Here, we report our studies of immune-mediated regulation of Zika virus (ZIKV), herpes simplex virus 1 (HSV-1), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the human cornea. We find that ZIKV can be transmitted via corneal transplantation in mice. However, in human corneal explants, we report that ZIKV does not replicate efficiently and that SARS-CoV-2 does not replicate at all. Additionally, we demonstrate that type III interferon (IFN-λ) and its receptor (IFNλR1) are expressed in the corneal epithelium. Treatment of human corneal explants with IFN-λ, and treatment of mice with IFN-λ eye drops, upregulates antiviral interferon-stimulated genes. In human corneal explants, blockade of IFNλR1 enhances replication of ZIKV and HSV-1 but not SARS-CoV-2. In addition to an antiviral role for IFNλR1 in the cornea, our results suggest that the human cornea does not support SARS-CoV-2 infection despite expression of ACE2, a SARS-CoV-2 receptor, in the human corneal epithelium.

Leber congenital amaurosis type nine is an autosomal recessive retinopathy caused by mutations of the NAD+ synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1, patients do not manifest pathologies other than retinal degeneration. Here we demonstrate that widespread NMNAT1 depletion in adult mice mirrors the human pathology, with selective loss of photoreceptors highlighting the exquisite vulnerability of these cells to NMNAT1 loss. Conditional deletion demonstrates that NMNAT1 is required within the photoreceptor. Mechanistically, loss of NMNAT1 activates the NADase SARM1, the central executioner of axon degeneration, to trigger photoreceptor death and vision loss. Hence, the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, highlighting an unexpected shared mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway and identifies SARM1 as a therapeutic candidate for retinopathies.

. Purpose:  Laser speckle flowgraphy (LSFG) can be used to non‐invasively visualize the haemodynamics of choroidal circulation and the vascular pattern. The purpose of this study was to examine the ability of LSFG to quantitatively evaluate blood flow velocity at the macula in patients with Vogt–Koyanagi–Harada (VKH) disease before and after systemic corticosteroid therapy. Methods:  Prednisolone (200 mg/day) was systemically administered in 10 VKH disease patients with serous retinal detachment at the macular area. The drug was gradually tapered to zero over a 6‐month period. Laser speckle flowgraphy measurements were taken in the 20 eyes of these patients at their initial visit and at 1, 4 and 12 weeks after the onset of therapy. Square blur rate (SBR), a quantitative index of relative blood flow velocity, was calculated using LSFG. Results:  Serous retinal detachment resolved within 4 weeks after treatment and visual acuities improved to > 1.0 in almost all cases. There were significant increases in average SBR at the macula at 4 weeks after treatment compared with at 1 week after treatment, and also at 12 weeks after treatment compared with at 4 weeks after treatment. Conclusions:  These results suggest that systemic corticosteroid therapy improves inflammation‐related impairment in choroidal blood flow velocity at the macula. Laser speckle flowgraphy can evaluate the effect of systemic corticosteroid therapy by enabling comparisons between measurements of blood flow velocity, which is considered to reflect inflammation activity in the choroid.

PurposeThe aims of this study were to analyze optical coherence tomography (OCT) imaging of large macular holes (MHs) treated with inverted internal limiting membrane (ILM) flap technique and to perform a histological examination of an ILM-like membrane tissue obtained during vitrectomy.Patients and methodsThis is a retrospective observational case study. Nine patients, comprising of five males and four females, showing large and myopic MHs, underwent pars plana vitrectomy (PPV) with inverted ILM flap technique assisted by brilliant blue G (BBG) staining. Ophthalmological findings including visual acuity and OCT were investigated based on medical records. Formalin-fixed paraffin-embedded tissue section of an ILM-like membrane was submitted for immunohistochemistry with glial fibrillary acidic protein (GFAP).ResultsILM was clearly stained with BBG in eight patients, whereas the ILM in one case revealed no staining with BBG during PPV. Visual acuities improved to >0.2 LogMAR in six patients. The complete closure of MH following PPV with inverted ILM technique was eventually achieved in all patients determined by OCT imaging (100%). Only one patient showed recovery of ellipsoid zone and interdigitation zone following the surgery. Elongation of outer nuclear layer was noted in three eyes. The ILM-like membrane not stained with BBG histologically revealed an amorphous structure admixed with GFAP-positive mononuclear cell infiltration.ConclusionPPV with inverted ILM flap technique achieved 100% closure rates with favorable configuration at an initial surgery in large MHs. Our histopathological data also suggest that even BBG staining-negative membrane may be a useful material for autologous transplantation to the hole.

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