CMV Papillitis as a Rare Complication of Severe Combined Immunodeficiency Syndrome

Ocular complications of cytomegalovirus (CMV) infection occur in both immunocompromised and immunocompetent patients, but are more common in the former. CMV retinitis is the most common ocular manifestation described in AIDS patients. Severe combined immunodeficiency syndrome (SCID) also results in immunocompromise and increases the risk of ocular CMV. We present a case of CMV papillitis, an ocular CMV manifestation with distinct clinical and angiographic features

Proteomic Insight into the Molecular Function of the Vitreous

<div><p>The human vitreous contains primarily water, but also contains proteins which have yet to be fully characterized. To gain insight into the four vitreous substructures and their potential functions, we isolated and analyzed the vitreous protein profiles of three non-diseased human eyes. The four analyzed substructures were the anterior hyaloid, the vitreous cortex, the vitreous core, and the vitreous base. Proteins were separated by multidimensional liquid chromatography and identified by tandem mass spectrometry. Bioinformatics tools then extracted the expression profiles, signaling pathways, and interactomes unique to each tissue. From each substructure, a mean of 2,062 unique proteins were identified, with many being differentially expressed in a specific substructure: 278 proteins were unique to the anterior hyaloid, 322 to the vitreous cortex, 128 to the vitreous base, and 136 to the vitreous core. When the identified proteins were organized according to relevant functional pathways and networks, key patterns appeared. The blood coagulation pathway and extracellular matrix turnover networks were highly represented. Oxidative stress regulation and energy metabolism proteins were distributed throughout the vitreous. Immune functions were represented by high levels of immunoglobulin, the complement pathway, damage-associated molecular patterns (DAMPs), and evolutionarily conserved antimicrobial proteins. The majority of vitreous proteins detected were intracellular proteins, some of which originate from the retina, including rhodopsin (RHO), phosphodiesterase 6 (PDE6), and glial fibrillary acidic protein (GFAP). This comprehensive analysis uncovers a picture of the vitreous as a biologically active tissue, where proteins localize to distinct substructures to protect the intraocular tissues from infection, oxidative stress, and energy disequilibrium. It also reveals the retina as a potential source of inflammatory mediators. The vitreous proteome catalogues the dynamic interactions between the vitreous and surrounding tissues. It therefore could be an indirect and effective method for surveying vitreoretinal disease for specific biomarkers.</p></div

Human vitreous component dissection images.

<p>The images are shown in the order they are dissected. A. The vitreous core is aspirated using a 23-gauge needle following the removal of the anterior portion of the eye. B. After the vitreous core is aspirated, the anterior hyaloid becomes visible as a translucent ring. This tissue can be grasped with Colibri forceps, cut, and collected. C. The vitreous base is a thick, viscous tissue lying over the ora serrata. This image is for visualization purposes (still containing the anterior iris and lens) to show the pars plicatta, pars plana, ciliary body, and ora serrata. The vitreous base is grasped using Colibri forceps, pulled away from the ora serrata, and cut with Vannas scissors. D. The vitreous cortex is collected by cutting the posterior pole into quadrants and grasping between two sections. It is lifted and cut away from the posterior pole.</p

Unbiased clustering of differentially expressed proteins (p<0.05) in the four human vitreous substructures.

<p>Proteins represented in this cluster analysis were determined by ANOVA, p<0.05. The heatmap is divided into regions: A. proteins highest in the vitreous cortex, B. proteins highest in the anterior hyaloid and the vitreous base, C. proteins highest in the anterior hyaloid, D. proteins absent or low in the vitreous core but represented in the other three tissues, E. proteins highest in the vitreous base, F. proteins in all tissues except the anterior hyaloid, G. proteins unique to the vitreous core, and H. proteins highest in the vitreous core and vitreous cortex.</p

Matrix metalloproteinase 2 (MMP-2) network.

<p>MMP2 is the largest network common to all four regions of the human vitreous humor. MMP-2 is involved in the proteolysis of extracellular matrix proteins, and 108 targets were found in the vitreous.</p

Network analysis reveals the largest unique protein networks for vitreous substructures.

<p>A. The largest hub in the vitreous base was the GSK3 beta hub. B. In the vitreous core, the largest unique network is the ATM network. C, D. The largest hub in the anterior hyaloid is the kallikrein 3 (PSA) network. E, F. The largest network in the vitreous cortex is casein kinase II.</p

Gene ontology (GO) distributions and pathway analysis of human vitreous proteins show tissue similarity.

<p>Expressed proteins of the anterior hyaloid, vitreous cortex, vitreous base, and vitreous core. Proteins were grouped into sub-categories of biological processes, molecular functions, and cellular component for each of the four regions.</p

Proteomic analysis of elevated intraocular pressure with retinal detachment

Purpose: To report a case of elevated intraocular pressure with retinal detachment. Observations: Liquid chromatography and tandem mass spectrometry was performed on the patient aqueous biopsy. Protein levels were analyzed with 1-way analysis of variance (ANOVA) and unbiased clustering. High levels of rod outer segment proteins were not detected, suggesting that this was not a case of Schwartz-Matsuo syndrome. Instead, elevated levels of Hepcidin (HEPC) and Cystatin C (CYTC; candidate biomarkers for primary open angle glaucoma) were detected, suggesting a different, unknown etiology. Conclusions and importance: Molecular diagnoses can differentiate between clinical diagnoses and point to common biomarkers or disease mechanisms