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| October 2007 | Inside IOVS | Volume 48/10 |
Dichoptic mfVEP in Glaucoma
The conventional multifocal VEP has shown the ability to diagnose glaucomatous field loss. Arvind et al (p. 4590) investigated the ability of simultaneous binocular (dichoptic) stimulus presentation with multifocal VEP to detect glaucomatous field loss. While it reduced testing time and accurately identified proven field defects, it also identified losses in some areas that showed structural damage to the optic disc but were normal on Humphrey field analysis. Dichoptic mfVEP appears to be a promising new tool to diagnose early glaucoma.
An Unique Type of Uveitis in IFN-g Deficient Mice
A distinct type of uveitis, predominantly granulocytic rather than monocytic in nature, develops in IFN-g deficient (GKO) mice. Su et al. (p. 4616) studied the chemokine response responsible for recruitment of inflammatory cells in this model, which is reminiscent of some acute types of human uveitis that are very destructive. They identified a unique chemokine pattern, due to the dominant Th17 and Th2 cytokine profile developed by these mice. These data have applicability to the understanding not only of uveitis, but also of inflammatory disease in general, and may help to devise interventional strategies tailored to the type of inflammation at hand.
ST2 Receptor Blockade and Susceptibility to P. aeruginosa Keratitis
Huang et al. (p. 4626) report a role for ST2, a novel negative regulator for IL-1 receptor and Toll-like receptor 4, in host resistance to P. aeruginosa keratitis. The data provide insight into biological processes involved in disease pathogenesis and show that blocking ST2 signaling by treatment with recombinant ST2 protein increased bacterial load and PMN infiltration. Th1 type cytokines such as IFN-g as well as other pro-inflammatory cytokines also were increased by blocking ST2 signaling and resulted in conversion of resistant mice to the susceptible phenotype.
Aldose Reductase Inhibition Prevents Endotoxin-Induced Uveitis in Rats
Oxidative stress-induced elevation of inflammatory markers, a hallmark of ocular inflammation commonly observed in uveitis, depends upon the activation of NF-kB and subsequent expression of inducible inflammatory marker genes. Using endotoxin induced uveitis (EIU) in Lewis rats, Yadav et al. (p. 4634) show that inhibition of aldose reductase (AR) prevents activation of NF-kB and significantly reduces inflammatory cell infiltration and increase in the levels of total protein and inflammatory markers in aqueous humor. Increase in reactive oxygen species and inflammatory marker proteins Cox-2 and iNOS in EIU are attenuated by AR inhibition. These findings suggest that AR inhibition suppresses EIU in rats by blocking the activation of NF-kB and subsequent increase in inflammatory markers. This highlights the potential of AR inhibitors in the therapy of uveitis and other ocular inflammatory disorders.
Clinically Approvable Lipopeptide Vaccines to Protect against Ocular Herpes
Safe and efficient molecularly defined vaccines are urgently needed against ocular herpes infection and disease. Bettahi et al. (p. 4643) demonstrated that immunization with a cocktail of highly immunogenic self-adjuvanting lipopeptides, bearing HSV-1 glycoprotein D (gD) T-cell determinants, elicited robust and long-term virus-specific T-cells responses (Th1 type) and decreased infection and disease in the ocular herpes mouse model. This pre-clinical study provides a first proof-of-concept that a lipopeptide approach provides a safe and molecularly defined vaccine formulation that could combat ocular infection and disease in human.
Putting T Cells to Sleep
Retinal pigment epithelial (RPE) cells are well placed in the blood-retinal barrier to potentially modulate the antigen-dependent activation of T cells in the outer retina. Gregerson et al (p. 4654) found that antigen-dependent interaction between naive CD4 T cells and RPE dissociated the antigen responses of the T cells, yielding T cells whose effector functions were suppressed and lacked significant regulatory activity. CD4 T-cell unresponsiveness to antigens was maintained following recovery from RPE and re-challenge with splenic antigen presenting cells and antigen, indicating the induction of anergy. The results show a mechanism by which RPE could promote generation of peripheral tolerance to retinal antigens.
Immune Suppression of Choroidal Neovascularization
Increasing evidence has suggested that innate immunity regulates the development of choroidal neovascularization (CNV) complicating age-related macular degeneration, yet little is known about the association of acquired immunity with CNV. Mochimaru et al. (p. 4795) describe a method for the substantial suppression of CNV by inducing cellular immunity targeting CNV-associated vascular endothelial cells. "Vaccination" of dendritic cells pulsed with a VEGFR2 epitope peptide led to induction of specific immunoresponses of CD8+ cytotoxic T lymphocytes. The present data indicate the possibility of active immunization as a novel therapeutic strategy for CNV.
Optokinetic Nystagmus for the Assessment of Visual Acuity
Wester et al. (p. 4542) evaluated optokinetic nystagmus (OKN) as an objective measurement of vision in severely visually impaired patients. Eye movements were analyzed to determine the maximum stimulus velocity (VMAX) at which subjects could maintain an OKN response. The results showed that VMAX was dependent on the visual acuity and visual field of the subject and the spatial frequency of the stimulus. This suggests that OKN results could potentially be useful in the pre- and post-operative assessment of severely visually impaired patients who are potential candidates for visual rehabilitation strategies, such as retinal prostheses, neural and stem cell transplantation, and molecular approaches.
Reflectance Changes with Focal Electrical Retinochoroidal Stimulation
Okawa et al. (p. 4777) evaluated the area of reflectance changes (RCs) in the cat retina following focal electrical suprachoroidal-transretinal stimulation (STS) using a newly developed optical imaging fundus camera. The amplitude of the electrically-evoked potentials (EEPs) was also monitored in the optic chiasm. The RCs following STS were localized to the area around the electrode. A strong correlation between the area of RCs and the amplitude of the EEPs suggests that the area of RCs reflects the activity of retinal neurons elicited by electrical stimulation. This system can be applied to evaluate the spatial resolution of artificial retinas by the STS.
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