The Proteins of Keratoconus: a Literature Review Exploring Their Contribution to the Pathophysiology of the Disease

Abstract

IntroductionKeratoconus (KC) is a complex, genetically heterogeneous multifactorial degenerative disorder characterized by corneal ectasia and thinning. Its incidence is approximately 1/2000–1/50,000 in the general population. KC is associated with moderate to high myopia and irregular astigmatism, resulting in severe visual impairment. KC structural abnormalities primarily relate to the weakening of the corneal collagen. Their understanding is crucial and could contribute to effective management of the disease, such as with the aid of corneal cross-linking (CXL). The present article critically reviews the proteins involved in the pathophysiology of KC, with particular emphasis on the characteristics of collagen that pertain to CXL.MethodsPubMed, MEDLINE, Google Scholar and GeneCards databases were screened for relevant articles published in English between January 2006 and June 2018. Keyword combinations of the words “keratoconus,” “risk factor(s),” “genetics,” “genes,” “genetic association(s),” “proteins”, “collagen” and “cornea’’ were used. In total, 272 articles were retrieved, reviewed and selected, with greater weight placed on more recently published evidence. Based on the reviewed literature, an attempt was made to tabulate the up- and down-regulation of genes involved in KC and their protein products and to delineate the mechanisms involved in CXL.ResultsA total of 117 proteins and protein classes have been implicated in the pathogenesis and pathophysiology of KC. These have been tabulated in seven distinct tables according to their gene coding, their biochemistry and their metabolic control.ConclusionThe pathogenesis and pathophysiology of KC remain enigmatic. Emerging evidence has improved our understanding of the molecular characteristics of KC and could further improve the success rate of CXL therapies.

Comparison of Corneal Biomechanical Properties between Post-LASIK Ectasia and Primary Keratoconus

“…However, whether there is a difference in corneal biomechanics between post-LASIK ectasia and primary keratoconus is unknown. A large number of proteins and protein classes are involved in the development of keratoconus [ 14 ], and these pathological changes may lead to a change in corneal biomechanics. The current study aimed to investigate the differences in biomechanical properties between post-LASIK ectasia and primary keratoconus.…”

Molecular Genetics of Keratoconus: Clinical Implications

“…A review of published studies on proteins, collagen and risk factors of keratoconus between January 2016 and June 2018 has revealed altered regulations in more than 30 proteins and their genes. They belong to protein families including degradative enzymes, cellular proteases, and collagens [121]. Up-and downregulations of hosts of proteins in corneal epithelium and stroma have been reported in keratoconus, especially different types of collagen and matrix metalloproteinases.…”

“…Expression studies also showed downregulation of many collagen types and subtypes in keratoconus, including COL8A1, COL8A2, COL12A1, COL13A1, COL6A2, COL15A1, and COL18A1 [125][126][127]. They may be considered for use as biomarkers in keratoconus, [121] but practical protocols and validations are still to be established.…”

Role of Tryptophan-Metabolizing Microbiota On Diarrhea Mice Caused by Folium sennae Extracts

“…The target prediction for the main active compounds screened out by the above step was performed using the PharmMapper server (http://www.lilabecust.cn/pharmmapper/) with the "Homo sapiens" species setting, and the gene targets of Folium sennae were selected. After searching Genecard datasets (https://www.genecards.org/) using keywords "diarrhea" [21], all gene targets of diarrhea disease were enrolled. In the next step, the two datasets of gene targets are intersected to identify gene targets of Folium sennae for diarrhea disease.…”