>Contents>Ocular Immune Privilege
At the beginning of this article, the argument was advanced that immune privilege in the eye is designed to limit the intraocular expression of inflammation, primarily because inflammation in this organ disrupts the visual axis and causes blindness. In addition to the extraordinary success of orthotopic corneal transplants in humans, are there other clinical situations in which ocular immune privilege might be implicated? A few possible examples are advanced below:
Sympathetic Ophthalmia
Trauma to the eye that penetrates the globe and disrupts intraocular tissues can cause sympathetic ophthalmia. Experimental evidence indicates that the uveitis that develops in the contralateral eye is directed at retinal autoantigens, implying that these powerful antigens were released by the trauma and sensitized the patient. Yet, only a small minority of individuals suffering such an ocular wound actually develop sympathetic ophthalmia. Perhaps a reason why more patients don’t develop this autoimmune complication is that antigen released by the trauma induces ACAID. If true, this is an example where the physiologic existence of immune privilege proves advantageous to the eye.
Recurrent Herpes Uveitis
Clearance of the herpes simplex virus from infected tissue (such as in herpes labialis) depends upon immunity mediated by CD4+ T cells of the delayed hypersensitivity type. In experimental animals, ACAID can be induced to HSV antigens, i.e. the animals fail to acquire HSV-specific delayed hypersensitivity. Transient inhibition of CD4+ T-cell immunity early in ocular herpes infection markedly reduces the incidence of stromal keratitis in mice, indicating that ocular immune privilege protects vision. A similar protective effect of ACAID might also occur in humans. However, some patients recover from an acute ocular herpes infection only to develop recurrent herpes uveitis during which live virus can be recovered from the afflicted eye. The possibility exists that in these subjects ACAID may persist indefinitely and thereby prevent immune elimination of virus from ocular tissues, thus promoting persistent, recurrent infections. If true, this would be an example where the existence of immune privilege has a disadvantageous outcome.
It remains to be determined experimentally whether innate and adaptive immune privilege, or its loss, plays a role in eye diseases. One can imagine that the incidence and severity of acute anterior uveitis might be reduced because of the existence of immune privilege, and one can speculate that rapid growth of spontaneous intraocular tumors might depend upon the integrity of immune privilege. Considering the power of ocular privilege to suppress innate immune effectors, the possibility even exists that immune privilege may have a role in the pathogenesis of diseases with inflammatory components – such as age-related macular degeneration, optic neuropathy of glaucoma, and even diabetic retinopathy. Working out the details of the molecular basis for ocular immune privilege promises a cornucopia of new approaches to the many multifactorial diseases that are currently untreatable and that cause significant loss of sight.
The Eye's Dilemma
Immune Privilege
Anterior Chamber of the Eye as an Immune- Privileged Site
Inflammation of Relation to Innate and Adaptive Immune Responses
Ocular Factors That Promote Immune Tolerance of Eye-Derived Antigens
Factors That Modify Expression of Ocular Adaptive Immunity
Innate Immune Privilege in the Eye
Factors That Modify Expression of Innate Ocular Immunity
Clinical Meaning of Ocular Immune Privilege
Selected Reading
Biography
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