Insolubility and aggregation of crystallins are common features in cataracts. CYP51 has been identified as a novel candidate gene for cataracts; however, its associated phenotypes remain unconfirmed. We investigated the role of FF-MAS, synthesized by CYP51, in αA-crystallin solubility and lens transparency. FF-MAS was administered to HLE-B3 cells expressing αA-crystallin (R116C) and to rats with selenite-induced cataracts. Lens transparency was assessed using slit-lamp photography. Congo red staining and transmission electron microscopy were used to analyze lens uniformity. Western blotting and immunofluorescence were employed to detect αA-crystallin aggregation. Additionally, we evaluated the effects of FF-MAS on apoptosis, antioxidant capacity, and protein homeostasis. In HLE-B3 cells, FF-MAS reduced αA-crystallin (R116C) aggregation. In rats with selenite-induced cataracts, FF-MAS increased αA-crystallin solubility, enhanced antioxidant capacity, reduced HSP90 levels, and protected α-tubulin and AQP-0, thereby improving lens uniformity and transparency. Inhibition of CYP51 by ketoconazole also led to cataract formation in rats and mice and increased apoptosis in HLE-B3 cells. Exogenous supplementation with FF-MAS inhibited these processes. FF-MAS plays a significant role in improving αA-crystallin solubility and lens transparency. Elevating FF-MAS levels may offer a novel approach to preventing and alleviating cataracts.

Background:Dry eye disease (DED) is a global health burden with limited effective and safe treatments. Quercetin (Qu) possesses potent anti-inflammatory and antioxidant activities, but its poor solubility and short half-life restrict ophthalmic use. Methods:Qu‑loaded PEGylated liposomes (Qu‑PL) were prepared by thin‑film hydration and incorporated into gellan gum to form an ion‑responsive in situ gel (Qu‑PL‑ISG). The formulation was characterized for particle size (PS), zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency (EE), short-stability, in vitro release, cytotoxicity, ocular irritation, mucoadhesion, ocular surface retention, pharmacokinetics, and therapeutic efficacy in a BAC‑induced DED mouse model. Network pharmacology and molecular docking were used to generate testable hypotheses on possible mechanisms of Qu in DED. Results:Qu‑PL‑ISG had a PS of 173.33 ± 1.27 nm, a ZP of -46.87 ± 0.95 mV, and an EE of 88.85 ± 1.41%. It released 46% of Qu over 72 h and remained stable for 21 days at 4 °C, with no cytotoxicity or irritation. Compared with Qu‑PL, Qu‑PL‑ISG exhibited higher mucoadhesive force (3783.5 ± 125.2 vs. 1986.2 ± 145.7 dyne/cm2) and longer ocular surface retention (45 vs. 20 min). Ocular bioavailability (AUC0‑1 80) in cornea, conjunctiva, and tears increased 2.79-, 1.47- and 1.44-fold, respectively. In DED mice, 0.2% Qu‑PL-ISG restored tear secretion, reduced corneal staining, repaired epithelial thickness, increased goblet cell density, and lowered corneal IL-1β and TNF-α levels, with efficacy comparable to 0.05% cyclosporine A. Network pharmacology and molecular docking were used as computational tools to predict that Qu may act on DED through multi‑target interactions (TNF, NF‑κB, STAT3, IL-1β, AKT1, IL-6, Src) and pathways (IL-17, PI3K-Akt, TNF signaling), though these findings require experimental validation. Conclusion:Qu‑PL‑ISG is a safe, ion‑activated in situ gel that significantly enhances Qu bioavailability and anti‑inflammatory efficacy, showing promise for DED treatment.

