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In an ex vivo rat glaucoma model using dissected retinas, the neurosteroid allopregnanolone (AlloP) protects retinal ganglion cells (RGCs) via GABR/GABAA receptors. To determine the involvement of macroautophagy/autophagy in neuroprotection by AlloP, we examined the effects of autophagy activators, rapamycin and torin 2, and autophagy inhibitors, bafilomycin A1 and SAR405, on retinal retinal morphology and expression of MAP1 LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) and SQSTM1 (sequestosome 1). Administration of rapamycin or torin 2 exerted partial histological neuroprotection, while combined administration of AlloP with bafilomycin A1 or SAR405 induced severe degeneration in a hyperbaric condition. Electron microscopic analyses showed that the addition of AlloP significantly increased autophagosomes and degenerative autophagic vacuoles in the retinal nerve fiber layer. Immunoblotting showed that the addition of AlloP or autophagic activators increased the lipidated form of LC3B (LC3B-II) and suppressed SQSTM1. Moreover, bafilomycin A1 increased LC3B-II and SQSTM1 protein levels in the presence of AlloP without changes in corresponding mRNAs compared to AlloP-treated retinas in a hyperbaric condition. These data indicate that AlloP likely induces a protective form of autophagy in this model. In an in vivo rat model of glaucoma, we also observed neuroprotective effects of AlloP. Injection of polystyrene microbeads into the anterior chamber increased intraocular pressure about 3-fold and induced RGC apoptosis. A single intravitreal injection of AlloP or autophagy activators prevented apoptosis and protected RGCs with autophagy activation. We conclude that AlloP may serve as a potential therapeutic agent for the treatment of glaucoma via diverse mechanisms. Abbreviations: 2HBCD: 2-Hydroxypropyl)-β-cyclodextrin; 3-MA: 3-methyladenine; AlloP: allopregnanolone; AP: autophagosome; AVd: degradative autophagic vacuoles; GCL: ganglion cell layer; INL: inner nuclear layer; IOP: intraocular pressure; IPL: inner plexiform layer; LC3B-I: cytosolic form of LC3B; LCB-II: lipidated form of LC3B; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mPTP: mitochondrial permeability transition pore; NDS: neuronal damage score; NFL: nerve fiber layer; OH: ocular hypertension; ON: optic nerve; ONL: outer nuclear layer; OPL: outer plexiform layer; p-STR: scotopic threshold response; RGC: retinal ganglion cells; RT-PCR: real-time reverse transcription polymerase chain reaction; SQSTM1: sequestosome 1; TUNEL: TdT-mediated dUTP Nick End Labeling [ABSTRACT FROM AUTHOR]

Purpose: To report the occurrence probability of disc haemorrhage (DH) and risk factors for it in otherwise healthy Japanese normal‐tension glaucoma (NTG) patients who had lower normal intraocular pressure (IOP) and were followed without treatment for 5 years. Methods: A prospective observational study. Normal‐tension glaucoma (NTG) patients with IOP consistently ≤15 mmHg without treatment were enrolled. The presence or absence of DH was checked semi‐annually on the fundus photographs by three independent observers, while patients were followed without treatment. Cox proportional hazards model taking inter‐eye correlation into consideration was adopted to identify risk factors for DH occurrence. The main outcomes were DH occurrence probability during 5‐year period and its risk factors. Results: One hundred seventeen eyes of 90 patients with mean age of 54.1 years, mean deviation value of −3.6 decibels and mean IOP during follow‐up of 12.4 mmHg were included. Disc haemorrhage (DH) was observed at least once in 34 eyes and more than twice in 15 eyes during the follow‐up. The DH occurrence probability at 5 years was 31% (95% confidence interval: 21–40%), and lower myopic refraction (HR = 1.18; p = 0.018), higher IOP during follow‐up (HR = 1.35; p = 0.047) and presence of DH at baseline (HR = 4.19; p = 0.002) were its risk factors. Conclusion: Disc haemorrhage (DH) occurrence probability of Japanese healthy NTG patients with mean IOP of 12.4 mmHg and no systemic and/or topical treatment was 31% at 5 years. Lower myopic refraction, higher IOP and its existence at baseline were its risk factors. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the course of changes in choroidal morphology after immersion of the foot in warm water at 40°C using enhanced depth imaging optical coherence tomography (EDI-OCT)., Methods: Forty-three right eyes of 43 healthy participants were included. Changes in choroidal morphology were determined using EDI-OCT to evaluate subfoveal choroidal thickness (SCT). Systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP, respectively) were also measured to determine systemic circulatory dynamics at baseline, immediately after immersion (0 min), and 10, 20, and 30 min after immersion., Results: Immediately after immersion, SBP, DBP, and MBP were significantly declined versus baseline. In contrast, the SCT was significantly increased after warm water immersion. However, all these parameters did not change significantly compared to the baseline within 30 min., Conclusion: In the normal eye, parasympathetic nerve activity induced by warming stimuli increases choroidal morphology in response to a decrease in systemic circulatory activity, which normalizes within 30 min. The findings of this study may provide basic data for the prevention and treatment of various choroidal diseases in which sympathetic hyperactivity is involved in the pathogenesis., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Toh et al.)

Purpose: The purpose of this study was to investigate risk factors for progression in the superior and inferior hemi-visual fields (hemi-VFs) and the corresponding hemi-disc/retinas in eyes with normal tension glaucoma (NTG)., Methods: A 5-year prospective follow-up of 90 patients with NTG with untreated intraocular pressure (IOP) consistently ≤ 15 mm Hg was conducted. The IOP and Humphrey Perimeter measurements and disc/retina stereo-photographs were taken every 3 and 6 months, respectively. Risk factors for progression in the superior and inferior hemi-VFs and in the superior and inferior hemi-disc/retinas were investigated., Results: The mean total deviation values decreased at -0.50 ± 0.76 and -0.13 ± 0.34 dB/year in the superior and inferior hemi-VFs, respectively (P < 0.001). In the superior hemi-VF, the risk factor for faster progression was greater long-term IOP fluctuation (P = 0.022). In the inferior hemi-VF, the risk factors were disc hemorrhage (DH), greater myopic refraction, body mass index (BMI), and vertical cup-to-disc ratio (v-C/D; P < 0.05). The progression probability was 47.7 ± 6.0 and 17.7 ± 4.7% at 5 years in the superior and inferior hemi-disc/retinas respectively (P < 0.001), and DH was a risk factor for progression in both (P = 0.001)., Conclusions: In NTG eyes, greater BMI, myopia, and v-C/D are characteristic risk factors for faster progression in the superior half of the optic nerve head (ONH), whereas long-term IOP fluctuation is the significant risk factor in the inferior half of the ONH, whereas DH is a risk factor in both., Translational Relevance: Different risk factors were identified in superior and inferior hemifields in NTG eyes.