Aquaporin 11, a regulator of water efflux at retinal Müller glial cell surface decreases concomitant with immune-mediated gliosis.

BACKGROUND: Müller glial cells are important regulators of physiological function of retina. In a model disease of retinal inflammation and spontaneous recurrent uveitis in horses (ERU), we could show that retinal Müller glial cells significantly change potassium and water channel protein expression during autoimmune pathogenesis. The most significantly changed channel protein in neuroinflammatory ERU was aquaporin 11 (AQP11). Aquaporins (AQP, 13 members) are important regulators of water and small solute transport through membranes. AQP11 is an unorthodox member of this family and was assigned to a third group of AQPs because of its difference in amino acid sequence (conserved sequence is only 11 %) and especially its largely unknown function. METHODS: In order to gain insight into the distribution, localization, and function of AQP11 in the retina, we first developed a novel monoclonal antibody for AQP11 enabling quantification, localization, and functional studies. RESULTS: In the horse retina, AQP11 was exclusively expressed at Müller glial cell membranes. In uveitic condition, AQP11 disappeared from gliotic Müller cells concomitant with glutamine synthase. Since function of AQP11 is still under debate, we assessed the impact of AQP11 channel on cell volume regulation of primary Müller glial cells under different osmotic conditions. We conclude a concomitant role for AQP11 with AQP4 in water efflux from these glial cells, which is disturbed in ERU. This could probably contribute to swelling and subsequent severe complication of retinal edema through impaired intracellular fluid regulation. CONCLUSIONS: Therefore, AQP11 is important for physiological Müller glia function and the expression pattern and function of this water channel seems to have distinct functions in central nervous system. The significant reduction in neuroinflammation points to a crucial role in pathogenesis of autoimmune uveitis.

The uveitogenic potential of retinal S-antigen in horses.

PURPOSE: To investigate the uveitogenic potential of retinal S-antigen (S-Ag) in horses. METHODS: Horses were immunized subcutaneously with S-Ag or BSA as control antigen, emulsified in complete Freund's adjuvant. Simultaneously, Bordetella pertussis was given intravenously. Antigen specific T- and B-cell responses were analyzed in a 3-day interval. Disease development was judged clinically and histopathologically. Two identical booster immunizations were given every 4 weeks to test induction of recurrences. RESULTS: T- and B-cell responses specific for S-Ag were observed in all immunized horses but were absent in control animals. However, uveitis developed in only one of five animals. Reimmunization with S-Ag did not lead to a uveitic relapse in this horse. All other horses of the S-Ag- and BSA-treated groups neither showed any signs of uveitis, nor had inflammatory infiltrates of the inner eye. CONCLUSIONS: In contrast to interphotoreceptor retinoid-binding protein (IRBP), S-Ag is a weak autoantigen in horses. Even though S-Ag immunization leads to the activation of autoreactive T- and B-cells, infiltration of the inner eye and induction of uveitis are controlled in most horses.

Uveitis in horses induced by interphotoreceptor retinoid-binding protein is similar to the spontaneous disease.

Equine recurrent uveitis (ERU) is an inflammatory eye disease with high similarity to uveitis in man. It is the only spontaneous animal model for uveitis and the most frequent eye disease in horses affecting up to 10% of the population. To further investigate the pathophysiology of ERU we now report the establishment of an inducible uveitis model in horses. An ERU-like disease was elicited in seven out of seven horses by injection of interphotoreceptor retinoid-binding protein (IRBP) in complete Freund's adjuvant. Control horses did not develop uveitis. The disease model is characterized by a highly reproducible disease course and recurrent episodes with an identical time course elicited in all horses by repeated IRBP injections. The histology revealed the formation of lymphoid follicle-like structures in the eyes and an intraocular infiltration dominated by CD3(+) lymphocytes, morphological patterns typical for the spontaneous disease. Antigen-specific T cell proliferation of PBL was monitored prior to clinical uveitis and during disease episodes. An initial T cell response to IRBP-derived peptides was followed by epitope spreading to S-antigen-derived peptides in response to subsequent immunizations. Thus, horse experimental uveitis represents a valuable disease model for comparative studies with the spontaneous disease and the investigation of immunomodulatory therapeutic approaches after onset of the disease.

Llama dermatology.

The purpose of this article is to add information to the many dermatologic topics initially discussed in the 1989 issue on llama medicine (normal anatomy; bacterial, fungal, ectoparasitic, immune-mediated, and zinc-responsive disease) and make mention of newly recognized diseases. Since 1989, it appears that one of the most common and perplexing groups of dermatoses seen at Colorado State University are hyperkeratotic/inflammatory dermatoses. These remain poorly understood. Idiopathic hyperkeratosis (zinc-responsive dermatosis) may be a true zinc deficiency or a keratinizing disorder responsive to supraphysiologic dosages of zinc supplementation. Idiopathic nasal/perioral hyperkeratotic/ inflammatory dermatosis (munge) and idiopathic necrolytic/neutrophilic/hyperkeratotic dermatosis bear clinical, histologic, and therapeutic similarities, and may be subsets of the same disease. Further studies (e.g., looking for metabolic derangements) are necessary to better answer these questions.

Acupuncture for immune-mediated disorders. Literature review and clinical applications.

Acupuncture activates the defense systems. It influences specific and nonspecific cellular and humoral immunities; activates cell proliferation, including blood, reticuloendothelial, and traumatized cells; and activates leucocytosis, microbicidal activity, antibodies, globulin, complement, and interferon. It modulates hypothalamic-pituitary control of the autonomic and neuroendocrine systems, especially microcirculation, response of smooth and striated muscle, and local and general thermoregulation. Immunostimulant points include LI-4, LI-11, ST-36, GB-39, SP-6, GV-14, BL-11, BL-20, BL-23, BL-24, BL-25, BL-26, BL-27, BL-28, and CV-12. Some, such as BL-47, are immunosuppressive. Antifebrile points include GV-14 and ST-36. Reactive reflex SHU points, MU points, and earpoints are useful in organic diseases. In immunomediated diseases, some or all of these points can be used with other points, especially local points and points of the major symptoms or points of the affected body part, area, function, or organ. Applications of acupuncture include treatment of inflammation and trauma; stimulation of tissue healing in burns, ulcers, indolent wounds, ischemia, necrosis, and gangrene; infections; postinfection sequelae; fever; autoimmune disease; allergies; anaphylaxis and shock; and treatment or prevention of side effects from cytotoxic chemotherapy and ionizing radiation. Acupuncture therapy may inhibit neoplastic cells. Examples of acupuncture use in immunomediated conditions in small animals are given.