Pathogenesis of Keratoconus: The intriguing therapeutic potential of Prolactin-inducible protein. (November 2018)

• Record Type: Journal Article
• Authors: Sharif, Rabab; Bak-Nielsen, Sashia; Hjortdal, Jesper; Karamichos, Dimitrios
• Is Part Of: Progress in retinal and eye research. Volume 67(2018:Nov.)
• Page Start: 150
• Page End: 167
• Publication Date: 2018-11
• Subjects: Human cornea -- Keratoconus -- Sex hormones -- Prolactin-induced protein -- Bodily fluids; KC Keratoconus -- PIP Prolactin-induced protein -- ECM Extracellular matrix -- SMA Smooth muscle actin -- VRQOL Vision-related quality of life -- PK Penetrating keratoplasty -- DALK Deep anterior lamellar keratoplasty -- CXL Collagen cross-linking -- RGP Rigid gas-permeable -- TIMPS Tissue inhibitors of metalloproteinases -- ROS Reactive oxygen species -- SOD Superoxide dismutase -- ICRS Intra-corneal ring segments -- TGFB1 Transforming growth factor-B1 -- SLE Systemic lupus erythematosus -- LH Luteinizing hormone -- FSH Follicle-stimulating hormone -- AR Androgen receptor -- ER Estrogen receptor -- HKC Human keratoconus cells -- HCF Human corneal fibroblasts -- CLEK Collaborative longitudinal evaluation of keratoconus; Retina -- Periodicals; Retina -- Research -- Methodology -- Periodicals; Eye -- Diseases -- Periodicals; Eye -- Periodicals; Eye Diseases -- Periodicals; Retina -- Periodicals; Rétine -- Périodiques; Rétine -- Recherche -- Méthodologie -- Périodiques; 617.7005
• DOI: 10.1016/j.preteyeres.2018.05.002
• Languages: English
• ISSNs: 1350-9462

Abstract

Abstract: Keratoconus (KC) is the most common ectatic corneal disease, with clinical findings that include discomfort, visual disturbance and possible blindness if left untreated. KC affects approximately 1:400 to 1:2000 people worldwide, including both males and females. The aetiology and onset of KC remains a puzzle and as a result, the ability to treat or reverse the disease is hampered. Sex hormones are known to play a role in the maintenance of the structure and integrity of the human cornea. Hormone levels have been reported to alter corneal thickness, curvature, and sensitivity during different times of menstrual cycle. Surprisingly, the role of sex hormones in corneal diseases and KC has been largely neglected. Prolactin-induced protein, known to be regulated by sex hormones, is a new KC biomarker that has been recently proposed. Studies herein discuss the role of sex hormones as a control mechanism for KC onset and progression and evidence supporting the view that prolactin-induced protein is an important hormonally regulated biomarker in KC is discussed. Graphical abstract: Highlights: KC is a corneal thinning disorder appearing during puberty and leads to loss of visual acuity through ectasia, opacity, and scarring. The complex, multifactorial nature of KC and lack of a suitable animal model have hampered progress in KC studies. Engineered in vitro models combined with human biological samples enables investigation of KC pathobiology. Sex hormones play a critical role in maintaining the integrity of the human cornea, and act as control mechanisms for KC onset and progression. Ongoing efforts to develop targeted treatments for KC, led to identifying the Prolactin-Induced Protein (PIP), as a biomarker for KC.