Impact of the preoperative cylinder on astigmatism correction in femtosecond lenticule extraction (FLEX): a prospective observational study.

PURPOSE: To explore the impact of the preoperative manifest cylinder on astigmatism correction via femtosecond lenticule extraction (FLEX), or small incision lenticule extraction (SMILE). METHODS: This was a prospective observational study. Eyes were categorized into mild (n = 88), moderate (n = 46), and severe (n = 53) astigmatism groups, based on the preoperative manifest cylinder. Vector analysis was conducted with the back vertex distance set at 12 mm. The primary outcome was the correction index (CI), with secondary outcomes including the safety, efficacy, predictability, and vectoral alterations related to FLEX. RESULTS: The average target-induced astigmatism was 0.45 ± 0.20 D, 0.95 ± 0.17 D, and 1.99 ± 0.65 D in the three groups (P < 0.001), and the average CI was 1.12± 0.05, 1.01 ± 0.03, and 0.95 ± 0.02 (P = 0.020), with the severe astigmatism group displaying a notably lower CI. The efficacy, safety, predictability, or stability of FLEX did not demonstrate any significant differences among the three groups. The CIs exhibited a significant difference in eyes with with-the-rule (WTR) astigmatism and against-the-rule (ATR) astigmatism from the mild to severe astigmatism group. In eyes with oblique astigmatism, the average CI exceeded one. CONCLUSION: Patients with manifest cylinder exceeding 1.25 D have a heightened risk of under-correction in WTR and ATR astigmatism compared to those with mild astigmatism, and mild over-correction may occur in cases of oblique astigmatism.

The effects of an electronic head-mounted display in vision rehabilitation for patients with tunnel vision.

PURPOSE: To investigate the effect of a new head-mounted electronic visual aid-Acesight on improving visual function and daily activities in patients with tunnel vision. METHODS: 57 patients with tunnel vision participated in this study. The visual field (VF), visual acuity (VA), search ability, time of finding people from the side (TFPS), walking ability, and the subjective feelings of patients with and without Acesight were measured. RESULTS: 15 (36%) patients thought Acesight was "helpful", 16 (28%) thought it was "a little help", and 26 (46%) believed that it was "not helpful." The proportion of people aged < 60 years found Acesight helpful was higher. When wearing Acesight, the average horizontal VF diameter (°) (35.54[8.72]) and vertical VF diameter (°) (26.63[5.38]) were larger than those without visual aids (20.61[9.22], 18.19[6.67]) (P all < 0.001). The average TFPS before and while wearing the Acesight was 1.77s(0.32) and 1.19s(0.29), respectively (t = 14.28, P < 0.001). The average search times, number of collisions, walking speeds when wearing the Acesight were not statistically different from those without visual aids (P all > 0.05). CONCLUSION: More than half of patients with tunnel vision found the Acesight helpful, and a higher proportion of those aged < 60 years old found it helpful. Acesight can expand the horizontal and vertical VF of patients with tunnel vision and can enable patients to detect objects coming from the side earlier. TRIAL REGISTRATION: ChiCTR2000028859; Date of registration: 2020/1/5; URL: http://www.chictr.org.cn/showproj.aspx?proj=47129.

The dynamic changes and influencing factors of visual symptoms after small incision lenticule extraction.

BACKGROUND: To investigate the dynamic changes and influencing factors of visual symptoms after small incision lenticule extraction (SMILE). METHODS: This was a prospective observational study. Visual symptoms including glare, haloes, starbursts, hazy vision, fluctuation, blurred vision, double vision and focusing difficulties were evaluated before and 1, 3, 6 months after SMILE using a questionnaire. Generalized linear mixed models were used to assess the effects of preoperative characteristics and objective visual quality parameters on postoperative visual symptoms. RESULTS: 73 patients/146 eyes were enrolled. Preoperatively, the most common symptoms were glare (55% of eyes), haloes (48%), starbursts (44%) and blurred vision (37%). At 1 month postoperatively, the incidence and extent scores of glare, haloes, hazy vision and fluctuation rose significantly. At 3 months, the incidence and extent scores of glare, haloes and hazy vision restored to baseline. And at 6 months, the extent scores of fluctuation returned to baseline. Other symptoms (e.g., starbursts) did not change before and 1, 3, 6 months after SMILE. Preoperative visual symptoms were associated with postoperative symptoms, as patients with a symptom preoperatively had higher postoperative scores for that symptom. Age was related to postoperative extent of double vision (coefficient = 0.12, P = 0.046). There were no significant associations between postoperative visual symptoms and preoperative SE, scotopic pupil size, angle kappa (with intraoperative adjustment), postoperative HOAs or scattering indexes. CONCLUSIONS: The incidence and extent scores of hazy vision, glare, haloes and fluctuation increased at the first month after SMILE, and recovered to baseline at 3 or 6 months. Preoperative visual symptoms were associated with the postoperative symptoms and should be fully considered before SMILE.

