Etiology of equine recurrent uveitis (ERU): Autoimmune disease or intraocular leptospiral infection?

Abstract

The literature concerning the etiology of equine recurrent uveitis (ERU) seems to be confusing for decades, as it is reported on one hand to be an autoimmune disease because there are autoimmune reactions detectable, and on the other hand there have been repeated proves of an intraocular leptospiral infection. With vitrecomy becoming established in horses suffering from ERU, it is the first time that vitreous samples from diseased eyes can routinely be taken in great numbers. Vitreous samples, obtained from eyes suffering from ERU during vitrectomy, can be used for studies concerning humoral and cellular autoimmune phenomenons aswell as for microbiological examinations. These vitreous samples may contribute to understand the etiology and the pathogenesis of ERU. Besides serum samples from 724 horses suffering from ERU and from 132 sound horses, undiluted and sterile vitreous samples could be taken during 1998-2001 from 426 eyes suffering from ERU. Controls were vitreous samples from 54 sound eyes. All samples (vitreous and serum) were tested for antibodies against leptospires using microagglutination test (MAT). For calculation of the Goldman-Witmer-Coefficient (C), electrophoresis has been performed in 36 paired vitreous and serum samples. Vitreous samples from 41 ophthalmoscopically sound eyes and from 358 eyes suffering from ERU were used for leptospiral culturing. Additionally, 55 of the vitreous samples from ERU-eyes were tested with polymerase chain reaction (PCR) for detection of leptospiral DNA. Vitreous samples from 6 eyes could be reexamined in different intervals after surgery and tested for antibodies against leptospires with MAT. From the eyes which underwent vitrectomy, in 150 the course of the disease could be pursued for an average of 2,7 years. In serum samples, there was only minor and not significant difference in occurrence and level of antibodies against leptospires comparing sound horses and horses suffering from ERU. In 3/54 (6%) of vitreous samples from sound eyes and in 382/426 (90%) of vitreous samples from eyes suffering from ERU MAT could detect antibodies. Calculation of the Goldman-Witmer- Coefficient proved intraocular antibody production in 34/36 (94%) eyes (C > 8). Positive culture results were observed in 189/358 (53%) vitreous samples from eyes suffering from ERU and in none of 41 vitreous samples from sound eyes. Positive culture results were seen in vitreous samples from eyes which had a history of ERU of only a few weeks aswell as in samples from eyes with a history of ERU for several years. In 18/189 (9,5%) of serum samples corresponding to vitreous samples with positive culture results, MAT could not detect antibodies against leptospires any more. PCR showed leptospiral DNA in 39/55 (71%) of vitreous samples from ERU-eyes. Re-examined vitreous samples showed decreasing antibody titers with increasing intervals after vitrectomy and one year after surgery MAT fail-ed detecting antibodies. Uveitis ceased completely in 1471150 (98%) eyes after vitrectomy. The results show clearly that in horses suffering from ERU an intraocular leptospiral infection is present. The intraocular infection aswell as recurrent uveitic attacks stop after vitrectomy. As only the vitreous, but no intraocular antigens from retina or other intraocular structures are removed, and as nearly 100% of the eyes in which surgery had been performed have no further uveitic attacks, autoimmune reactions in horses suffering from ERU must be caused by the intraocular persistent leptospiral infection. Thus, ERU is not an "autoimmune disease", but an intraocular persisting leptospiral infection, which causes infection-associated autoimmune phenomenons until the intraocular leptospirosis is eliminated by vitrectomy.