To compare clinical outcomes of implantable collamer lens (ICL) combined with femtosecond laser-assisted arcuate keratotomy (FSAK) and toric implantable collamer lens (TICL) for high myopia with moderate-to-low astigmatism corrections. In this single-center, non-randomized, parallel-group study, patients with high myopia and moderate-to-low astigmatism (0.75D 2.00D) received either ICL+FSAK or TICL treatment and underwent a 3-month postoperative follow-up. We compared the efficacy, safety, predictability, and stability between the two groups, along with outcomes including vector analysis of astigmatism, intraocular pressure (IOP), corneal endothelial cell density (ECD), vault, modulation transfer function (MTF) cutoff, Strehl ratio (SR), and objective scatter index (OSI). At three months postoperatively, median manifest astigmatism in ICL+FSAK group was − 0.25 diopter (D), similar to that in TICL group was − 0.25D (P = 0.774). At all timepoints, two groups were comparable in terms of uncorrected distance visual acuity, corrected distance visual acuity, manifest spherical equivalent, manifest astigmatism, efficacy index, safety index. At 1 day, 1 month, and 3 months postoperatively, median surgically induced astigmatism in ICL+FSAK group were 0.74 D, 0.79 D, and 0.82 D, smaller than those in TICL group (0.86 D, 0.99 D, and 1.01 D) (P < 0.05). Similarly, median correction index postoperatively were 0.69 and 0.75 in ICL+FSAK group, smaller than those in TICL group (0.82 and 0.84) at 1 month and 3 months (P < 0.05). At all timepoints, no significant differences in difference vector or absolute value of angle error occurred between two groups.Similar results also occurred in IOP, ECD, vault, MTF cutoff, SR, and OSI. TICL resulted in higher SIA and CI compared to FSAK, but there was no significant difference in postoperative manifest astigmatism. Therefore, both methods are excellent choices for high myopia with moderate-to-low astigmatism. ChiCTR2400092267. The registration date is November 13, 2024. Clinical Trial Registry: Chinese Clinical Trial Registry.

We aimed to compare the visual outcomes associated with different postoperative spherical equivalents (SEs) following trifocal intraocular lens implantation in patients with cataracts across different refractive states. This study included 156 eyes of 100 patients. The corrected distance visual acuity, uncorrected distance visual acuity, uncorrected intermediate visual acuity, uncorrected near visual acuity, SE, defocus curve, visual quality and satisfaction were compared postoperatively. For non-axial myopia, group B showed better visual acuity at + 0.5 D and + 1.0 D (P = 0.013 and P < 0.001), but worse visual acuity at -3.5 D and − 4.0 D defocus (P = 0.013 and P = 0.004), with better far vision satisfaction (P = 0.030). For mild to moderate axial myopia, group A showed worse visual acuity at + 0.5 D defocus (P = 0.006) and + 1.0 D (P < 0.001). For high axial myopia, the postoperative UNVA was better in group A (P = 0.010). Group A exhibited better visual acuity at -3.0 D, -3.5 D and − 4.0 D (P = 0.018, P = 0.002 and P < 0.001), but worse visual acuity at + 0.5 D and + 1.0 D (P = 0.002 and P < 0.001), with a higher near vision satisfaction (P = 0.021). Trifocal IOLs can provide good visual outcomes. In patients with non-axial myopia, residual emmetropia to mild hyperopia SE may be associated with better far vision satisfaction. For patients with high axial myopia, residual myopia SE may be associated with better UNVA and improved near vision satisfaction, not affecting distant or intermediate vision satisfaction.

The morphological, mechanical, and cellular response of lenses to acute elevation of intraocular pressure (IOP) remained largely unknown. Therefore, we carried out a comprehensive study on the changes of mouse lenses after acute elevation of IOP, and explored the underlying molecular biological mechanism. Acute ocular hypertension was induced in the eye of adult C57BL/6J mice by cannulation of the anterior chamber. Gross morphology and ultrastructure of the lenses were evaluated by the slit lamp, OCT examinations, immunofluorescence staining, immunohistochemistry, and electron microscope, and physical properties were also measured. RNA sequencing analysis was applied to detect relevant transcriptional alterations. We found that subcapsular lens opacities appeared after the IOP spike. The volume, weight, and water content were subsequently decreased. While the lens capsules and LECs attached displayed no significant structural changes after IOP elevation compared with control lenses, the subcapsular cortex was compressed and disorganized. RNA sequencing analysis showed the biological changes of lenses involve various aspects such as cell adhesion and lens fiber remodeling. Lastly, we confirmed that brinzolamide eye drop was able to reduce the AQP1 level, and improve both the transparency and the water content of the lenses after IOP elevation. In conclusion, our study updates the fundamental insight towards the biomechanical response of lenses and their correlation with cataract development, paving the way for further exploration of protection towards lenses after the IOP spike.

