Hellenic Army Medical Corps, Thessaloniki, Greece.
Ophthalmica Eye Institute, Vas Olgas 196 and Ploutonos 27, 54655, Thessaloniki, Greece.
Adv Ther. 2019 Sep;36(9):2205-2222. doi: 10.1007/s12325-019-01026-0. Epub 2019 Jul 30.
Keratoconus (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.
PubMed, 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.
A 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.
The 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.
圆锥角膜（KC）是一种复杂的、遗传异质性的多因素退行性疾病，其特征为角膜扩张和变薄。在普通人群中，其发病率约为 1/2000-1/50000。KC 与中高度近视和不规则散光有关，导致严重的视力损害。KC 的结构异常主要与角膜胶原的弱化有关。了解这些异常对于有效管理疾病至关重要，例如使用角膜交联（CXL）。本文批判性地回顾了与 KC 病理生理学相关的蛋白，特别强调了与 CXL 相关的胶原特性。
在 2006 年 1 月至 2018 年 6 月期间，通过 PubMed、MEDLINE、Google Scholar 和 GeneCards 数据库以“圆锥角膜”、“危险因素”、“遗传学”、“基因”、“遗传关联”、“蛋白”、“胶原”和“角膜”等关键词组合，筛选发表在英文文献中的相关文章。共检索到 272 篇文章，进行了回顾和选择，更注重最近发表的证据。根据综述文献，尝试列出与 KC 相关的基因及其蛋白产物的上调和下调，并描述 CXL 涉及的机制。
共有 117 种蛋白和蛋白类被认为与 KC 的发病机制和病理生理学有关。根据其基因编码、生物化学和代谢控制，将这些蛋白分类列在七个不同的表格中。
KC 的发病机制和病理生理学仍然很神秘。新出现的证据提高了我们对 KC 分子特征的理解，这可能进一步提高 CXL 治疗的成功率。
