Non-typical persistent hyperplastic primary vitreous: a rare case report and review of the literature.

BACKGROUND: Persistent hyperplastic primary vitreous (PHPV), also known as persistent fetal vasculature (PFV), is a clinical entity that traditionally presents with leukocoria, microphthalmia, retinal dysplasia, or eyeball shrinkage which is associated with poor vision. However, there is a dearth of literature on cases of PHPV in adulthood or with asymptomatic occurrence. This report presents the clinical and pathological findings of a non-typical PHPV case and discuss the current knowledge for this condition. CASE PRESENTATION: A 68-year-old healthy male was referred to our outpatient department for evaluation of age-related cataract without other visual symptoms. Preoperative fundus examination occasionally detected an isolated stalk-like band extending to the posterior pole of the eye with normal central vitreous and retina. Other ocular examinations including b-mode ultrasonography, optical coherence tomography did not unveil any abnormalities, which caused diagnostic uncertainty. We referred to cataract surgery along with histopathological study, that revealed characteristics of PHPV including fibrous connective tissues mainly composed of fibrocyte proliferation and a very few capillary vessels. Thereafter, a definitive diagnosis of non-typical PHPV was established. CONCLUSION: Our case is unique due to it was not discovered until adulthood, presence with only age-related cataract, and accompanied with normal central vitreous and retina. Histopathological explorations lead to an accurate diagnosis of the condition. Those results broaden the phenotype spectrums of PHPV and further provide clinical clues for the cognition of the disease.

Investigation of the Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 in Diabetic Retinopathy.

PURPOSE: Diabetic retinopathy (DR) has become a major cause of blindness with increased prevalence of diabetic mellitus. Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) plays a part in pathological neovascularization. This study aimed to investigate the role of CEACAM1 in the progression of DR. METHODS: Aqueous and vitreous samples were collected from proliferative or non-proliferative DR and the control group. Multiplex fluorescent bead-based immunoassays were used to detect the levels of Cytokines. Expression of CEACAM1, VEGF, VEGF receptor 2 (VEGFR2) and hypoxia-induced factor-1α (HIF-1α) were detected in human retinal microvascular endothelial cells (HRECs). RESULTS: CEACAM1 and VEGF levels were significantly upregulated in PDR group and positively correlated with PDR progression. Expression CEACAM1 and VEGFR2 were increased in HRECs under hypoxic conditions. The HIF-1α/VEGFA/VEGFR2 pathway was blocked by CEACAM1 siRNA in vitro. CONCLUSIONS: CEACAM1 might play a role in the pathology of PDR. CEACAM1 might be a therapeutic target for retinal neovasculariztion.

Thioredoxin-1 regulates the autophagy induced by oxidative stress through LC3-II in human lens epithelial cells.

Oxidative stress plays a major role in age-related cataract development. The cellular antioxidant protein thioredoxin-1 (Trx-1) and its negative regulator, thioredoxin binding protein-2 (TBP-2), are pivotal in the cellular redox balance during oxidative stress. The aim of this study is to investigate the effect of Trx-1 and TBP-2 on LC3 I/LC3 II in oxidative stress-induced autophagy in human lens epithelial cells (LECs). In our study, LECs were treated with 50 µM H2 O2 for different durations, and the expression of Trx-1 and TBP-2 were measured by RT-PCR and Western blot. Trx-1 activity was evaluated by the thioredoxin activity fluorescent assay. The subcellular localization of Trx-1 and TBP-2 was evaluated by cellular immunofluorescence. The interaction between Trx-1 and TBP-2 was examined by co-immunoprecipitation. The cell viability was detected using CCK-8, and the expression of LC3-II/LC3-I was detected to evaluate the autophagy. The results showed that the mRNA levels of the Trx-1 and TBP-2 were kinetically changed after treatment with H2 O2 for different durations. Exposure to H2 O2 increased the expression of TBP-2 but not Trx-1, while the exposure inhibited Trx-1 activity. TBP-2 was co-localized with Trx-1, and exposure to H2 O2 increased the interaction between TBP-2 and Trx-1. Trx-1 overexpression enhanced the autophagic response under normal circumstances and it might regulate autophagy in the initial phase. This study demonstrates the differential role of Trx-1 in cellular oxidative stress response, oxidative stress increased Trx-1 interaction with TBP-2, and Trx-1/TBP-2 regulated the autophagic response in the initial phase through LC3-II.