Objective To compare and characterize the dynamic changes in accommodation, vergence, and higher-order aberrations in patients with moderate to high myopia undergoing implantable collamer lens (ICL) implantation and femtosecond laser–assisted laser in situ keratomileusis (FS-LASIK), so as to provide an evidence base for postoperative visual function training and to inform more rational surgical decision-making for myopic patients. Methods This was a prospective, non-randomized controlled study. A total of 63 patients (126 eyes) with moderate to high myopia, treated at the Army Specialty Medical Center between May 2025 and November 2025, were enrolled. Eligible subjects were 18–35 years of age, had a spherical equivalent of −6.00 D to −10.00 D, and a preoperative best-corrected visual acuity (BCVA) of ≥0.8. Binocular visual function and higher-order aberrations were assessed using standard clinical tests and the OPD-Scan III system at four time points: preoperatively and at 1 week, 1 month, and 3 months postoperatively. Binocular vision testing included amplitude of accommodation, binocular accommodative facility, positive and negative relative accommodation, heterophoria, accommodative convergence/accommodation (AC/A) ratio, binocular cross-cylinder (BCC), and positive and negative fusional vergence. Higher-order aberration measurements comprised total ocular HOAs, coma, trefoil, and spherical aberration. Parameters related to accommodation, vergence, and higher-order aberrations at each time point after ICL and FS-LASIK were subjected to statistical comparison and longitudinal analysis. Results In the ICL group, mean spherical equivalent (SE) at 1 week, 1 month, and 3 months postoperatively was significantly improved compared with preoperative values (p < 0.001). The amplitude of accommodation showed an initial postoperative decrease followed by recovery toward baseline (p < 0.01), and PRA exhibited a similar pattern of early reduction with subsequent return to preoperative levels (p < 0.01). By 3 months, binocular accommodative facility was significantly higher than before surgery (p < 0.01). Both distance and near exophoria were markedly reduced after ICL implantation (p < 0.01 for both). Distance base-in (BI) break and recovery points were significantly lower postoperatively than at baseline (both p < 0.01), and near BI break and recovery points were also significantly decreased at all postoperative time points (both p < 0.01). In contrast, distance base-out (BO) break and recovery points were significantly higher at each postoperative visit than preoperatively (both p < 0.01). Total ocular higher-order aberrations (HOAs) increased significantly after surgery (p < 0.05). Trefoil aberration rose initially and then declined toward preoperative levels (p < 0.01), whereas spherical aberration increased significantly and remained elevated at 3 months (p = 0.003). In the FS-LASIK group, mean SE at 1 week, 1 month, and 3 months postoperatively was also significantly better than preoperative SE (p < 0.001). Pairwise postoperative comparisons showed that mean SE at 3 months was significantly lower (i.e., closer to emmetropia) than at 1 week. The amplitude of accommodation again decreased initially and then recovered toward baseline (p < 0.01), and PRA followed the same trend, with a significant early decline and subsequent return to preoperative levels (p = 0.017). Binocular accommodative facility at 3 months was significantly improved relative to baseline (p < 0.05). Distance and near exophoria were both significantly reduced after FS-LASIK (p < 0.01 for each). Postoperative distance BI break and recovery points were significantly lower than preoperative values (both p < 0.01), and near BI break and recovery points were likewise significantly reduced at all postoperative time points (both p < 0.01). Distance BO recovery points were significantly higher after surgery than at baseline (p = 0.038). Total ocular HOAs increased significantly following FS-LASIK (p < 0.001), and coma, trefoil, and spherical aberration were all significantly higher postoperatively than preoperatively (all p < 0.01); among these, coma and spherical aberration at 3 months were significantly greater than at 1 week. In between-group comparisons, residual SE at 1 week was higher in the FS-LASIK group than in the ICL group, whereas at 1 month the positive BCC value was greater in the ICL group than in the FS-LASIK group. At 3 months, total ocular HOAs, coma, and spherical aberration were all significantly higher in the FS-LASIK group than in the ICL group (p < 0.01 for all comparisons). Conclusion Both ICL implantation and femtosecond FS-LASIK are effective treatments for the correction of myopic refractive error. In the early postoperative period, patients may experience transient changes in accommodative and vergence function; however, these typically return to preoperative levels over time, with some patients even showing improvement. Compared with FS-LASIK, ICL implantation provides greater stability and predictability of postoperative refractive status and induces fewer higher-order aberrations.