Retinal neurodegeneration in a mouse model of green-light-induced myopia.

PURPOSE: To determine the retinal neurodegeneration occurring in mice with green-light-induced myopia. METHODS: Four-week-old mice were raised under white or green light (peak at 510 nm). Refraction and axial length (AL) were measured before and after eight weeks of illumination treatment. TUNEL staining, electron microscopy and the Visual Cliff test were performed to identify the conditions of retinal degeneration. The distinct protein signatures of retina tissues were quantified by mass spectrometry (MS) - based proteomics, and analyzed by Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation and STRING database. Western blot was used to detect the expression of the specific protein. RESULTS: Green-light-induced myopia was developed in mice after eight weeks of illumination treatment. Apoptosis and the abnormality in ultrastructure and visual function of mice exposed to green light were found through morphological and behavioral experiment, indicating retinal degeneration. The altered proteome was associated with Human Phenotype Ontology (HPO) annotations sets of 'abnormality of visual evoked potentials' and 'neuronal loss in central nervous system'. KEGG annotation demonstrated the altered pathway of the dopaminergic synapse in the myopic mice. STRING database was utilized with an effort to identify the molecular pathways within, and dysregulation of mitochondrial metabolism was revealed. CONCLUSIONS: Overall, our study revealed molecular differences and pathways underlying retinal degeneration in the mouse model of green-light-induced myopia. These findings might provide insights into further research into myopia prevention and control.

Analysis of macular blood flow changes in thyroid associated ophthalmopathy.

BACKGROUND: To evaluate the changes in macular superficial retinal vessel density and their relation with visual acuity in thyroid-associated ophthalmopathy (TAO) patients with different severity. METHODS: This cross-sectional observational study included 70 TAO patients and 70 healthy controls. Only data from the right eyes were analyzed. TAO patients were divided into 7 subgroups according to the NOSPECS score. Foveal avascular zone (FAZ), vascular density (VD), and perfusion density (PD) of macular 1 mm diameter and 6 mm diameter areas were measured by optical coherence tomography angiography (OCTA). RESULTS: In TAO patients, significant increases were found in macular and foveal vascular densities (FVD) and perfusion densities (FPD) while a significant decrease was found in the FAZ area when compared with the control group (p < 0.05). Spearman correlation analysis and multiple linear regression analysis showed that TAO severity grade was negatively correlated with FVD (ß = -1.150, p = 0.032), FPD (ß = -0.024, p = 0.042), MVD (ß = -0.583, p = 0.020) and MPD (ß = -0.011, p = 0.010). Clinical activity score (CAS) score showed positive correlation with FVD (ß = 0.794, p = 0.035) and FPD(ß = 0.017, p = 0.041). FVD (ß = -0.009, p = 0.033), MVD(ß = -0.034, p < 0.001), FPD(ß = -0.416, p = 0.039) and MPD(ß = -2.428, p < 0.001) all showed negative correlation with best corrected visual acuity (BCVA). CONCLUSIONS: There was an overall increase in superficial macular blood flow in TAO patients compared with healthy controls and the blood flow decreased as TAO got worse. Superficial macular flow density was negatively correlated with BCVA.

Contribution of M-opsin-based color vision to refractive development in mice.

