Background. Compound Xueshuantong capsule (CXC) and Hexuemingmu tablet (HXMMT) are two important Chinese patent medicines (CPMs) frequently used to treat proliferative diabetic retinopathy (PDR), especially when complicated with vitreous hemorrhage (VH). However, a network pharmacology approach to understand the therapeutic mechanisms of these two CPMs in PDR has not been applied. Objective. To identify differences in the active ingredients between CXC and HXMMT and to comparatively predict and further analyze the molecular targets shared by these CPMs and PDR. Materials and methods. The differentially expressed messenger RNAs (mRNAs) between normal retinal tissues in healthy individuals and active fibrovascular membranes in PDR patients were retrieved from the Gene Expression Omnibus database. The active ingredients of CXC and HXMMT and the targets of these ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. The intersections of the CPM (CXC and HXMMT) targets and PDR targets were determined. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, and the ingredient-target networks, protein-protein interaction networks, and KEGG-target (KEGG-T) networks were constructed. Results. CXC contains 4 herbs, and HXMMT contains 19. Radix salviae is the only herb common to both. CXC had 34 potential therapeutic targets in PDR, while HXMMT had these 34 and 10 additional targets. Both CPMs shared the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessel diameter and size, vasoconstriction, smooth muscle contraction, hemostasis, and blood coagulation. The shared pathways included the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, and IL-17 signaling pathway. Conclusions. Both CXC and HXMMT include components effective at treating PDR and affect the following main processes: response to reactive oxygen species and oxidative stress, regulation of blood vessels, and blood coagulation. Radix salviae, the only herb common to both CPMs, contains many useful active ingredients. The PDR-CXC and PDR-HXMMT networks shared 34 common genes (RELA, HSPA8, HSP90AA, HSP90AB1, BRCA, EWSR1, CUL7, HNRNPU, MYC, CTNNB1, MDM2, YWHAZ, CDK2, AR, FN1, HUWE1, TP53, TUBB, EP300, GRB2, VCP, MCM2, EEF1A1, NTRK1, TRAF6, EGFR, PRKDC, SRC, HDAC5, APP, ESR1, AKT1, UBC, and COPS5), and the PDR-HXMMT network has 10 additional genes (RNF2, VNL, RPS27, COPS5, XPO1, PARP1, RACK1, YWHAB, and ITGA4). The top 5 pathways with the highest gene ratio in both networks were the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, relaxin signaling pathway, IL-17 signaling pathway, and focal adhesion. Additional pathways such as neuroactive ligand-receptor interaction, chemokine signaling pathway, and AMPK signaling pathway were enriched with HXMMT targets. Thus, HXMMT has more therapeutic targets shared by different active ingredients and more abundant gene functions than CXC, which may be two major reasons why HXMMT is more strongly recommended than CXC as an auxiliary treatment for new-onset VH secondary to PDR. However, the underlying mechanisms still need to be further explored.

JOURNAL/nrgr/04.03/01300535-202304000-00039/figure1/v/2026-05-25T155121Z/r/image-tiff Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration. However, morphological assessments of retinorecipient regions are limited by the opacity of brain tissue. In this study, we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury. Specifically, we performed light-sheet imaging of whole brain tissue after a clearing process. We found that pseudorabies virus 724 (PRV724) mostly infected retinal ganglion cells, and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains. Unexpectedly, PRV724-traced neurons were more widely distributed compared with data from previous studies. We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus, intergeniculate leaflet, ventral lateral geniculate nucleus, central amygdala, basolateral amygdala, Edinger-Westphal nucleus, and oculomotor nucleus, but not the superior vestibular nucleus, red nucleus, locus coeruleus, gigantocellular reticular nucleus, or facial nerve nucleus. Our findings demonstrate that the tissue clearing technique, combined with retrograde trans-synaptic viral tracing, can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury. Thus, our approach may be useful for future estimations of optic nerve injury and regeneration.

