Human U90926 orthologous long non-coding RNA as a novel biomarker for visual prognosis in herpes simplex virus type-1 induced acute retinal necrosis.

Acute retinal necrosis (ARN) is a form of infectious uveitis caused by alpha herpesviruses, including herpes simplex virus type 1 (HSV-1). We previously found that the long non-coding RNA (lncRNA) U90926 is upregulated in murine retinal photoreceptor cells following HSV-1 infection, leading to host cell death. However, to date, an orthologous transcript has not been identified in humans. We investigated U90926 orthologous transcript in humans and examined its utility as a prognostic marker for visual acuity in patients with ARN. We identified two human orthologous transcripts (1955 and 592 bases) of lncRNA U90926. The amount of the longer human U90926 transcript was approximately 30- and 40-fold higher in the vitreous fluid of patients with ARN than in those with sarcoidosis and intraocular lymphoma, respectively. Furthermore, the expression of the longer human U90926 transcript in the vitreous fluid was highly correlated with the final best-corrected logarithm of the minimum angle of resolution visual acuity in patients with ARN (r = 0.7671, p = 0.0079). This suggests higher expression of the longer human U90926 transcript in the vitreous fluid results in worse visual prognosis; therefore, expression of the longer human U90926 transcript is a potential negative prognostic marker for visual acuity in patients with ARN.

Inhibition of calpain on oxygen glucose deprivation-induced RGC-5 necroptosis.

The purpose of this study was to investigate the effect of inhibition of calpain on retinal ganglion cell-5 (RGC-5) necroptosis following oxygen glucose deprivation (OGD). RGC-5 cells were cultured in Dulbecco's-modified essential medium and necroptosis was induced by 8-h OGD. PI staining and flow cytometry were performed to detect RGC-5 necrosis. The calpain expression was detected by Western blotting and immunofluorescence staining. The calpain activity was tested by activity detection kit. Flow cytometry was used to detect the effect of calpain on RGC-5 necroptosis following OGD with or without N-acetyl-leucyl-leucyl-norleucinal (ALLN) pre-treatment. Western blot was used to detect the protein level of truncated apoptosis inducing factor (tAIF) in RGC-5 cells following OGD. The results showed that there was an up-regulation of the calpain expression and activity following OGD. Upon adding ALLN, the calpain activity was inhibited and tAIF was reduced following OGD along with the decreased number of RGC-5 necroptosis. In conclusion, calpain was involved in OGD-induced RGC-5 necroptosis with the increased expression of its downstream molecule tAIF.

Necrosis retiniana aguda bilateral en el anciano por varicela zóster / Bilateral acute retinal necrosis due to varicella zóster virus in an elderly patient

CASO CLÍNICO: Presentamos a un paciente de 77 años, con un cuadro de necrosis retiniana aguda con afectación bilateral; la reacción en cadena de la polimerasa (PCR) de la muestra de humor acuoso fue positiva al virus de varicela zóster. En su evolución desarrolla vasculitis de Kyrieleis al mes de inicio del tratamiento y con el análisis por PCR negativo. DISCUSIÓN: La PCR es un método rápido, con una sensibilidad y especificidad del 97%. La actuación debe ser urgente por la rapidez de la progresión. El famciclovir oral es buena alternativa por su mejor biodisponibilidad

CASE REPORT: The case is reported of acute retinal necrosis with bilateral involvement due to Varicella Zoster virus in a 77 year-old man. Polymerase chain reaction (PCR) of aqueous humor was positive for Varicella Zoster virus (VZV). He developed a Kyrieleis’ vasculitis a month after the starting treatment, when the PCR analysis was negative. DISCUSSION: PCR is a quick and safe technique, with a high sensitivity and specificity of 97%, useful to diagnose and monitor the viral activity. The intervention must be urgent, due to the dramatically rapid evolution. Oral famciclovir oral is good alternative owing to its bioavailability

DNA microarray analysis of the uninoculated eye following anterior chamber inoculation of HSV-1.

PURPOSE: To use DNA microarray to analyze the expression patterns of genes in the uninoculated eye following uniocular anterior chamber inoculation of HSV-1. METHODS: On Day 9 following inoculation of 2 x 10( 4) PFU of HSV-1 (KOS strain) or an equivalent volume of tissue culture medium into one anterior chamber of BALB/c mice, the uninoculated eyes were enucleated, pooled, and total RNA was isolated. cDNA was synthesized from the total RNA. The gene expression patterns were inferred based on the hybridization intensities of the probes on the cDNA array. The hybridization signals were globally normalized and filtered. The data were analyzed using hierarchical and gene tree clustering algorithms. Additional uninoculated eyes collected on Day 9 p.i. were stained for F4/80 and CD19. RESULTS: Compared with the uninoculated eye of control mice, 3800 genes were upregulated at least twofold in the contralateral eye of HSV-1-infected mice. Among the 10 most upregulated genes, T cell-specific protein, MHC II antigen A, and MHC II k region locus 2 were upregulated 179-, 164-, and 162-fold, respectively. Ten T-cell receptor-related genes, 61 cytokine and chemokine genes, and 16 MHC genes were upregulated. Furthermore, 11 immunoglobulin and B cell genes and 11 macrophage-related genes were also upregulated. F4/80+ and CD19+ cells were observed on Day 9 p.i. CONCLUSIONS: The DNA microarray results support the idea that T cells and immunomodulatory factors (cytokines, chemokines) are likely to be involved in HSV-1 retinitis. These results also suggest that B cells and/or macrophages play a role in the pathogenesis of HSV-1 retinitis.

Detection of varicella zoster virus DNA and viral antigen in the late stage of bilateral acute retinal necrosis syndrome.

We describe the clinicopathologic and virologic findings in the right, blind eye of an immunocompetent 61-year-old woman. The eye was enucleated 32 months after the clinical onset of a bilateral acute retinal necrosis syndrome. Histopathologic study showed a diffuse, full-thickness, necrotizing retinitis with replacement of sensory retinal structures by glial tissue, occlusive retinal arteritis, granulomatous choroiditis, and optic neuritis with ischemic optic atrophy. Varicella zoster virus could be identified as the causative agent by DNA in situ hybridization and by immunohistochemical stains in mononuclear cells with eosinophilic intracytoplasmic inclusions. Virus was detected only within the choroid and the choriocapillaris. We conclude that these histopathologic and virologic features are consistent with a "burned-out phase" of a varicella zoster virus-induced acute retinal necrosis syndrome.

An association between acute retinal necrosis syndrome and HLA-DQw7 and phenotype Bw62, DR4.

Human leukocyte antigen (HLA) typing was performed on 27 white patients with acute retinal necrosis syndrome. Antigens for the HLA-A, -B, -C, -DR and -DQ loci were determined, and frequencies were compared with racially matched controls. There was a statistically significant increase in the frequency of HLA-DQw7 (11 of 20 [55%] of patients vs 294 of 1546 [19%] of controls, P = .0004, relative risk 5.20) that remained significant at the P = .05 level when the P value was multiplied by the number of antigens tested. The HLA phenotype Bw62, DR4 is also more frequent than in normal control populations (4 of 25 [16%] of patients vs 26 of 1023 [2.6%] of controls, relative risk 7.49). These results support an association between the acute retinal necrosis syndrome and certain HLA specificities and suggest a possible immunogenetic predisposition to the syndrome in some patients.