M-opsin, encoded by opn1mw gene, is involved in green-light perception of mice. The role of M-opsin in emmetropization of mice remains uncertain. To answer the above question, 4-week-old wild-type (WT) mice were exposed to white light or green light (460-600 nm, a peak at 510 nm) for 12 weeks. Refractive development was estimated biweekly. After treatment, retinal function was assessed using electroretinogram (ERG). Dopamine (DA) in the retina was evaluated by high-performance liquid chromatography, M-opsin and S-opsin protein levels by Western blot and ELISA, and mRNA expressions of opn1mw and opn1sw by RT-PCR. Effects of M-opsin were further verified in Opn1mw-/- and WT mice raised in white light for 4 weeks. Refractive development was examined at 4, 6, and 8 weeks after birth. The retinal structure was estimated through hematoxylin and eosin staining (H&E) and transmission electron microscopy (TEM). Retinal wholemounts from WT and Opn1mw-/- mice were co-immunolabeled with M-opsin and S-opsin, their distribution and quantity were then assayed by immunofluorescence staining (IF). Expression of S-opsin protein and opn1sw mRNA were determined by Western blot, ELISA, or RT-PCR. Retinal function and DA content were analyzed by ERG and liquid chromatography tandem-mass spectrometry (LC-MS/MS), respectively. Lastly, visual cliff test was used to evaluate the depth perception of the Opn1mw-/- mice. We found that green light-treated WT mice were more myopic with increased M-opsin expression and decreased DA content than white light-treated WT mice after 12-week illumination. No electrophysiologic abnormalities were recorded in mice exposed to green light compared to those exposed to white light. A more hyperopic shift was further observed in 8-week-old Opn1mw-/- mice in white light with lower DA level and weakened cone function than the WT mice under white light. Neither obvious structural disruption of the retina nor abnormal depth perception was found in Opn1mw-/- mice. Together, these results suggested that the M-opsin-based color vision participated in the refractive development of mice. Overexposure to green light caused myopia, but less perception of the middle-wavelength components in white light promoted hyperopia in mice. Furthermore, possible dopaminergic signaling pathway was suggested in myopia induced by green light.

Ophthalmic services in Shanghai 2017: a cataract-centric city-wide government survey.

BACKGROUND: Demand for eye care has increased in recent decades in China due to rapid socioeconomic development and demographic shift. Knowledge of output and productivity of ophthalmic services would allow policymakers to optimize resource allocation, and is therefore essential. This study sought to map the landscape of ophthalmic services available in Shanghai, China. METHODS: In 2018, a government-led survey was conducted of all 86 tertiary/secondary hospitals and five major private hospitals providing eye care in Shanghai in the form of electronic questionnaire, which encompassed ophthalmic services (outpatient and emergency room [ER] visit, inpatient admissions, and surgical volume) and service productivity in terms of annual outpatient and ER visits per doctor, inpatient admissions per bed, and surgical volume per doctor. Comparisons were made among different levels of hospitals with categorical variables tested by Chi-square analysis. RESULTS: The response rate was 85.7%. The Eye and Ear, Nose, and Throat (EENT) Hospital was the largest tertiary specialty hospital, and alone contributed to the highest 21.0% of annual ophthalmic outpatient and ER visits (visits per doctor: 5460), compared with other 26 tertiary hospitals, 46 secondary hospitals and five private hospitals (visits per doctor: 3683, 4651 and 1876). The annual inpatient admission was 20,103, 56,992, 14,090, and 52,047 for the EENT Hospital, all the other tertiary hospitals, secondary hospitals and five private hospitals, respectively. Turnover rates were highest for the EENT Hospital and private hospitals. The average surgical volume at the EENT Hospital was 72,666, exceeding that of private (15,874.8) and other tertiary hospitals (3366.7). The EENT Hospital and private hospitals performed 16,982 (14.2%) and 55,538 (46.6%) of all cataract surgeries. Proportions of both complicated cataractous cases and complicated cataract surgeries at the EENT Hospital was the highest, followed by other tertiary and secondary/private hospitals (P < 0.0001). CONCLUSIONS: In Shanghai, public providers dominate ophthalmic services especially for complicated cases, with almost one fifth of services provided by the EENT Hospital alone, while private sectors, though not large in number, still effectively help meet large proportions of eye care demand. Optimization of hierarchical medical system is warranted to improve the efficiency and standardization of ophthalmic services.

The assistance of electronic visual aids with perceptual learning for the improvement in visual acuity in visually impaired children.