Proliferative diabetic retinopathy (PDR) is among the primary causes of blindness in individuals with diabetes. Elevated lactate levels have been identified as a critical biomarker associated with the prognosis of PDR. While significant lactate accumulation has been observed in the vitreous fluid of PDR patients, the detailed pathways through which lactate impacts pathological neovascularization remain insufficiently elucidated. The study employed single-cell RNA sequencing (scRNA-seq) to identify and characterize lactate-associated cell type in PDR patients. Key gene expression profiles and molecular pathways associated with lactate metabolism were analyzed. In vitro experiments were conducted using microglial cell cultures treated with high-glucose conditions (50 mM) to assess the induction of lactate metabolism-related genes. Additionally, an oxygen-induced retinopathy (OIR) mouse model was used to evaluate the impact of abemaciclib, an FDA-approved proliferation inhibitor, on retinal neovascularization. To the best of our knowledge, this investigation is the first to delineate a novel microglial subset, designated as MKI67+ microglia, distinguished by robust upregulation of genes implicated in lactate metabolic processes and proliferation, such as MKI67, PARK7 and LDHA, as well as a pronounced enrichment of glycolysis-associated molecular pathways. This unique cell type promotes angiogenesis by interacting with endothelial cells via secreted phosphoprotein 1 (SPP1)-Integrin alpha 4 (ITGA4) signaling. In vitro experiments have shown the use of 50 mM high glucose to simulate microglia in PDR environment and observe its promotion of vascular proliferation. In the in vivo OIR model, treatment with abemaciclib, a FDA-approved proliferation inhibitor, significantly reduced neovascularization. The identification of MKI67+ microglia as a cell type strongly associated with lactate metabolism provides a novel perspective on the mechanisms underlying PDR onset. These findings expand our understanding of the cellular and metabolic dynamics in PDR, emphasizing potential implications for targeted therapeutic interventions.

Purpose To evaluate the efficacy and safety of intravitreal injection of conbercept for the treatment of macular edema secondary to central retinal vein occlusion (CRVO-ME). Methods Patients with CRVO were randomly divided into the treatment (conbercept injection) and control groups (sham injection) at a ratio of 2:1. The primary endpoint was the mean changes in best-corrected visual acuity (BCVA) from baseline to month 6. Results From baseline to month 6, the mean change in BCVA letters were 13.6 ± 12.1 (P < 0.0001) and − 2.2 ± 16.5 (P = 0.2188) in the treatment and control groups. From baseline to month 12, the mean change in BCVA letters were 14.4 ± 13.8 (P < 0.0001) and 3.0 ± 17.6 (P < 0.0001). The mean reduction of CRT from baseline to month 6 were 138.4 ± 99.4 µm (P < 0.0001) and 35.1 ± 98.8 µm (P = 0.0018). From baseline to month 12, the mean reduction values of CRT were 145.1 ± 105.1 µm (P < 0.0001) and 81.7 ± 107.9 µm (P < 0.0001). No new safety events were identified. Conclusions Intravitreal injection of conbercept has definite efficacy and expected controllable safety in patients with CRVO-ME, providing a more flexible strategy for conbercept in the clinical treatment of CRVO-ME. Trial Registration: ClinicalTrials.gov Identifier: NCT03223714, Date: July 21, 2017.

