Review: Uveitis and Immunosuppressive Drugs

Abstract

Uveitis, inflammation of the eye, is a common occurring disease resulting from a wide variety of traumatic and immunogenic insults and, in most cases, can be treated successfully by corticosteroids. However, corticosteroids have severe side effects. Alternative therapy is using nonsteroidal anti-inflammatory agents like indomethecin, diclofenac and flurbiprofen. The uveitic cases are prominent in the third world countries, and many of the patients are not responsive or become refractory to steroidal or nonsteroidal therapy. Therefore, there is another class of compounds "immunosuppressive drugs" found to be successful in treating uveitis. These include cyclosporin A, tacrolimus, and sirolimus. However, being immunosuppressive they also have side effects. Therefore, the effective therapy with lower side effects is the treatment with combination of these drugs in lower dosages. Cyclosporin A plus sirolimus or tacrolimus in threshold doses alleviate signs of uveitis with lower incidence of side effects.

Inhibition of Apoptosis Through Localized Delivery of Rapamycin-Loaded Nanoparticles Prevented Neointimal Hyperplasia and Reendothelialized Injured Artery

“…32 Our approach was to protect VSMCs from undergoing apoptosis shortly after vascular injury and to prevent their proliferation. Thus, rapamycin seems to be the right choice of drug, not only because of its antiproliferative and antiinflammatory activities 33 but also because it has been shown to downregulate the proapoptotic genes in VSMCs. 8 Immunohistochemical analysis of the arterial sections collected at 1 hour after infusion of rapamycin-loaded NPs demonstrated inhibition of apoptosis in the treated artery ( Figures 5A and 5B), thus supporting the above mechanism of rapamycin.…”

Tolerability and Pharmacokinetics of Intravitreal Sirolimus

“…1,2 Sirolimus, a potent immunosuppressant, is occasionally administered orally for refractory uveitis, although systemic use is also associated with multiple side effects. [2][3][4] Intravitreal (IVT) administration offers an alternative where drugs can be delivered to the retina/choroid while limiting systemic adverse effects.…”

“…5 Sirolimus arrests cell-cycle progression by direct interaction with 2 intracellular proteins, specifically the immunophilin FK 1 Pharmaceutical and Preclinical Development Department, Santen Incorporated, Emeryville, California. 2 Santen Pharmaceutical Co., Ltd., Ikoma-shi, Nara, Japan.…”

Intravitreal implantation of the biodegradable cyclosporin A drug delivery system for experimental chronic uveitis

“…Approximately 4-10% of blindness in China can be attributed to uveitis [11]. Cyclosporin A (CsA) has been widely and effectively used for the treatment of various forms of chronic uveitis [4,9,10]. However, poor penetration of topical CsA into the eye and serious systemic toxicity produced by oral administration require a new approach to overcome the hurdles of blood-ocular block and low bioavailability of CsA.…”