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| EDITORIAL |
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| Year : 1999 | Volume
: 47
| Issue : 2 | Page : 62-63 |
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Do the experimental models represent human uveitis or retinal autoimmunity?
Narsing A Rao
Dohney Eye Institute, 1450 San Pablo St., Los Angeles, CA 90033, India
Correspondence Address:
Narsing A Rao
Dohney Eye Institute, 1450 San Pablo St., Los Angeles, CA 90033
India
 Source of Support: None, Conflict of Interest: None  | Check |
How to cite this article:
Rao NA. Do the experimental models represent human uveitis or retinal autoimmunity?. Indian J Ophthalmol 1999;47:62-3 |
Much of what is known about the interactions of the immune system has been gleaned from the study of animal models of autoimmune diseases. This information has aided investigators in understanding some of the very complex pathways that may be involved in human autoimmune diseases as well. Individuals both with and without uveitis or other related intraocular inflammations have been found to have circulating T-cells that react in-vitro to retinal antigens. To study the mechanism(s) by which these autoantigens may initiate uveitis in humans, investigators have developed a number of animal models which utilize retinal antigens to induce inflammation. These retinal autoantigens include S-antigen, interphotoreceptor retinoid binding protein, rhodopsin, phosducin, and recoverin.
In this issue of the journal, Singh et al[1] review some recent advances in the field of uveitis gathered from studies on animal models of intraocular inflammations. One of the most commonly used experimental models in such research utilizes S-antigen. The inflammation produced in these animals is characterized by an initial retinal vasculitis, which subsequently extends into the photoreceptor layer, ultimately leading to the total destruction of the latter from oxidative stress.[2] Although several investigations use an S-antigen model to explore the mysteries inherent in uveitis, it is important to recognize that such models represent retinal autoimmunity.
It is clear that once activated T-cells specific for S-antigen reach the retinal tissue, there must be a way that the antigen can be locally presented to the T-cells. Recent in-vivo and in-vitro studies on chimeric animals indicate a role for bone-marrow derived retinal microglial cells as the putative local antigen presenting cells.[3],[4] Such local antigen presentation causes an influx of other cells to the site due to the liberation of cytokines and chemotactic factors. Some of these inflammatory mediators are produced by T-cells; others are elaborated by the retinal cells. The recruitment of effector cells to the site results in the subsequent release of proteolytic enzymes and reactive free radicals such as superoxide and nitric oxide, which then cause further damage to the retinal tissue.[5]
As stated by Singh and colleagues,[1] molecular mimicry is a potential mechanism by which autoimmune uveitis may be induced in humans. If indeed retinal autoantigens have the potential to cause such devastation in the eye, it is equally evident that regulatory mechanisms are in place that protect the retina from such damage. It has been demonstrated that Mueller cells have an inhibitory influence on lymphocyte proliferation. The retinal pigment epithelium has also been demonstrated to produce TGF-β and a retinal protective peptide (RPP), both of which are immunosuppressive factors.[6] Moreover, vitreous and subretinal space offer immune privilege. Therefore, although the retina is able to mount an autoimmune response by virtue of its disease-causing autoantigens it also has armaments to protect itself against damage.
In conclusion, the S-antigen induced uveitis model primarily represents retinal autoimmunity. In spite of the fact that T-cells reactive to retinal antigens and capable of causing disease are normally present in humans, it is clear that the immune system can cope with these autoreactive cells since not every individual presents with retinal autoimmunity or uveitis. To fully understand the complex workings of the ocular immune system and the immune response in general, the mechanisms(s) by which this threat of autoimmune disease is kept in check, as well as those that play a role in the induction of autoimmunity, must be completely elucidated. Needless to say, this presents a challenging, even a Herculean task for those involved in the fields of both applied immunology and ophthalmology.
| References | |  |
| 1. | Singh VK, Biswas S, Raig, Agarwal SS. Immunomodulation in human and experiemental uveiits: recent adances Indian J Ophthalmol 1999;47:65-77.  |
| 2. | Rao NA. Role of oxygen free radicals in retinal damage associated with experimental uveitis. Trans Am Ophthalmol Soc 1990;88:797-850. [ PUBMED] [ FULLTEXT] |
| 3. | Ishimoto S, Zhang J, Gullapalli VK, Pararajasegaram G, Rao NA. Antigen-presenting cells in experimental autoimmune uveoretinitis. Exp Eye Res 1998;67:539-48. [ PUBMED] [ FULLTEXT] |
| 4. | Matsubara T, Pararajasegaram G, Wu GS, Rao NA. Retinal microglia differentially express phenotypic markers of antigen-presenting cells in vitro. Invest Ophthalmol Vis Sci (In press). |
| 5. | Wu GS, Zhang J, Rao NA. Peroxynitrite and oxidative damage in experimental autoimmune uveitis. Invest Ophthalmol Vis Sci 1997;38:1333-39. [ PUBMED] |
| 6. | Wu GS, Rao NA. Activation of NADPH-oxidase by docosahexaenic acid hydroperoxide and its inhibition by novel retinal pigment epithelial protein. Invest Ophthalmol Vis Sci 1999;40:831-39. [ PUBMED] |
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