PURPOSE:To evaluate and contrast the effectiveness and safety of two conbercept treatment protocols-a three-dose treat-and-extend (3+T&E) regimen and a three-dose pro re nata (3+PRN) regimen-in Chinese patients diagnosed with neovascular age-related macular degeneration (nAMD). METHODS:Eligible patients, who had not undergone anti-VEGF intraocular injections within 3 months prior to enrollment, were randomly assigned to either the 3+T&E or 3+PRN regimen. The 3+T&E group received at least three monthly injections, with subsequent visit intervals extended based on disease activity assessment. The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 48, using a predefined noninferiority threshold. RESULTS:Among 501 participants (249 in 3+T&E, 252 in 3+PRN), approximately half had prior anti-VEGF treatment. At 48 weeks, both regimens showed significant BCVA improvements (+9.9 for 3+PRN, +8.6 for 3+T&E; p = .208), with comparable rates of ≥15-letter gains (32.12% for 3+PRN, 30.77% for 3+T&E; p = .827). The 3+PRN group received fewer injections (mean 6.4 vs. 6.9 in 3+T&E; p = .028) but had shorter intervals between injections (6.93 weeks vs. 7.46 weeks in 3+T&E; p = .010). Drug-related adverse events occurred in 5% of patients, with ocular events evenly distributed and minimal cardiovascular events reported. CONCLUSION:Both 3+T&E and 3+PRN conbercept regimens effectively improved visual and anatomical outcomes in Chinese nAMD patients. The 3+T&E regimen was noninferior to 3+PRN in improving BCVA from baseline to week 48. The 3+T&E regimen enabled longer injection intervals while 3+PRN regimen with less injections is more cost-effective while maintaining a comparable safety profile. Treatment plan tailored to an individual patient's situation appears necessary.

To compare the visual effect and subjective satisfaction of cataract patients with different refractive states after trifocal intraocular lens (IOL) implantation. This retrospective study describes 134 eyes of 86 patients that were implanted with trifocal IOL (TFNT00). Patients were allocated into three groups according to their preoperative axial length (AL): A group (AL ≤ 24 mm), B group (24 mm < AL < 26 mm), and C group (AL ≥ 26 mm). Postoperative visual acuity, defocus curve, visual quality and subjective satisfaction were collected and compared, and the postoperative follow-up time was at least 3 months (3 months to 3 years). The uncorrected intermediate visual acuity (UIVA) and uncorrected near visual acuity (UNVA) of A group was significantly better than B group (P = 0.008 and P = 0.016). The UNVA of C group was significantly better than B group (P = 0.047). The defocus curve showed that the visual acuity of three groups from 40 cm to 5 m was better than 0.16 (LogMAR). The near vision satisfaction of B group was significantly lower than A group and C group (P<0.001 and P = 0.004). For cataract patients with different refractive states, trifocal IOL implantation can provide good visual and refractive outcomes. For cataract patients with low and moderate myopia, the UIVA and UNVA were worse, and the subjective satisfaction of near vision was also worse than the hyperopia and emmetropia and the high myopia.

PURPOSE:To investigate the 3-month outcomes of visual performance and satisfaction of patients with high myopia after implantation of trifocal intraocular lens (IOL). SETTING:Army Medical Center of PLA, Chongqing, China. DESIGN:Retrospective case series. METHODS:Patients were divided to 2 groups according to the spherical equivalent (SEQ) (high myopia ≤-6.0 diopters [D] and nonhigh myopia >-6.0 D). Corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA) at 5 m, uncorrected intermediate visual acuity (UIVA) at 60 cm, uncorrected near visual acuity (UNVA) at 40 cm, defocus curve, refraction, visual quality, and satisfaction were compared at 3 months postoperatively. RESULTS:Of 57 patients (89 eyes) enrolled, 32 eyes (36%) were highly myopic and 57 eyes (64%) were nonhighly myopic. At 3 months, both groups exhibited smooth defocus curves, with better visual acuity at 0 D, -0.5 D, and -2.0 D. Mean SEQ was -0.19 (-0.25, 0.00) D and 0.00 (-0.25, 0.00) D in the highly myopic and nonhighly myopic groups, respectively, with no significant difference ( P = .34). There were no significant differences between the 2 groups in CDVA, UDVA, UIVA, UNVA, spectacle independence, or satisfaction ( P > .05). Higher-order aberrations (HOAs) and trefoil aberration were greater in the highly myopic group ( P < .05). CONCLUSIONS:Trifocal IOL implantation provides satisfactory full-range visual acuity on the premise of no complications, with a spectacle independence rate of more than 90%. Although HOAs and trefoil aberration were greater in patients with high myopia, they achieve comparable visual acuity and spectacle independence rates, with a high satisfaction.

