AMP-activated protein kinase regulates alternative pre-mRNA splicing by phosphorylation of SRSF1.

AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis by inhibiting anabolic processes and activating catabolic processes. Recent studies have demonstrated that metformin, which is an AMPK activator, modifies alternative precursor mRNA (pre-mRNA) splicing. However, no direct substrate of AMPK for alternative pre-mRNA splicing has been reported. In the present study, we identified the splicing factor serine/arginine-rich splicing factor 1 (SRSF1) as a novel AMPK substrate. AMPK directly phosphorylated SRSF1 at Ser133 in an RNA recognition motif. Ser133 phosphorylation suppressed the interaction between SRSF1 and specific RNA sequences without altering the subcellular localization of SRSF1. Moreover, AMPK regulated the SRSF1-mediated alternative pre-mRNA splicing of Ron, which is a macrophage-stimulating protein receptor, by suppressing its interaction with exon 12 of Ron pre-mRNA. The findings of this study revealed that the AMPK-dependent phosphorylation of SRSF1 at Ser133 inhibited the ability of SRSF1 to bind RNA and regulated alternative pre-mRNA splicing.

Effect of magnification error and axial length on circumpapillary capillary density and retinal nerve fiber layer thickness.

This study aimed to evaluate the effect of magnification error and axial length (AL) on circumpapillary capillary density (cpCD) and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in healthy eyes. Seventy-two healthy eyes of 72 subjects with AL 24.7 ± 1.5 mm (range: 20.9-28.0 mm) were enrolled in this retrospective cross-sectional study and underwent optical coherence tomography angiography scanning. Magnification corrected measurement areas were obtained using AL upon which corrected cpCD, cpRNFLT values were determined. Relationships between AL and the percentage difference between corrected and uncorrected values (ΔcpCD, ΔcpRNFLT) as well as the effect of AL on magnification corrected cpCD, cpRNFLT were evaluated. ΔcpCD significantly increased with AL in the global, inferior nasal and superior nasal sectors (all p < 0.001). ΔcpRNFLT significantly increased with AL in global and all sectors (all p < 0.001) and the correlations were significantly stronger than that of ΔcpCD-AL in all sectors (all p < 0.001). Corrected cpCD did not associate with AL while corrected cpRNFLT demonstrated a significant positive association with AL in the global (p = 0.005) and temporal sector (p < 0.001). Magnification error led to a significant underestimation of cpCD in eyes with longer AL although its underestimation and the effect of AL was smaller in comparison to that of cpRNFLT.

Structure Function Relationships of Vessel Density and Retinal Nerve Fiber Layer Thickness in Early Glaucomatous Eyes With High Myopia.

Purpose: The purpose of this study was to evaluate the structure function relationship of circumpapillary vessel density (cpVD) with visual field sensitivity (VFS) and compare its characteristics with circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in early glaucomatous (EG) and normal eyes with and without high myopia (HM). Methods: Seventy-five EG (mean deviation > -6 dB) and 7 normal eyes with HM (axial length [AL] >26.5 mm) and 111 EG and 11 normal eyes without HM were enrolled in this retrospective cross-sectional study. All patients underwent circumpapillary optical coherence tomography (OCT) and OCT angiography (OCTA) scanning with the Cirrus HD-6000 with AngioPlex OCTA (Carl Zeiss Meditec, Dublin, CA, USA). Structure function correlations were determined by comparing global, superior, inferior, and Garway-Heath sectoral values for cpVD and cpRNFLT with its corresponding 24-2 and 10-2 VFS of Humphrey Visual Field (HFA) analyzer. Results: CpVD showed no significant correlations with AL except for the nasal sector (P = 0.044), whereas cpRNFLT demonstrated significant positive association with AL in the global (P = 0.024), nasal (P = 0.020), and temporal (P < 0.001) sectors. In HM eyes, global and sectoral cpVD significantly correlated with corresponding VFS in all 24-2/10-2 VF sectors (all P < 0.05). CpVD-VFS correlation was significantly stronger than cpRNFLT-VFS in the nasal sector of HM eyes (P = 0.002) and temporal and inferior temporal sector of eyes without HM (P = 0.008 and P = 0.042, respectively). Conclusions: In EG eyes with HM, cpVD was less affected by AL in comparison to cpRNFLT and cpVD-VFS correlation was significant in all 24-2/10-2 VF sectors. AL-associated advantages of cpVD-VFS over cpRNFLT-VFS were observed.

