSeq X-Ten platform, and then the identified variants were confirmed with Sanger sequencing and evaluated according to the American College of Medical Genetics and Genomics (ACMG) criteria. RESULTS: Three likely pathogenic variants were found. A novel CRYBB2: c.230G > T p.G77V variant was identified in family A, a novel CRYBB2: c.230G > A p.G77D variant was identified in family B, and a novel CRYGD: c.475delG p.A159Pfs∗9 variant was identified in family C. CONCLUSION: Panel-based exome sequencing revealed three likely pathogenic variants in three unrelated Chinese families with congenital cataracts. These data expand the genetic spectrum associated with congenital cataracts.

Integrating network pharmacological and experimental models to investigate the therapeutic effects of baicalein in glaucoma.

BACKGROUND: Traditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism. METHODS: Network pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation. RESULTS: The results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma. CONCLUSION: By combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis.

Whole-exome sequencing identification of a recurrent CRYBB2 variant in a four-generation Chinese family with congenital nuclear cataracts.

Congenital cataracts is the most common cause of visual impairment and blindness in children. Although there have been extensive studies into the pathogenesis of congenital cataracts, the pathogenic mechanism underlying the recurrent variant CRYBB2:c.62T>A(p.I21N) has not been previously reported. Thus, the present study aimed to use whole-exome sequencing (WES) to identify potential genetic variants and investigate how they may have induced the occurrence of cataracts in a four-generation Chinese family with congenital nuclear cataracts. The medical history of this family was recorded and WES was conducted for one proband. Sanger sequencing was used to verify the presence of the putative variant in all participants. PolyPhen-2, SIFT and ProtScale were used to analyze the effect of the identified variants on protein function and hydrophobicity, and Pymol was used to show the structure of the wild-type (Wt) and mutant ß-crystallin B2 (CRYBB2) protein. Full-length Wt-CRYBB2 or mutant-CRYBB2 (I21N-CRYBB2) were fused to green fluorescent protein (GFP), and the recombinant plasmids were transfected into HeLa cells. Reverse transcription-quantitative PCR and western blotting were used to detect the expression levels of CRYBB2 mRNA and protein. Immunofluorescence and flow cytometry analyses were used to detect protein localization and apoptosis, respectively. A recurrent variant CRYBB2:c.62T>A(p.I21N) was identified in a four-generation Chinese family with congenital nuclear cataracts. Multiple-sequence alignment of CRYBB2 demonstrated that codon 21 was highly conserved. Pymol revealed that the structure of the I21N-CRYBB2 protein was distinct from that of Wt-CRYBB2. PolyPhen-2 predicted that it had a variant provean score 1.0, suggesting it was 'probably damaging', and SIFT predicted it had a variant provean score of -5.113, indicating it was 'deleterious'. ProtScale indicated that the hydrophobicity of the mutation site was significantly reduced. The protein expression levels of the I21N-CRYBB2 were decreased compared with the Wt-CRYBB2. Immunofluorescence analysis revealed that the variant I21N-CRYBB2 protein tended to accumulate around the nucleus, and flow cytometry analysis indicated that it increased cell apoptosis. Furthermore, I21N-CRYBB2 induced the activation of the unfolded protein response (UPR). In conclusion, a pathogenic variant of CRYBB2:c.62T>A(p.I21N) was identified via WES in a four-generation Chinese family with congenital nuclear cataracts. Through biological analysis, it was found that the variant induced abnormal protein aggregation, activated the UPR and triggered excessive cell apoptosis, which may lead to the occurrence of congenital nuclear cataracts in this family.

Whole-exome sequencing identifies an RS1 variant in a Chinese family with X-linked retinoschisis.

A notable behavioural feature of X-linked retinoschisis (XLRS) is extensive structural schisis (splitting) of the outer plexiform and inner nuclear layers of the neurosensory retina, which is partly combined with complications related to vitreous hemorrhage, macular holes and retinal detachment. The present study aimed to identify the pathogenic gene mutation in a three-generation Chinese family with XLRS by whole-exome sequencing (WES). The clinical information of a three-generation Chinese family with cases of XLRS was collected. WES was performed for the proband. A comparison with the human reference genome sequence (hg38) and bioinformatic analysis were performed to reveal putative variants and Sanger sequencing was applied to verify mutations in this family and healthy control participants. Intraretinal cystic spaces were detected by optical coherence tomography imaging. Structures of the wild-type and mutant retinoschisin 1 (RS1) protein were modelled by PyMol. Almost all patients had a history of vision loss and abnormal blue-purple colour vision; however, the phenotypes of the 4 patients were distinctly different. There was no linear correlation between phenotypic severity and age. A recurrent RS1 (Xp22.2) mutation (NM_000330: c.559C>T) was detected, resulting in the p.Q187X variant. According to the protein model, this variant is likely pathogenic. The present study was the first to report that RS1:c.559C>T induces XLRS in a three-generation Chinese pedigree, with the mutation leading to premature termination of translation of the RS1 protein. WES was able to diagnose XLRS, which has the characteristics of clinical and genetic heterogeneity.