Keratoconus: an inflammatory disorder?

Abstract

Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

Variants in SKP1, PROB1, and IL17B genes at keratoconus 5q31.1–q35.3 susceptibility locus identified by whole-exome sequencing

“…Still, there are several reports supporting the notion of a role of inflammation in the thinning and weakening of the corneal tissue in KTCN. 34,35 In 2013, we identified several variants in genes encoded inflammatory molecules, IL1A and IL1B, in a KTCN family, but we observed a random distribution of them between KTCN and normal individuals. On the other hand, in all KTCN patients, we found a c.214+242C4T variant in the IL1RN gene, whose protein product modulates the effect of IL-1.…”

Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas

“…3 Recently, it was suggested that KTCN could be a quasiinflammatory condition. 4 However, the exact causes of this disease are not well characterized, and its complexity and heterogeneity make it difficult to discover the factors that unambiguously trigger the KTCN phenotype.…”

Influence of the Corneal Collagen Cross-linking on Levels of Il- 1b, Il-6, Il-10 and MMP-2 in the Tear film of Patients with Keratoconus.

“…It is a stromal dystrophy, classified as a progressive, noninflamatory state characterized by lesions leading to decrease in thickness of central and pericentral cornea and consequent hallmark "cone-shaped" form [2]. KC is characterized by a distortion of the biochemical composition of certain corneal layers: a deficit of collagen type VII, XII and VI in the epithelium and of type I, III, V, VI and XII in the stroma.…”