Progress in the genetics of uveitis

Abstract

Uveitis is the most common form of intraocular inflammatory disease and is a significant cause of visual impairment worldwide. Aetiologically, uveitis can also be classified into infectious uveitis and non-infectious uveitis. The common non-infectious forms of uveitis include acute anterior uveitis (AAU), Behçet’s disease (BD), Vogt-Koyanagi-Harada (VKH) disease, birdshot chorioretinopathy (BSCR), sarcoid uveitis. In addition, a few monogenic autoinflammatory disorders can also cause uveitis, such as Blau Syndrome and haploinsufficiency of A20 (HA20). Although the exact pathogenesis of non-infectious uveitis is still unclear, it is well-recognised that it involves both genetic and environmental risk factors. A hallmark of uveitis is its strong associations with human leucocyte antigens (HLA). For examples, AAU, BD and BSCR are strongly associated with HLA-B27, HLA-B51, and HLA-A29, respectively. In uveitis studies, multiple GWAS have successfully been conducted and led to identification of novel susceptibility loci, for example, IL23R has been identified in BD, VKH and AAU. In this review, we summarize the latest progress on the genetic associations of both HLA and non-HLA genes with major forms of uveitis, including AAU, BD, VKH, BSCR, sarcoid uveitis, Blau Syndrome and HA20, and potential future research directions.

Long-Acting Fluocinolone Acetonide Intravitreal Implant for Recurrent Bilateral Non-Infectious Posterior Uveitis

“…The most common cause of intraocular inflammation is idiopathic, which is responsible for at least 50% of all uveitis cases. 2 , 3 NIPU is the third most common type of idiopathic intraocular inflammation in the United States, accounting for 10% of all cases in adults with severe vision loss without proper diagnosis and management. 1 , 2 , 6 , 8 , 9 NIPU classically presents as periodic flares of inflammation leading to worsening non-reversible vision loss over time.…”

“… 1 , 3 Mutations in genes encoding these MHC molecules predisposes patients to autoimmune and exaggerated immune responses implicated in the pathogenesis of NIU. 1 , 3 The IL-23R gene produces the IL-23R which is found on the Th17 cell surface and is the second most common susceptibility gene for NIU. 1 , 3 This receptor, when bound to its IL-23 ligand, plays an integral role in Th17 homeostasis, differentiation to pathological Th17 cells, and production of inflammatory cytokines (IL-17, IL-6, interferon- γ) which are observed in certain non-infectious uveitic diseases such as Adamantiades–Behçet’s disease, Vogt-Koyanagi-Harada disease, and sarcoidosis.…”

“… 1 , 3 This receptor, when bound to its IL-23 ligand, plays an integral role in Th17 homeostasis, differentiation to pathological Th17 cells, and production of inflammatory cytokines (IL-17, IL-6, interferon- γ) which are observed in certain non-infectious uveitic diseases such as Adamantiades–Behçet’s disease, Vogt-Koyanagi-Harada disease, and sarcoidosis. 1 , 3 …”

“… 2 Posterior uveitis is the second most common uveitis and primarily involves the choroid (choroiditis), retina (retinitis), or both (chorioretinitis and retinochoroiditis); it can also involve the optic nerve (neuroretinitis). 2 , 3 Inflammation’s foci can be either single, multiple, or diffuse. 2 In panuveitis, all structures of the uveal tract are inflamed.…”

“…Uveitis is inflammation of the vascular layer connecting the sclera and neurosensory retina; the uveal tract includes the iris, ciliary body, and choroid. [1][2][3] Anterior uveitis is most common and primarily involves inflammation of the iris (iritis), pars plicata of the ciliary body (anterior cyclitis), or both (iridocyclitis). 2,3 Intermediate uveitis primarily involves the vitreous (vitritis).…”