The Wisconsin Department of Health Services received notice of an unusual number of cases of retinoblastoma in a small geographic area. Retinoblastoma is a rare pediatric eye cancer that strikes children aged <5 years. The reporters of these cases were concerned that they may be part of a cancer cluster. Cancer clusters are unusual numbers of cases in a defined geographic area over a defined period of time. They are believed to be caused by shared environmental or occupational risk factors. It is not known to what extent these risk factors play a role in retinoblastoma incidence.

Lacritin is an abundantly expressed glycoprotein in tear fluid and plays key roles in immune response, tear secretion, and bacterial killing. These biological functions are tightly regulated through several biochemical mechanisms including multimerization, proteolysis, and alternative splicing, especially within its C-terminal domain. Given its critical role at the ocular surface, lacritin is currently under investigation as a diagnostic biomarker and therapeutic candidate for dry eye disease (DED). However, despite over three decades since its initial discovery, the functional significance of the O-glycans that comprise more than 50% of its molecular weight remains largely unknown. To address this gap, we leveraged mass spectrometry (MS)-based glycoproteomics, AlphaFold 3.0, and molecular dynamics (MD) to explore the structural role of site-specific O-glycans on C-terminal lacritin. In doing so, we identified distinct glycosylation profiles between monomeric and multimeric lacritin, particularly at glycosites located near crosslinking residues (Lys101 and Lys104) that modulate multimer formation. Based on our glycoproteomics data, we performed MD simulations on monomer and multimer glycoforms and revealed that O-glycans may participate in intramolecular glycan-protein interactions that influence its structure and the spatial arrangement of Lys101 and Lys104. Differences in the solvent accessible surface area (SASA) and root mean squared fluctuation (RMSF) of these residues further suggested that proximal O-glycosylation could affect their ability to participate in crosslinking. To test these predictions, we performed in vitro crosslinking assays and demonstrated reduced TGM2-mediated multimerization of glycosylated versus unmodified lacritin. Finally, we show that recombinant glycoforms bearing O-glycan patterns similar to endogenous lacritin multimers are enriched after TGM2 crosslinking. Taken together, these findings underscore a central role for lacritin O-glycans in affecting structural topology and multimerization with implications for its downstream biological activity.

Marfan syndrome (MFS) is an autosomal dominant multisystemic connective tissue disorder caused by pathogenic variants in the FBN1 gene and characterized by cardiovascular, ocular, and musculoskeletal manifestations. Ocular findings commonly include strabismus, refractive error, ectopia lentis, glaucoma, and retinal detachment. We report the case of a 14-year-old male patient with a variant of uncertain significance (VUS) in the FBN1 gene and a phenotype compatible with the Marfan spectrum. Clinical data were obtained from ophthalmic examination, ocular imaging, echocardiographic findings, and next-generation sequencing. The patient underwent ophthalmic evaluation as part of the workup for suspected MFS and had a best-corrected visual acuity of 20/30-1 and 20/30+1 in the right and left eyes, respectively. Slit-lamp examination showed minimal bilateral inferior lens subluxation (ectopia lentis) upon downgaze, and fundus examination showed bilateral optic disc cupping with otherwise normal posterior segment findings. Optical coherence tomography showed symmetric retinal nerve fiber layer thickness and a mild inter-eye difference in the cup-to-disc ratio. Based on bilateral optic disc cupping, the patient was considered a glaucoma suspect; however, glaucoma was not established. Systemic findings resulted in a Ghent systemic score of 7, while cardiovascular evaluation showed no evidence of aortic root dilation. Next-generation sequencing using an aortopathy panel identified a heterozygous FBN1 c.7004G>A (p.Arg2335Gln) variant classified as a VUS. This case highlights the diagnostic challenges of interpreting FBN1 variants of uncertain significance in patients with a highly suggestive Marfan spectrum phenotype and underscores the importance of comprehensive phenotypic assessment for clinical diagnosis and long-term management. The identified VUS cannot establish disease causality or provide definitive molecular confirmation. Rather, this case contributes phenotypic information regarding an unresolved FBN1 variant that may inform future genotype-phenotype correlation and variant re-evaluation as additional evidence becomes available.

Hierarchical organization of colloidal building blocks can give rise to emergent collective behavior inaccessible to individual constituents. This study shows that polycrystalline giant carbon nanodots and carbonaceous nanosheets, produced from a single reaction, can serve as building blocks for hierarchically organized active matter. In organic media, the giant CNDs spontaneously assemble into nanosheet architectures that form fluorescent microswimmers, exhibiting sustained propulsion, corkscrew-like helical motion, and nonreciprocal body deformation required for locomotion at low Reynolds numbers. Time-resolved trajectory analysis reveals interaction-mediated synchronization between neighbouring swimmers, including hydrodynamically coupled double-helical motion and long-range dynamic influence between distant assemblies. At higher concentrations, continuous optical excitation drives collective motion, producing macroscopic vortex formation observable directly by the naked eye. The assemblies further undergo fractal growth into leaf- and root-like crystalline architectures in the condensed state spanning centimeter length scales, highlighting the emergence of hierarchical organization across multiple dimensions. Interestingly, the assembled state induces an aggregation-driven fluorescence red-shift of more than 100 nm, generating yellow-orange emissive microswimmers from otherwise blue-emitting carbon nanodots. Exposure to trace water destabilizes the assemblies, releasing blue-emitting nanodots and disrupting the active state, thereby enabling rapid visual detection of small amounts of water in several organic solvents through distinct emission-colour transitions, including white-light generation at intermediate compositions. These findings establish structurally evolved carbon nanostructures as a platform for interaction-driven active matter and broaden the conceptual scope of carbon nanodot research from isolated fluorescent nanoparticles toward hierarchically organized, dynamically adaptive functional systems.

Axenfeld-Rieger anomaly is a rare, congenital disorder characterized by neural crest-derived defects of the ocular anterior segment, traditionally presenting with high bilateral symmetry. This case report highlights a significant diagnostic pitfall involving a profoundly asymmetric presentation of bilateral Axenfeld-Rieger anomaly in a systemically healthy 23-year-old male student, complicated by late-onset secondary congenital glaucoma and an associated cystoid macular edema. Due to severe, unilateral microcystic epithelial and stromal corneal edema confined strictly to the left eye, the underlying congenital structural anomalies were heavily masked. This advanced unilateral decompensation led two independent tertiary institutions to misdiagnose the condition as an acquired, strictly unilateral iridocorneal endothelial (ICE) syndrome. Meticulous bilateral evaluation resolved the diagnostic dilemma. While the right eye was completely asymptomatic, with normal visual parameters, gonioscopy unmasked silent, subclinical congenital angle anomalies, including an anteriorly inserted iris root and isolated iridocorneal strands distributed across all four quadrants. Crucially, bilateral specular microscopy revealed an absence of pathognomonic ICE cell changes in both eyes, establishing the true bilateral, developmental nature of the pathology. Initial multi-drug medical intraocular pressure-lowering therapies, including the Rho kinase inhibitor ripasudil 0.4%, failed to reverse the advanced left corneal endothelial failure, ultimately necessitating a successful left penetrating keratoplasty for visual rehabilitation. This case underscores the clinical necessity of routine, thorough bilateral gonioscopic and specular evaluations of the clinically unaffected companion eye to avoid diagnostic errors when a young adult presents with sudden, highly asymmetric glaucoma.