The global prevalence of myopia is becoming increasingly severe, with epidemiological models predicting that by 2050, approximately 50% of the world's population will be affected by myopia, and about 10% will suffer from high myopia. The incidence of high myopia is projected to increase fivefold, making it the leading cause of irreversible vision impairment. Myopia often leads to various complications and has been associated with other ocular diseases, including early-onset cataracts, age-related macular degeneration, and primary open angle glaucoma. As a result, the control and management of myopia have become ongoing and long-term research priorities. The pathogenesis of myopia involves complex multisystem interactions. Current mainstream theories focus primarily on choroidal hypoxia-induced scleral remodeling, with neurotransmitters such as acetylcholine and dopamine playing regulatory roles. However, recent studies have increasingly suggested that changes in nutritional intake, including proteins, fats, and cholesterol, may also be related to myopia development. The role of lipid metabolism in the onset and progression of myopia has gradually attracted growing attention. Therefore, this review aims to systematically elucidate the molecular mechanisms of lipid metabolism regulatory networks in axial myopia, integrating multidimensional factors to provide a theoretical foundation for precision intervention strategies.

As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells (RGCs). It is widely accepted that the level of intraocular pressure (IOP) is a major risk factor in human glaucoma, and reduction of IOP level is the principally most well-known method to prevent cell death of RGCs. However, clinical studies show that lowering IOP fails to prevent RGC degeneration in the progression of glaucoma. Thus, a comprehensive understanding of glaucoma pathological process is required for developing new therapeutic strategies. In this study, we provide functional and histological evidence showing that optic nerve defects occurred before retina damage in an ocular hypertension glaucoma mouse model, in which oligodendroglial lineage cells were responsible for the subsequent neuropathology. By treatment with clemastine, an Food and Drug Administration (FDA)-approved first-generation antihistamine medicine, we demonstrate that the optic nerve and retina damages were attenuated via promoting oligodendrocyte precursor cell (OPC) differentiation and enhancing remyelination. Taken together, our results reveal the timeline of the optic neuropathies in glaucoma and highlight the potential role of oligodendroglial lineage cells playing in its treatment. Clemastine may be used in future clinical applications for demyelination-associated glaucoma.

Purpose. The reference range for the preoperative anterior chamber angle width for ICL surgery is unclear. Our objective was to assess the clinical effect and the range of anterior chamber angle width of posterior-chamber implantable collamer lens V4c (ICL V4c) implantation in patients with anterior chamber depth (ACD) < 2.8 mm. Methods. Patients who underwent ICL V4c implantation with shallow ACD were included in this retrospective study. The patients’ uncorrected and corrected distance visual acuity, angle of trabecular-iris (TIA), angle-opening distance (AOD500), trabecular-iris space area (TISA500), corneal endothelial cell density, vault, retinal nerve fiber layer thickness, intraocular pressure, visual field, and complications were analyzed. Results. Forty-one patients (68 eyes) completed at least 12 months of follow-up (median follow-up, 30 months). The effectiveness and safety indices were 1.09 ± 0.13 and 1.04 ± 0.21, respectively. The preoperative TIA values on the nasal and temporal sides were 39.78 ± 7.68 degree (range, 25.8-65.1 degree) and 41.54 ± 8.03 degree (range, 28.5-63.00 degree). Forty-seven eyes had uncorrected distance visual acuity ≥1.0, and 55 had corrected distance visual acuity ≥1.0 at the last follow-up visit. The TIA, AOD500, and TISA500 on the nasal and temporal sides were significantly reduced compared to those before surgery (all P<0.01); no eye had an angle closure or elevated intraocular pressure. The ICL V4c vault was 290.88 ± 153.36 μm (range, 60.0-880.0 μm). No severe complications occurred in any patient. Conclusions. In patients with myopia with shallow ACD (2.55-2.79 mm), a preoperative TIA >25.8° is safe and effective for a relatively long time after surgery; however, an extended long-term close follow-up is needed.