Impact of rigid gas-permeable contact lens on keratometric indices and corneal thickness of keratoconus eyes examined with anterior segment optical coherence tomography.

PURPOSE/AIM: Detecting keratoconus (KC) progression helps determine the surgical indication for corneal cross-linking (CXL). This retrospective observational study aimed to examine changes in keratometric indices and corneal thickness in patients with KC who used rigid gas-permeable (RGP) contact lenses. MATERIALS AND METHODS: This study involved 31 eyes (31 patients) diagnosed with KC. No patient had used RGP or any other type of contact lenses for at least 1 month. Corneal topographic data were obtained using three-dimensional anterior segment optical coherence tomography before and after >1 month of RGP lens use. RESULTS: The average and maximum keratometry values changed after using an RGP lens (-1.05 ± 1.92 D, p < 0.01 and -1.65 ± 4.20 D, p = 0.04, respectively); the spherical component of the anterior corneal surface became significantly smaller (p = 0.02). No change was observed in the central or thinnest corneal thickness values. Keratometric changes were greater in eyes with severe KC than in those with moderate KC (p = 0.014). CONCLUSIONS: Keratometry and spherical components of the anterior corneal surface values decreased after RGP lens use; keratometric changes were greater in eyes with severe KC than in those with moderate KC. Corneal progression indices, including corneal thickness, posterior keratometry, and irregular astigmatism values, mostly remained unchanged. It is important to consider these findings when evaluating corneal topography of KC and preparing CXL.

Diagnostic ability and sectoral structure-function relationship of circumpapillary and macular superficial vessel density in early glaucomatous eyes.

This study aimed to evaluate the diagnostic ability and sectoral structure function relationship of circumpapillary vessel density (cpVD) and macular vessel density (mVD) with optical coherence tomography angiography (OCTA) in early glaucomatous (EG) eyes. 224 EG eyes of 167 patients (mean deviation (MD) > - 6 dB) and 70 normal eyes of 70 subjects were enrolled in this retrospective cross-sectional study. All patients underwent OCT and OCTA scanning. Diagnostic abilities were evaluated with area under receiver operating characteristic curves (AUROC). Structure function relationships of superior, inferior and Garway-Heath sectoral values with its corresponding visual field (VF) sensitivity were determined using linear mixed models. AUROCs were 0.798, 0.621, 0.876 and 0.835 for cpVD, mVD, circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and ganglion cell-inner plexiform layer, respectively. AUROC of cpVD was significantly lower than cpRNFLT (P = 0.010) and higher than mVD (P < 0.001). All Garway-Heath sectors of cpVD significantly correlated with its corresponding VF sensitivity except for the nasal sector. MVD also showed significant structure function relationship and the correlations were stronger in the perifoveal region (6 mm annulus) than in the parafoveal region (3 mm annulus). CpVD demonstrated moderate diagnostic ability and both cpVD and mVD demonstrated significant association with VF sensitivity in EG eyes.

Severe Adult Still's Disease Complicated by Purtscher-Like Retinopathy Treated with Intravenous Pulse Methylprednisolone and Tocilizumab.

Adult Still's disease (ASD) is a rare systemic inflammatory disorder in which ocular manifestations have rarely been described. We report a 29-year-old Japanese woman with a rare case of refractory ASD complicated by Purtscher-like retinopathy. She was diagnosed with ASD and started on a high dose of oral prednisolone. Two days after the initiation of the treatment, she presented with blurred vision in the left eye, and the funduscopic examination revealed bilateral Purtscher-like retinopathy. Despite treatment with high-dose oral prednisolone for 2 weeks, she developed macrophage activation syndrome. Considering the severity of ASD, intravenous pulse methylprednisolone therapy and tocilizumab injection were administered. Although all the laboratory data and Purtscher-like retinopathy gradually improved, nerve fiber layer defect (NFLD) in both eyes appeared and visual field defect remained corresponding to the NFLD. In conclusion, Purtscher-like retinopathy might be useful as a poor prognostic factor of ASD, which needs appropriate systemic immunosuppressive treatment. Early detection and long-term follow-up of Purtscher-like retinopathy is important because it has the possibility of developing permanent visual field defect.