The function and mechanism of SYTL5 in papillary thyroid carcinoma (PTC) are still unclear. In this research, we found that SYTL5 was significantly overexpressed in PTC tissues compared with normal thyroid tissues. SYTL5 downregulation significantly weakened the proliferative, migratory, and invasive abilities of PTC cells. In addition, upregulated SYTL5 could promote cancer progression by activating the NF-κB signaling pathway. RAC1b expression is positively associated with SYTL5, and overexpressed RAC1b abrogated the antitumor effect after SYTL5 inhibition. In conclusion, our findings identify the oncogenic role of SYTL5 in PTC by activation of the NF-κB signaling pathway, thus facilitating PTC development and progression.

Purpose. This study aimed to describe and analyze the clinical features of 20 eyes of 15 primary vitreoretinal lymphoma (PVRL) patients. Methods. This was a retrospective case series and a review of the literature. Fifteen PVRL patients (20 affected eyes) referred between February 2011 and December 2019 were recruited, and their medical records were retrospectively reviewed. Results. Among these 15 PVRL patients, seven were men (46.67), and five had bilateral PVRL (33.33). The median onset age was 66±9.26 years and six (40) patients had central nervous system (CNS) involvement, and two of them died of CNS-related complications. The ocular symptoms varied from decreased vision to binocular diplopia. The ocular manifestations were diverse and involved both the anterior and posterior segments, including the vitreous cells, subretinal white-yellow lesions, cotton-wool spots, and ophthalmoplegia. The rate of misdiagnosis and failure to diagnose was 100, and 30 of them were misdiagnosed as uveitis. We found five cases revealing rare characteristics of this malignancy. Among them, there were two cases with mild hypertensive retinopathy exhibiting cotton-wool spots, one case mimicking age-related macular degeneration (AMD), one case with systemic lupus erythematosus (SLE), and one patient had extraocular muscle involvement. To the best of our knowledge, we reported PVRL exhibiting cotton-wool spots as the main manifestation and coexisting with extraocular myopathy for the first time. Conclusions. PVRL is a rare intraocular malignancy that commonly masquerades as uveitis. As the clinical signs and symptoms are atypical, ophthalmologists must carefully examine patients to avoid misdiagnosis or a failure to diagnose. Cotton-wool spots and extraocular myopathy might be the dominant initial symptoms in PVRL patients, and AMD should be considered a differential diagnosis of PVRL. SLE patients under immunosuppressive treatment could have spontaneous PVRL.

AIM: To investigate the mitochondrial dysfunction-related genes and their regulatory mechanisms involved in primary open angle glaucoma (POAG), which is characterized by retinal ganglion cell loss. METHODS: Multi-omic summary-data-based Mendelian randomization (SMR) integrating methylation quantitative trait loci (mQTL), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) were performed for mitochondrial genes with genome-wide association studies (GWAS) of POAG and related traits [intraocular pressure (IOP), macular retinal nerve fiber layer thickness (mRNFL), and macular ganglion cell-inner plexiform layer thickness (mGCIPL)]. Bayesian colocalization was used to support shared causal variants and to define evidence tiers across omics. SPATA20 expression was assessed in a mouse glaucoma model by immunofluorescence and Western blot. RESULTS: SMR identified 64 mitochondrial genes associated with at least one outcome, including ALDH18A1 for POAG and MRPL55 for mRNFL. eQTL analysis revealed 212 associations, prioritizing MRPL20, SLC25A26, ALAS1, and GLYCTK for POAG, ACAD10 for IOP, ALDH6A1, GRPEL2, and YARS2 for mRNFL, and ALDH6A1, TIMM21, TIMM29, LARS2, and METAP1D for mGCIPL. The pQTL layer implicated 21 proteins, including BOLA1 for POAG. Cross-omic synthesis supported 18 genes by ≥2 omics layers. SPATA20 was supported by all three layers, showed a consistent negative association with mRNFL, and in mice was transiently upregulated in retina, with expression in the ganglion cell layer. CONCLUSION: Multi-omic SMR with colocalization highlights mitochondrial genes for POAG and related traits and nominates SPATA20 as a leading cross-omics signal for mRNFL.