Noncoding RNAs in cataract formation: Star molecules emerge in an endless stream.

For decades, research on the pathological mechanism of cataracts has usually focused on the abnormal protein changes caused by a series of risk factors. However, an entire class of molecules, termed non-coding RNA (ncRNA), was discovered in recent years and proven to be heavily involved in cataract formation. Recent studies have recognized the key regulatory roles of ncRNAs in cataracts by shaping cellular activities such as proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT). This review summarizes our current insight into the biogenesis, properties and functions of ncRNAs and then discusses the development of research on ncRNAs in cataracts. Considering the significant role of ncRNA in cataract formation, research on novel associated regulatory mechanisms is urgently needed, and the development of therapeutic alternatives for the treatment of cataracts seems promising.

Research Progress Concerning a Novel Intraocular Lens for the Prevention of Posterior Capsular Opacification.

Posterior capsular opacification (PCO) is the most common complication resulting from cataract surgery and limits the long-term postoperative visual outcome. Using Nd:YAG laser-assisted posterior capsulotomy for the clinical treatment of symptomatic PCO increases the risks of complications, such as glaucoma, retinal diseases, uveitis, and intraocular lens (IOL) pitting. Therefore, finding how to prevent PCO development is the subject of active investigations. As a replacement organ, the IOL is implanted into the lens capsule after cataract surgery, but it is also associated with the occurrence of PCO. Using IOL as a medium for PCO prophylaxis is a more facile and efficient method that has demonstrated various clinical application prospects. Thus, scientists have conducted a lot of research on new intraocular lens fabrication methods, such as optimizing IOL materials and design, and IOL surface modification (including plasma/ultraviolet/ozone treatment, chemical grafting, drug loading, coating modification, and layer-by-layer self-assembly methods). This paper summarizes the research progress for different types of intraocular lenses prepared by different surface modifications, including anti-biofouling IOLs, enhanced-adhesion IOLs, micro-patterned IOLs, photothermal IOLs, photodynamic IOLs, and drug-loading IOLs. These modified intraocular lenses inhibit PCO development by reducing the residual intraoperative lens epithelial cells or by regulating the cellular behavior of lens epithelial cells. In the future, more works are needed to improve the biosecurity and therapeutic efficacy of these modified IOLs.

CircRNA Is a Rising Star in Researches of Ocular Diseases.

A newly rediscovered subclass of noncoding RNAs, circular RNAs (circRNAs), is produced by a back-splicing mechanism with a covalently closed loop structure. They not only serve as the sponge for microRNAs (miRNAs) and proteins but also regulate gene expression and epigenetic modification, translate into peptides, and generate pseudogenes. Dysregulation of circRNA expression has opened a new chapter in the etiology of various human disorders, including cancer and cardiovascular, neurodegenerative, and ocular diseases. Recent studies recognized the vital roles that circRNAs played in the pathogenesis of various eye diseases, highlighting circRNAs as promising biomarkers for diagnosis and assessment of progression and prognosis. Interventions targeting circRNAs provide insights for developing novel treatments for these ocular diseases. This review summarizes our current perception of the properties, biogenesis, and functions of circRNAs and the development of circRNA researches related to ophthalmologic diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, glaucoma, corneal neovascularization, cataract, pterygium, proliferative vitreoretinopathy, retinoblastoma, and ocular melanoma.

Less mechanical loading attenuates osteoarthritis by reducing cartilage degeneration, subchondral bone remodelling, secondary inflammation, and activation of NLRP3 inflammasome.

AIMS: Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. METHODS: A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our radiographs showed that joint space was significantly enlarged in rats with less mechanical loading. Moreover, cartilage destruction was attenuated in the less mechanical loading group with lower histological damage scores, and lower expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13. In addition, subchondral bone abnormal changes were ameliorated in OA rats with less mechanical loading, as reduced bone mineral density (BMD), bone volume/tissue volume (BV/TV), and number of osteophytes and osteoclasts in the subchondral bone were observed. Finally, the level of serum inflammatory cytokines was significantly downregulated in the less mechanical loading group compared with the normal mechanical loading group, as well as the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), caspase-1, and interleukin 1ß (IL-1ß) in the cartilage. CONCLUSION: Less mechanical loading alleviates cartilage destruction, subchondral bone changes, and secondary inflammation in OA joints. This study provides fundamental insights into the benefit of non-weight loading rest for patients with OA. Cite this article: Bone Joint Res 2020;9(10):731-741.