PURPOSE: To investigate the effect of electronic visual aids (EVA) combined with perceptual learning (PL) for the improvement in visual acuity for moderate to severe visually impaired and blind children. METHODS: Twenty-eight 6- to 14-year-old visually impaired children (19 boys and 9 girls) were divided into two groups: PL under the assistance of EVA (Group A, 14 children) and simple PL without EVA (Group B, 14 children). The content of PL was to search the inversed "E" in the crowding strings and connected with lines, 30 minutes a day for 6 months. EVA can provide 5-10 times magnification on the 4.3-inch screen. Uncorrected distance visual acuity (UCVA), best-corrected visual acuity (BCVA), near visual acuity (NVA) and refractive error were evaluated before and 3 and 6 months after training. RESULTS: Baseline UCVA, BCVA or NVA was comparable between the two groups. Three months after training, UCVA, BCVA and NVA improved significantly in Group A (p < 0.05). At the end of training, UCVA and BCVA continued progressing in Group A compared to 3 months (p = 0.01, 0.02), but visual acuity did not show significant improvement in Group B during the same time, except that UCVA improved at the first follow-up. Refractive error had no significant change post-training in both groups. CONCLUSIONS: Visually impaired children can benefit more from the combination of PL with EVA than simple PL, and the improvement in visual acuity accompanied no significant myopic shift. It may provide a new method of treatment and rehabilitation in visually impaired children.

Comparison of the posterior corneal elevation and biomechanics after SMILE and LASEK for myopia: a short- and long-term observation.

PURPOSE: This study compares the posterior corneal elevation and corneal biomechanics after small incision lenticule extraction (SMILE) and laser-assisted subepithelial keratomileusis (LASEK) for myopia correction in a short- and long-term observation. METHODS: This prospective study included 32 patients in the SMILE group and 32 patients in the LASEK group. Corneal posterior central elevation (PCE), posterior mean elevation (PME), corneal back power (Kb), and anterior chamber depth (ACD) were evaluated with Pentacam, and intraocular pressure (IOP), corneal hysteresis (CH), and corneal resistance factor (CRF) were evaluated with the ORA at pre-operation and 3 months and 3 years post-operation. RESULTS: Three months post-operatively, CH, CRF, and IOP decreased significantly and central posterior surface shifted backward in both groups (p < 0.05). CH was lower in the LASEK group (p = 0.03) and change of CH and CRF per unit corneal tissue removed (ΔCH/ablation depth (AD) and ΔCRF/AD) was lower in SMILE than in LASEK (p = 0.01, 0.03). Three years post-operatively, the PME shifted more posteriorly in LASEK (p = 0.04), but was stable in SMILE (p = 0.06). Kb flattened and ACD was shallower in both groups (compared to preoperative data, p < 0.001). CH in the LASEK group increased and is comparable to that in the SMILE group at 3 years post-operative. CONCLUSION: Both SMILE and LASEK can change the posterior surface and corneal biomechanics. SMILE may have less influence on corneal biomechanics than LASEK at an early stage post-operative in terms of per unit corneal tissue removed, but the effect became comparable in a long-term observation.

Comparative study of wave-front aberration and corneal Asphericity after SMILE and LASEK for myopia: a short and long term study.

BACKGROUND: The study compares the wave-front aberration and corneal asphericity from multiple perspectives after Small Incision Lenticule Extraction and Laser-assisted Subepithelial Keratomileusis for mild to moderate myopia in a short and long time period. METHODS: This prospective and comparative study included 32 eyes in the SMILE group, with a mean spherical equivalent (SE) of - 4.1 ± 0.9D and 32 eyes in the LASEK group, with a mean SE of - 3.7 ± 1.0D. Visual acuity, refractive error, wave-front aberration, corneal Q value and corneal refractive power were analyzed pre-, 3 months and 3 years post-operatively. RESULTS: There was no significant difference in refractive error, wave-front aberration, corneal Q value and corneal refractive power before treatment. Three months postoperative, Q value within 6 mm (SMILE: 0.46 ± 0.27, LASEK: 0.63 ± 0.28, p = 0.02), the relative peripheral corneal power (5-8 mm: p < 0.05), change of higher order aberration (SMILE: 0.10 ± 0.16, LASEK: 0.24 ± 0.20, p = 0.004) and spherical aberration (SA, SMILE: -0.07 ± 0.30, LASEK: -0.41 ± 0.40, p < 0.001) were significantly lower in the SMILE than in LASEK group. The visual acuity, refractive error, coma, peripheral Q value, central corneal power had no significant difference between the two groups. Three years post-operation, the corneal power distribution results and SA were similar to that of 3-month, while the Q value had no significant difference between the two groups. CONCLUSION: In the early stage after SMILE, the HOAs was lower, the corneal refractive power from central to periphery was more uniform than after LASEK; and in the long-term run, SMILE still preceded LASEK in the corneal asphericity and aberration.