AbstractIntroductionRepeated exposure to cocaine induces microglial activation. Cocaine exposure also induces a release of high mobility group box‐1 (HMGB1) from neurons into the extracellular space in the nucleus accumbens (NAc). HMGB1 is an important late inflammatory mediator of microglial activation. However, whether the secretion of HMGB1 acts on microglia or contributes to cocaine addiction is largely unknown.MethodsRats were trained by intraperitoneal cocaine administration and cocaine‐induced conditioned place preference (CPP). Expression of HMGB1 was regulated by viral vectors. Activation of microglia was inhibited by minocycline. Interaction of HMGB1 and the receptor for advanced glycation end products (RAGE) was disrupted by peptide.ResultsCocaine injection facilitated HMGB1 signaling, together with the delayed activation of microglia concurrently in the NAc. Furthermore, the inhibition of HMGB1 or microglia activation attenuated cocaine‐induced CPP. Box A, a specific antagonist to interrupt the interaction of HMGB1 and RAGE, abolished the expression of cocaine reward memory. Meanwhile, the inhibition of HMGB1–RAGE interaction suppressed cocaine‐induced microglial activation, as well as the consolidation of cocaine‐induced memory.ConclusionAll above results suggest that the neural HMGB1 induces activation of microglia through RAGE, which contributes to the consolidation of cocaine reward memory. These findings offer HMGB1–RAGE axis as a new target for the treatment of drug addiction.

Activated astrocytes are a primary source of inflammatory factors following traumatic optic neuropathy (TON). Accumulation of inflammatory factors in this context leads to increased axonal damage and loss of retinal ganglion cells (RGCs). Therefore, in the present study, we explored the role of the astrocyte G protein-coupled estrogen receptor (GPER) in regulating inflammatory factors following optic nerve crush (ONC), and analyzed its potential regulatory mechanisms. Overall, our results showed that GPER was abundantly expressed in the optic nerve, and co-localized with glial fibrillary acidic proteins (GFAP). Exogenous administration of G-1 led to a significant reduction in astrocyte activation and expression of inflammation-related factors (including IL-1β, TNF-α, NFκB, and p-NFκB). Additionally, it dramatically increased the survival of RGCs. In contrast, astrocytes were activated to a greater extent by exogenous G15 administration; however, RGCs survival was significantly reduced. In vitro, GPER activation significantly reduced astrocyte activation and the release of inflammation-related factors. In conclusion, activation of astrocyte GPER significantly reduced ONC inflammation levels, and should be explored as a potential target pathway for protecting the optic nerve and RGCs after TON.

PURPOSE:To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN:Randomized, double-masked, multicenter, active-controlled, noninferiority phase II study. PARTICIPANTS:A total of 231 treatment-naive and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. METHODS:Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa, or 2 mg aflibercept groups. Participants in all groups received 3 initial monthly loading doses, followed by treatment every 8 weeks, with assessment every 4 weeks up to week 52. MAIN OUTCOME MEASURES:The primary end point was the mean best-corrected visual acuity (BCVA) change from baseline to week 36. The prespecified noninferiority margin was set as -5 letters (80% confidence interval [CI]). RESULTS:Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, and +12.0 letters, respectively; least squares mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. CONCLUSIONS:Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile. FINANCIAL DISCLOSURE(S):The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose. To compare corneal higher-order aberrations (HOAs), refractive error, and ocular biological parameters before and after phacoemulsification combined with goniosynechialysis (Phaco-GSL) in primary angle closure/glaucoma (PAC/PACG) patients with different axial lengths (ALs). Methods. In this prospective study, cataract patients diagnosed with PAC/PACG were categorized into two groups based on their ALs: the short AL group (AL ≤ 22.5 mm) and the normal AL group (22.5 < AL ≤ 24.5 mm). The pre- and postsurgery measurements of intraocular pressure (IOP) and best-corrected visual acuity (BCVA) were conducted at 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months. Additionally, the assessments included corneal HOAs, the number of antiglaucoma medications, visual field parameters, manifest refraction, and other ocular biological parameters before surgery and at the final follow-up. Results. Prior to surgery, the two groups exhibited no significant differences, except for AL, curvature value, and Z (4, 0) of the posterior corneal surface (all P<0.01). Following surgery, BCVA improved, and IOP decreased significantly in both groups (P<0.01). Both anterior and total corneal HOAs, along with Z (3, −3), increased in the two groups (all P<0.05), with the normal AL group exhibiting a significantly greater increase in total cornea Z (3, −3) than the short AL group (P=0.047). The normal AL group also exhibited a slight tendency towards hyperopia (P<0.01). Significant changes were observed in the visual field index and mean deviation in both groups (P<0.05). Conclusions. Phaco-GSL resulted in an increased corneal HOAs, particularly trefoil, with variations based on the patient’s AL. Patients with normal ALs tended to shift towards hyperopia after surgery.

