Anterior chamber associated immune deviation to cytosolic neural antigens avoids self-reactivity after optic nerve injury and polarizes the retinal environment to an anti-inflammatory profile.

It has been hypothesized that anterior chamber-associated immune deviation (ACAID) to neural antigens induced prior to central nervous system injury can inhibit self-reactivity and lessen secondary degeneration. This work evaluated the effect of ACAID induced to three neural tissue-derived extracts (whole extract, cytosolic extract, CE; or organelle-membrane extract) prior to optic nerve injury on retinal ganglion cell (RGC) survival. The results show that only ACAID to the CE increased RGC survival at 7 and14 days post-injury (dpi). This effect was achieved by retinal polarization towards an anti-inflammatory profile, driven by regulatory T cells and M2-type macrophages at 7 dpi.

ACAID as a potential therapeutic approach to modulate inflammation in neurodegenerative diseases.

The progressive loss of neurons and inflammation characterizes neurodegenerative diseases. Although the etiology, progression and outcome of different neurodegenerative diseases are varied, they share chronic inflammation maintained largely by central nervous system (CNS)-derived antigens recognized by T cells. Inflammation can be beneficial by recruiting immune cells to kill pathogens or to clear cell debris resulting from the primary insult. However, chronic inflammation exacerbates and perpetuates tissue damage. An increasing number of therapies that attempt to modulate neuroinflammation have been developed. However, so far none has succeeded in decreasing the secondary damage associated with chronic inflammation. A potential strategy to modulate the immune system is related to the induction of tolerance to CNS antigens. In this line, it is our hypothesis that this could be accomplished by using anterior chamber associated immune deviation (ACAID) as a strategy. Thus, we review current knowledge regarding some neurodegenerative diseases and the associated immune response that causes inflammation. In addition, we discuss further our hypothesis of the possible usefulness of ACAID as a therapeutic strategy to ameliorate damage to the CNS.

Intraocular inflammation associated with ocular toxoplasmosis: relationships at initial examination.

PURPOSE: To describe characteristics of intraocular inflammation in eyes with active ocular toxoplasmosis and to identify relationships between signs of inflammation, complications (including elevated intraocular pressure [IOP]), other disease features, and host characteristics. DESIGN: Multicenter, retrospective, cross-sectional study. METHODS: We reviewed the medical records of 210 patients with toxoplasmic retinochoroiditis at seven international sites (North America, South America, and Europe) for information from the first examination at each site during which patients had active retinal lesions. Signs of inflammation included anterior chamber (AC) cells and flare and vitreous humor cells and haze. Retinal lesion characteristics included size (< or =1 disc area [DA] or >1 DA) and presence or absence of macular involvement. RESULTS: AC cells and flare were related to vitreous inflammatory reactions (P < or = .041). One or more signs of increased inflammation were related to the following factors: older patient age, larger retinal lesions, and extramacular location. In 30% of involved eyes, there was evidence of elevated IOP (despite use of glaucoma medications by some patients); other complications were uncommon. IOP of more than 21 mm Hg was associated with both increased AC cells and elevated flare (both P < or = .001) and with macular involvement (P = .009). Inflammation seemed to be more severe among patients in Brazil than among those at other sites. CONCLUSIONS: There is substantial variation between patients in the severity of intraocular inflammation associated with ocular toxoplasmosis, attributable to multiple host- and disease-related factors. Results suggest that disease characteristics also vary in different areas of the world. Elevated IOP at initial examination reflects the severity of inflammation.