Bromfenac Inhibits TGF-ß1-Induced Fibrotic Effects in Human Pterygium and Conjunctival Fibroblasts.

Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown antifibrotic effects on several diseases. The aims of the present in vitro study were to investigate the antifibrotic effects of bromfenac (a kind of NSAID) on primary human pterygium fibroblasts (HPFs) and primary human conjunctival fibroblasts (HConFs), as well as to explore the possible mechanisms of these effects. Methods: The cells used in this study were primary HPFs and HConFs, and profibrotic activation was induced by transforming growth factor-beta1 (TGF-ß1). Western blot, quantitative real-time PCR, and immunofluorescence (IF) assays were used to detect the effects of TGF-ß1 and bromfenac on the synthesis of fibronectin (FN), type III collagen (COL3), and alpha-smooth muscle actin (α-SMA) in HPFs and HConFs; the changes of signaling pathways were detected by Western blot; cell migration ability was detected by wound healing assay; cell proliferation ability was detected by CCK-8 assay; and pharmaceutical inhibitions of the downstream signaling pathways of TGF-ß1 were used to assess their possible associations with the effects of bromfenac. Results: Bromfenac suppressed the TGF-ß1-induced protein expression of FN (0.59 ± 0.07 folds, P = 0.008), COL3 (0.48 ± 0.08 folds, P = 0.001), and α-SMA (0.61 ± 0.03 folds, P = 0.008) in HPFs. Bromfenac also attenuated TGF-ß1-induced cell migration (0.30 ± 0.07 folds, P < 0.001), cell proliferation (0.64 ± 0.03 folds, P = 0.002) and the expression levels of p-AKT (0.66 ± 0.08 folds, P = 0.032), p-ERK1/2 (0.69 ± 0.11 folds, P = 0.003), and p-GSK-3ß-S9 (0.65 ± 0.10 folds, P = 0.002) in HPFs. PI3K/AKT inhibitor (wortmannin) and MEK/ERK inhibitor (U0126) reduced the TGF-ß1-induced synthesis of FN, COL3, and α-SMA in HPFs. All the results were similar in HConFs. Conclusions: Bromfenac protects against TGF-ß1-induced synthesis of FN, α-SMA, and COL3 in HPFs and HConFs at least in part by inactivating the AKT and ERK pathways.

The Function of Thioredoxin-Binding Protein-2 (TBP-2) in Different Diseases.

Thioredoxin-binding protein-2 (TBP-2) has an important role in the redox system, but it plays a different role in many different diseases (e.g., various cancers, diabetes mellitus (DM), cardiovascular disease, and cataracts) by influencing cell proliferation, differentiation, apoptosis, autophagy, and metabolism. Distinct transcription factors (TFs) stimulated by different factors combine with binding sites or proteins to upregulate or downregulate TBP-2 expression, in order to respond to the change in the internal environment. Most research disclosed that the main function of TBP-2 is associating with thioredoxin (Trx) to inhibit the antioxidant capacity of Trx. Furthermore, the TBP-2 located in tissues, whether normal or abnormal, has the ability to cause the dysfunctioning of cells and even death through different pathways, such as shortening the cell cycle and inducing apoptosis or autophagy. Through these studies, we found that TBP-2 promoted the development of diseases which are involved in inflammatory and oxidative damage. To a certain extent, we believe that there is some hidden connection between the biological functions which TBP-2 participates in and some distinct diseases. This review presents only a summary of the roles that TBP-2 plays in cancer, DM, cataracts, and so on, as well as its universal mechanisms. Further investigations are needed for the cell signaling pathways of the effects caused by TBP-2. A greater understanding of the mechanisms of TBP-2 could produce potential new targets for the treatment of diseases, including cancer and diabetes, cardiovascular disease, and cataracts.

An efficacy analysis of anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to multifocal choroiditis and comparison with wet age-related macular degeneration.

