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Due to the genotype–phenotype heterogeneity in retinitis pigmentosa (RP), molecular diagnoses and prediction of disease progression is difficult. This study aimed to report ocular and genetic data from Korean patients with PDE6B-associated RP (PDE6B-RP), and establish genotype–phenotype correlations to predict the clinical course. We retrospectively reviewed targeted next-generation sequencing or whole exome sequencing data for 305 patients with RP, and identified PDE6B-RP in 15 patients (median age, 40.0 years). Amongst these patients, ten previously reported PDE6B variants (c.1280G > A, c.1488del, c.1547T > C, c.1604T > A, c.1669C > T, c.1712C > T, c.2395C > T, c.2492C > T, c.592G > A, and c.815G > A) and one novel variant (c.712del) were identified. Thirteen patients (86.7%) experienced night blindness as the first symptom at a median age of 10.0 years. Median age at diagnosis was 21.0 years and median visual acuity (VA) was 0.20 LogMAR at the time of genetic analysis. Nonlinear mixed models were developed and analysis revealed that VA exponentially decreased over time, while optical coherence tomography parameters linearly decreased, and this was related with visual field constriction. A high proportion of patients with the c.1669C > T variant (7/9, 77.8%) had cystoid macular edema; despite this, patients with this variant did not show a higher rate of functional or structural progression. This study will help clinicians predict functional and structural progression in patients with PDE6B-RP.

We investigated the microvascular changes in eyes with lamellar macular holes (LMHs) using optical coherence tomography angiography (OCTA), compare them between two subtypes of LMH. Tractional and degenerative LMH were differentiated based on the morphological characteristics of OCT. In OCTA images, foveal and parafoveal vessel density (VD) in the superficial and deep capillary plexus (SCP, DCP) and foveal avascular zone (FAZ) area were measured. Eyes that underwent vitrectomy for LMH were included in subgroup analysis. We analysed 63 LMH (42 tractional and 21 degenerative) eyes and 63 control eyes. Compared with degenerative LMH, tractional LMH had better BCVA (p = 0.010), smaller FAZ area (p = 0.001), and higher foveal VD in the SCP (p = 0.130) and DCP (p = 0.002). In degenerative LMH, better BCVA was associated with greater foveal VD in the SCP (p = 0.040) and DCP (p = 0.005), and parafoveal VD in the SCP (p = 0.006). In subgroup analysis, only the tractional LMH group showed significant increases in foveal and parafoveal VDs in the SCP after vitrectomy (p = 0.001 and p = 0.026, respectively). Significant differences in microvascular changes were noted between tractional and degenerative LMH, suggesting that two subtypes are distinct pathogenetic entities.

To investigate the role of synaptic zinc in the ASD pathogenesis, we examined zinc transporter 3 (ZnT3) null mice. At 4–5 weeks of age, male but not female ZnT3 null mice exhibited autistic-like behaviors. Cortical volume and neurite density were significantly greater in male ZnT3 null mice than in WT mice. In male ZnT3 null mice, consistent with enhanced neurotrophic stimuli, the level of BDNF as well as activity of MMP-9 was increased. Consistent with known roles for MMPs in BDNF upregulation, 2.5-week treatment with minocycline, an MMP inhibitor, significantly attenuated BDNF levels as well as megalencephaly and autistic-like behaviors. Although the ZnT3 null state removed synaptic zinc, it rather increased free zinc in the cytosol of brain cells, which appeared to increase MMP-9 activity and BDNF levels. The present results suggest that zinc dyshomeostasis during the critical period of brain development may be a possible contributing mechanism for ASD.