Proinflammatory status in the aqueous humor of high myopic cataract eyes.

High myopia has long been recognized as an inflammation-related disease, and high myopic eyes are thought to have a proinflammatory internal microenvironment, which might predispose to the occurrence of certain inflammation-related complications such as fibrotic capsular contraction syndrome after cataract surgery. Therefore, the purpose of this study was to detect inflammatory cytokines expressed in the aqueous humor (AH) of high myopic cataract (HMC) patients. The cytokines were screened using a RayBio Human Cytokine Antibody Array in AH samples from 15 age-related cataract (ARC) patients and 15 HMC patients. Those detected by the screening assays were verified using a Bio-Plex Suspension Array System in AH samples from 35 ARC patients and 45 HMC patients. The cytokine antibody array showed that the expression level of interleukin-1 receptor antagonist (IL-1ra) in the AH was higher in ARC than in HMC, whereas opposite trends were found for monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and presumably secreted (RANTES), IL-8, platelet-derived growth factor-BB, and IL-6 (all P < 0.05). In the verification assay using the suspension cytokine array, only the expression levels of IL-1ra and MCP-1 were significantly different between the ARC and HMC groups (P = 0.014 and 0.038, respectively); these results were confirmed by western blot assays. Our results demonstrated that the expression of IL-1ra was significantly lower and the expression of MCP-1 was significantly higher in the AH of HMC than in ARC, suggestive of a proinflammatory status in the anterior chamber of HMC eyes.

Baseline traits of patients presenting at a low vision clinic in Shanghai, China.

BACKGROUND: Low vision, along with cataract, trachoma, onchocerciasis, childhood blindness and refractive error, is one of the priorities in the global initiative, VISION 2020-The Right to Sight. The purpose of this study was to characterize the traits of patients presenting at a low vision clinic in China. METHODS: A retrospective study was conducted of the records of 299 patients who visited the Low Vision Clinic of Eye and ENT Hospital Affiliated to Fudan University from January 2009 to May 2014. Reviewed parameters included age, gender, education, occupation, cause of visual impairment and types of low vision aids (LVAs) dispensed. RESULTS: Of all the patients (193 male; aged from 3 to 96 years, with a mean of 29.74 ± 25.23 years), 43.48% experienced moderate visual impairment, 25.42% had severe visual impairment and 21.07% were blind. The four major causes of visual impairment were congenital cataract (14.38%), degenerative myopia (13.71%), juvenile macular degeneration (9.36%) and retinitis pigmentosa (9.36%). The most common causes of visual impairment were congenital cataract (22.67%) in 0-19-year-olds, retinitis pigmentosa (20.62%) in 20-59-year-olds, and age-related macular degeneration (36.54%) in the 60+ group. With the help of LVAs, a significant improvement of distance and/or near vision or visual field was observed in 243 patients, of whom 185 accepted LVAs and 58 patients refused due to high price, inconvenience, young age (≤ 6 y), clumsy appearance and ignorance. The most commonly dispensed LVAs were stand magnifiers (21.57%) followed by spectacle-type LVAs (19.21%). CONCLUSIONS: The majority of the patients in our low vision clinic were young, the main causes of visual impairment were congenital and hereditary diseases. Stand magnifiers were the most commonly dispensed LVAs. High price was the major reason for refusing LVAs.

[Blue light and eye health].

Blue light, with the wavelength between 400 nm and 500 nm, has caused public concern because of the injury to the retinal cells. Meanwhile, it is important in circadian rhythm regulation, scotopic vision and ocular growth. Is the blue light safe? Should it be eliminated from the daily life? Here we review the effect and safety of the blue light.

Upregulation of regulator of G-protein signaling 2 in the sclera of a form deprivation myopic animal model.

