Retinal Immunology

Thurau S, Wildner G Oral tolerance for treating uveitis - New hope for an old immunological mechanism. Prog Retin Eye Res 2002 21 577-589. 

There are many retinal diseases for which currently no effective treatment exists. The potential usefulness of rednal transplantation as a heatment option can be explored once the knowledge of the parameters determining the immunologic rejection of allogeneic retinal hansplant and biologic mechanisms of cells transplanted into subretinal space are better known. 

The molecular weight of halorhodopsin is estimated from SDS gel patterns of halo-opsin labeled with H-labeled retinal [94] and of purified halorhodopsin [95,96], and it appears to be slightly lower than that of bacteriorhodopsin, i.e., about 25000. Differences in the cleavage patterns from limited proteolysis, as well as lack of immunological crossreactivity, suggest that halo-opsin and bacterio-opsin are very different proteins, however [95]. 

Jiang LQ, Jorquera M, Streilein JW (1993) Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts. Invest Ophthalmol Vis Sci 34 3347-3354. 

Liversidge JM, Sewell HF, Forrester JV (1990) Interaction between Lymphocytes and cells of the blood-retina barrier Mechanisms of T lympohocyte adhesion to human retinal capillary endothelial cells and RPE cells in vitro. Immunology 71 390-396. 

In a study of compassionate use of intravenous cidofovir in AIDS patients with CMV retinitis, iritis developed in 21 of 51 individuals (7). The appearance of this inflammatory process did not fit the characteristics of the vitritis associated with immune reconstitution, or with HIV-induced vitritis. The high rate in this cohort (compared with a 5-7% incidence in randomized trials) was associated with severe CMV retinitis, and the authors suggested that breakdown of the blood-ocular barrier in these patients may promote higher intraocular concentrations of cidofovir and thus enhance local toxicity. Previous correlations of prior use of HIV protease inhibitors with iritis were not confirmed in this study, although patients with iritis had better immunological and virological status than those without the disease. 

For its protection, the retina is physiologically and immunologically segregated from the rest of the body by the blood retinal barrier formed by tight junctions between vascular endothelial cells and RPE cells. Only small molecules can cross this barrier, making it difficult for many drugs to reach ocular tissue. In addition, intraocular tissue is an immune privileged site. This protects the ocular tissue from the innocent bystander effect of inflammation. 

The mechanism of action of the immunological and anti-inflammatory effects of antimalarials include inhibition of phospholipase A, inhibition of platelet aggregation, a range of lysosomal effects (e.g., an increase in pH, membrane stabilization, and inhibition of release and activity of lysosomal enzymes), inhibition of phagocytosis, an increase in intracellular pH in cytoplasmic vacuoles leading to decreased stimulation of autoimmune CD4 T cells, decreased cytokine release from lymphocytes and stimulated monocytes, inhibition of immune complex formation, and antioxidant activity. In patients with porphyria cutanea tarda, chloroquine and hydroxychloroquine bind to porphyrins and/or iron to facilitate their hepatic clearance. The ability to bind to melanin and other pigments may contribute to the retinal toxicity seen occasionally when anti-malarial agents are used. 

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