OBJECTIVE: To evaluate the effect of anti-vascular endothelial growth factor (VEGF) on juxtafoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis (MFC) and wet age-related macular degeneration (AMD). METHODS: In this retrospective, comparative study, 20 unique eyes with CNV were divided into two groups: 10 patients affected by MFC and 10 patients diagnosed with wet AMD. They all received local intravitreal (IVT) injections of ranibizumab, with 6 months of follow-up. Retreatment injections were performed based on findings suggestive of active neovascularization. RESULTS: Significant improvements were observed in the juxtafoveal CNV lesions, and average central macular thickness decreased in both groups following the anti-VEGF therapy (P<0.05). The average number of injections used in MFC patients was 1.6, while three injections on average were used in wet AMD patients (Z=-2.844, P=0.009). Best-corrected visual acuity was significantly improved in MFC patients after anti-VEGF therapy (P<0.05), and there was no significant difference in wet AMD patients between before anti-VEGF therapy and 6 months later (P>0.05). CONCLUSIONS: IVT ranibizumab resulted in good clinical outcomes for juxtafoveal CNV secondary to MFC and wet AMD, but the average number of injections used in MFC was fewer than that used in wet AMD over a 6-month observation period. Compared with the wet AMD group, visual acuity was obviously improved in the MFC group at 6 months.

Orbital sparganosis in an 8-year boy: a case report.

BACKGROUND: Sparganosis is one of the neglected but important food-borne parasitic zoonoses, with higher prevalence in Asian countries. The infection is commonly located in the subcutaneous tissue, brain, breast, and lung, but fewer reported infections involve the eye. Because the majority of patients with sparganosis are adults, it is likely to be missed in children. CASE PRESENTATION: An 8-year-old boy presented to our clinic complaining of a painless ocular mass in his right eye for 1 month. The boy had a history of eating frogs and frog poultice applications to his eyelids. The patient was checked for an elliptical mass near the medial wall of the right eye. Serodiagnosis testing was positive in an enzyme-linked immunosorbent assay. During surgical operation on the patient, calcified parasite eggs and foreign body granulomatous reaction were found using histological examination. Due to early detection and surgery, the patient fully recovered with no damage to his eyesight. CONCLUSIONS: Although rare, ocular sparganosis should be suspected in a mass of the eye when there is a history of eating frogs and frog poultice applications on eyelids. Early surgical resection is important for a good prognosis.

N-acetylcysteine treatment following spinal cord trauma reduces neural tissue damage and improves locomotor function in mice.

Following spinal cord trauma, mitochondrial dysfunction associated with increased oxidative stress is a critical event leading to leukocyte inflammatory responses, neuronal cell death and demyelination, contributing to permanent locomotor and neurological disability. The present study demonstrated that the mitochondrial enhancer N-acetylcysteine (NAC) may restore redox balance via enhancement of mitochondrial respiratory activity following traumatic spinal cord injury (SCI). In addition, NAC ameliorates oxidative stress-induced neuronal loss, demyelination, leukocyte infiltration and inflammatory mediator expression and improves long-term locomotor function. Furthermore, neuronal survival and neurological recovery are significantly correlated with increased mitochondrial bioenergetics in SCI following treatment with NAC. Therefore, NAC may represent a potential therapeutic agent for preserving mitochondrial dynamics and integrity following traumatic SCI.

Targeting endothelin receptors A and B attenuates the inflammatory response and improves locomotor function following spinal cord injury in mice.

After spinal cord injury (SCI), the disruption of blood-spinal cord barrier by activation of the endothelin (ET) system is a critical event leading to leukocyte infiltration, inflammatory response and oxidative stress, contributing to neurological disability. In the present study, we showed that blockade of ET receptor A (ETAR) and/or ET receptor B (ETBR) prevented early inflammatory responses directly via the inhibition of neutrophil and monocyte diapedesis and inflammatory mediator production following traumatic SCI in mice. Long-term neurological improvement, based on a series of tests of locomotor performance, occurred only in the spinal cord­injured mice following blockade of ETAR and ETBR. We also examined the post­traumatic changes of the micro-environment within the injured spinal cord of mice following blockade of ET receptors. Oxidative stress reflects an imbalance between malondialdehyde and superoxide dismutase in spinal cord­injured mice treated with vehicle, whereas blockade of ETAR and ETBR reversed the oxidation state imbalance. In addition, hemeoxygenase-1, a protective protease involved in early SCI, was increased in spinal cord­injured mice following the blockade of ETAR and ETBR, or only ETBR. Matrix metalloproteinase-9, a tissue-destructive protease involved in early damage, was decreased in the injured spinal cord of mice following blockade of ETAR, ETBR or a combination thereof. The findings of the present study therefore suggested an association between ETAR and ETBR in regulating early pathogenesis of SCI and determining the outcomes of long­term neurological recovery.