PURPOSE: Scleral remodeling is an important mechanism underlying the development of myopia. Atropine, an antagonist of G protein-coupled muscarinic receptors, is currently used as an off-label treatment for myopia. Regulator of G-protein signaling 2 (RGS2) functions as an intracellular selective inhibitor of muscarinic receptors. In this study we measured scleral RGS2 expression and scleral remodeling in an animal model of myopia in the presence or absence of atropine treatment. METHODS: GUINEA PIGS WERE ASSIGNED TO FOUR GROUPS: normal (free of form deprivation), form deprivation myopia (FDM) for 4 weeks, FDM treated with saline, and FDM treated with atropine. Biometric measurements were then performed. RGS2 expression levels and scleral remodeling, including scleral thickness and collagen type I expression, were compared among the four groups. RESULTS: Compared with normal eyes and contralateral control eyes, the FDM eyes had the most prominent changes in refraction, axial length, and scleral remodeling, indicating myopia. There was no significant difference between control and normal eyes. Hematoxylin and eosin staining showed that the scleral thickness was significantly thinner in the posterior pole region of FDM eyes compared to normal eyes. Real-time PCR and western blot analysis showed a significant decrease in posterior scleral collagen type I mRNA and protein expression in the FDM eyes compared to the normal eyes. The FDM eyes also had increased levels of RGS2 mRNA and protein expression in the sclera. Atropine treatment attenuated the FDM-induced changes in refraction, axial length, and scleral remodeling. Interestingly, atropine treatment significantly increased collagen type I mRNA expression but decreased RGS2 mRNA and protein expression in the sclera of the FDM eyes. CONCLUSIONS: We identified a significant RGS2 upregulation and collagen type I downregulation in the sclera of FDM eyes, which could be partially attenuated by atropine treatment. Our data suggest that targeting dysregulated RGS2 may provide a novel strategy for development of therapeutic agents to suppress myopia progression.

Progress in understanding the association between high myopia and primary open-angle glaucoma.

Many clinical and fundamental studies have shown that high myopia (HM) and glaucoma are closely associated. In particular, the occurrence and progression of primary open-angle glaucoma interact with the progression of HM. Two hypotheses have been proposed to explain the association between the two disorders: the hypertension gene theory and the collagen-related gene theory. HM and primary open-angle glaucoma patients show similar collagen changes and hypersensitive responses to glucocorticoids. Consequently, these common features may hold key information regarding their underlying mechanisms. Advances in life sciences, such as molecular genetics, provide opportunities for clarifying their association at the molecular level. This article reviews available research on the association between these two disorders from the perspectives of epidemiology, clinical manifestation, diagnosis and pathogenic mechanisms.

Meta-analysis of methylprednisolone pulse therapy for Graves' ophthalmopathy.

A meta-analysis was performed to evaluate the efficacy of methylprednisolone pulse therapy for Graves' ophthalmopathy. Eight studies involving 376 patients were included. A higher effective rate was found for patients treated with intravenous glucocorticoids (IVGC) over oral glucocorticoids (OGC) (risk ratio [RR] = 1.48; 95% confidence interval [CI] = 1.18-1.86). The combined IVGC and orbital radiotherapy (OR) was markedly more effective than OGC+OR (RR = 1.40; 95% CI = 1.11-1.77). IVGC resulted in an obvious reduction of clinical activity score (CAS) compared with OGC, with a weighted mean difference (WMD) of 0.86 (95% CI = 0.53-1.18). The WMD for the reduction of the CAS between IVGC+OR and OGC+OR was 0.66 (95% CI = 0.30-1.02). IVGC is an effective treatment and cause fewer adverse events. Limiting the total cumulative dose of methylprednisolone, careful patient selection and monitoring the condition of patients during treatment are necessary.

The multiple roles of autophagy in uveal melanoma and the microenvironment.