Purpose: To explore the effect of the variation of pupil diameter (PD) and intraocular pressure (IOP) induced by femtosecond laser treatment on the subsequent phacoemulsfication and intraocular lens implantation. And whether the application of 0.1% pranoprofen could significantly reduce the miosis and increased IOP caused by femtosecond laser treatment in femtosecond laser-assisted cataract surgery (FLACS). Methods: In this study, patients were pretreated with (trial group) or without (control group) topical 0.1% pranoprofen. The PD and IOP were measured at different time points within 30 min after the completion of the femtosecond laser treatment. Results: The comparisons of the two groups showed the PD of patients pretreated with 0.1% pranoprofen was significantly larger than that of the control only at 15 min after FLACS (P = 0.046), and there was no significant difference in IOP at any time point (P > 0.05). Neither the ratio of significant miosis (PD <= 5 mm) nor intraocular hypertension (IOP >= 30 mmHg) was significantly different between the control group (1.72%, 6.67%) and the trial group (1%, 4.17%) (P > 0.05). Conclusions: The PD and IOP of patients undergoing FLACS showed fluctuations within a small range. The rates of significant miosis and intraocular hypertension are very low, it is safe for surgeons to complete the follow-up procedures within 30 min after femtosecond laser treatment. Pretreatment with 0.1% pranoprofen exerted a slight, albeit significant prophylactic effect preventing pupil miosis. However, it provided only a limited benefit in patients undergoing FLACS without other complications.

PURPOSE. Microglial clearance of axonal debris is an essential response for management of traumatic optic neuropathy. Inadequate removal of axonal debris leads to increased inflammation and axonal degeneration after traumatic optic neuropathy. The present study investigated the role of CD11b (Itgam) in axonal debris clearance and axonal degeneration. METHODS. Western blot and immunofluorescence were used to detect CD11b expres-sion in the mouse optic nerve crush (ONC) model. Bioinformatics analysis predicted the possible role of CD11b. Cholera toxin subunit B (CTB) and zymosan were used to assay phagocytosis by microglia in vivo and in vitro, respectively. CTB was also used to label functionally intact axons after ONC. RESULTS. CD11b is abundantly expressed after ONC and participates in phagocytosis. Microglia from Itgam-/- mice exhibited more significant phagocytosis of axonal debris than wild-type microglia. In vitro experiments confirmed that the CD11b gene defect in M2 microglia leads to increased insulin-like growth factor-1 secretion and thus promotes phagocytosis. Lastly, following ONC, Itgam-/- mice exhibited elevated expression of neurofilament heavy peptide and Tuj1, along with more intact CTB-labeled axons when compared with wild-type mice. Moreover, the inhibition of insulin-like growth factor-1 decreased CTB labeling in Itgam-/- mice after injury. CONCLUSIONS. CD11b limits microglial phagocytosis of axonal debris in traumatic optic neuropathy, as demonstrated by increased phagocytosis with CD11b knockout. The inhi-bition of CD11b activity may be a novel approach to promote central nerve repair.