Aim. To establish a classification tree model in DR screening and to compare the DR screening accuracy between the classification tree model and the logistic regression model in type 2 diabetes mellitus (T2DM) patients based on OCTA variables. Methods. Two hundred forty-one eyes of 241 T2DM patients were included and divided into two groups: the development cohort and the validation cohort. Optical coherence tomography angiography (OCTA) images were acquired in these patients. The data of foveal avascular zone area, superficial capillary plexus (SCP) density, and deep capillary plexus (DCP) density were exported after automatically analyzing the macular 6 × 6 mm OCTA images, while the data of radial peripapillary capillary plexus (RPCP) density was exported after automatically analyzing the optic nerve head 4.5 × 4.5 mm OCTA images. These OCTA variables were adopted to establish and validate the logistic regression model and the classification tree model. The area under the curve (AUC), sensitivity, specificity, and statistical power for receiver operating characteristic curves of two models were calculated. Results. In the logistic regression model, best-corrected visual acuity (BCVA) (LogMAR) and SCP density were entered (BVCA : OR= 60.30, 95% CI= [2.40, 1513.82], $p$ = 0.013; SCP density: OR= 0.86, 95% CI= [0.78, 0.96], $p$ = 0.006). The AUC, sensitivity, and specificity for detecting early-stage DR (mild to moderate NPDR) in the development cohort were 0.75 (95% CI: [0.66, 0.85]), 63%, and 83%, respectively. The AUC, sensitivity, and specificity in the validation cohort were 0.75 (95% CI: [0.66, 0.84]), 79%, and 72%, respectively. In the classification tree model, BVCA (LogMAR), DM duration, SCP density, and DCP density were entered. The AUC, sensitivity, and specificity for detecting early-stage DR were 0.72 (95% CI: [0.60, 0.84]), 66%, and 76%, respectively. The AUC, sensitivity, and specificity in the validation cohort were 0.74 (95% CI: [0.65, 0.83]), 74%, and 72%, respectively. The statistical power of the development and validation cohorts in two models was all more than 99%. Conclusions. Compared to the logistic regression model, the classification tree model has similar accuracy in predicting early-stage DR. The classification tree model with OCTA variables may be a simple tool for clinical practitioners to identify early-stage DR in T2DM patients. Moreover, SCP density is significantly reduced in mild-to-moderate NPDR eyes and might be a biomarker in early-stage DR detection. Further improvement and validation of the DR diagnostic model are awaiting to be performed.

Laser-induced hypertension in nonhuman primates is used to mimic human glaucoma, the leading cause of irreversible blindness. In this protocol, we detail steps for laser-induced ocular hypertension in nonhuman primates by laser photocoagulation of the trabecular meshwork and subsequent intracameral injection. We further describe recording and evaluation of intraocular pressure changes and peripapillary retinal nerve fiber layer thickness. This protocol can assist researchers improve the success rate and repeatability of the procedure and reduce the number of nonhuman primates needed.

Aim: To develop a suitable radiation optic neuropathy (RON) diagnostic model based on optical coherence tomography angiography (OCTA) and to reveal the correlation between endocrine and OCTA indexes in nasopharyngeal carcinoma (NPC) patients with radiation encephalopathy (RE). Methods: This retrospective cross-sectional study included seventy-seven male NPC patients with RE following radiotherapy (41 non-RON and 36 RON). Endocrine and OCTA indexes were collected. The macular and peripapillary vessel density (VD) were automatically analyzed using AngioVue 2.0 of the RTVue XR Avanti device. The OCTA indexes were included in the multivariable binary logistic regression model between non-RON and RON. For all RE patients, a multiple linear regression was performed between each of the OCTA indexes and the endocrine indexes. Results: Compared to non-RON, enlarged foveal avascular zone (FAZ) area, reduced superficial vascular plexus (SVP) VD and radial peripapillary capillary plexus density, reduced full retinal thickness, ganglion cell complex thickness and peripapillary retinal nerve fiber layer thickness were observed in RON. Foveal VD in the SVP was included in the RON diagnostic model. Free triiodothyronine (FT3) showed a significantly negative correlation with the FAZ area but showed a significantly positive correlation with foveal VD in the SVP and deep vascular plexus, peripapillary VD and thickness and parafoveal and perifoveal thickness. Conclusions: OCTA may be useful for diagnosing RON in male NPC patients with RE following radiotherapy. Reduced FT3 and foveal VD in SVP may be sensitive in screening RON in these patients.

To report a case of bilateral lens subluxation associated with homocystinuria that had been previously misdiagnosed with high myopia, amblyopia, and keratoconus. A 19-year-old Asian female presented with progressive bilateral visual decline and hand tremors over 10 years. Slit-lamp examination, anterior segment optical coherence tomography, genetic and metabolic testing were performed to confirm the diagnosis of homocystinuria. Surgical intervention was undertaken to improve visual acuity. Anterior segment imaging documented bilateral lens subluxation and microspherophakia before and after intraocular lens suture fixation surgery. Postoperatively, her vision improved to 20/20. This case demonstrates the importance of basic slit-lamp examination especially after cycloplegic refraction for unusual myopia progression and the need to recognize associated systemic symptoms in ophthalmic practice.