PURPOSE: Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults, and effective clinical treatment strategies are still lacking. Autophagy is a lysosome-dependent degradation system that can encapsulate abnormal proteins, damaged organelles. However, dysfunctional autophagy has multiple types and plays a complex role in tumorigenicity depending on many factors, such as tumor stage, microenvironment, signaling pathway activation, and application of autophagic drugs. METHODS: A systematic review of the literature was conducted to analyze the role of autophagy in UM, as well as describing the development of autophagic drugs and the link between autophagy and the tumor microenvironment. RESULTS: In this review, we summarize current research advances regarding the types of autophagy, the mechanisms of autophagy, the application of autophagy inhibitors or agonists, autophagy and the tumor microenvironment. Finally, we also discuss the relationship between autophagy and UM. CONCLUSION: Understanding the molecular mechanisms of how autophagy differentially affects tumor progression may help to design better therapeutic regimens to prevent and treat UM.

Swimming exercise reverses transcriptomic changes in aging mouse lens.

BACKGROUND: The benefits of physical activity for the overall well-being of elderly individuals are well-established, the precise mechanisms through which exercise improves pathological changes in the aging lens have yet to be fully understood. METHODS: 3-month-old C57BL/6J mice comprised young sedentary (YS) group, while aging mice (18-month-old) were divided into aging sedentary (AS) group and aging exercising (AE) group. Mice in AE groups underwent sequential stages of swimming exercise. H&E staining was employed to observe alterations in lens morphology. RNA-seq analysis was utilized to examine transcriptomic changes. Furthermore, qPCR and immunohistochemistry were employed for validation of the results. RESULTS: AE group showed alleviation of histopathological aging changes in AS group. By GSEA analysis of the transcriptomic changes, swimming exercise significantly downregulated approximately half of the pathways that underwent alterations upon aging, where notable improvements were 'calcium signaling pathway', 'neuroactive ligand receptor interaction' and 'cell adhesion molecules'. Furthermore, we revealed a total of 92 differentially expressed genes between the YS and AS groups, of which 10 genes were observed to be mitigated by swimming exercise. The result of qPCR was in consistent with the transcriptome data. We conducted immunohistochemical analysis on Ciart, which was of particular interest due to its dual association as a common aging gene and its significant responsiveness to exercise. The Protein-protein Interaction network of Ciart showed the involvement of the regulation of Rorb and Sptbn5 during the process. CONCLUSION: The known benefits of exercise could extend to the aging lens and support further investigation into the specific roles of Ciart-related pathways in aging lens.

5-Aza-2'-Deoxycytidine Ameliorates Choroidal Neovascularization by Inhibiting the Wnt/ß-Catenin Signaling Pathway.

Purpose: Choroidal neovascularization (CNV) can constitute the final pathology of many ocular diseases and result in severe vision loss. Studies have demonstrated that DNA methylation is critical in retinal development, aging, and disorders. The current work investigated the effects and underlying mechanism of 5-Aza-2'-deoxycytidine (5-aza-dC), a suppressor of DNA methylation, in the pathological progression of CNV. Methods: The DNA methylation profiles of retinal pigment epithelial (RPE)/choroidal complexes in normal and laser-induced CNV mice were assessed by Arraystar Mouse RefSeq Promoter Arrays. The CNV area and blood flow density and intensity were observed by optical coherence tomography angiography, and fluorescence leakage was examined by fundus fluorescein angiography in CNV mice with systemic administration of 5-aza-dC. The effects of 5-aza-dC on the biological functions of bEnd.3 cells were estimated by related assays. Notum gene promoter methylation was measured using bisulfite sequencing PCR. Methyltransferases and Wnt signaling-related genes were detected in animal and cell culture experiments by real-time PCR and immunoblot. Results: Methyltransferases were upregulated, but Notum (a secretion inhibitor of Wnt signaling) was downregulated in the RPE/choroidal complexes of mice with experimental CNV. Intraperitoneal injection of 5-aza-dC inactivated the Wnt pathway and ameliorated the lesion area and the intensity and density of blood flow, as well as the degree of leakage in CNV. In vitro, vascular endothelial growth factor A (VEGFA) stimulation promoted methyltransferases expression and suppressed Notum expression, consequently activating Wnt signaling, whereas exogenous 5-aza-dC reversed VEGFA-induced hyperpermeability, proliferation, migration, and tube formation in bEnd.3 cells via demethylation of Notum promoter. Conclusions: We observed that 5-aza-dC attenuates the growth of CNV by inhibiting the Wnt signaling pathway via promoter demethylation of the Wnt antagonist Notum. These findings provide a theoretical basis for methylation-based treatment with the Notum gene as a potential target for CNV treatment.