ophthalmologyОфтальмологияOphthalmology in Russia1816-50952500-0845Ophthalmology10.18008/1816-5095-2015-1-4-7ophthalmology-218Research ArticleОБЗОРЫREVIEWSКератоконус как проявление соединительнотканных дисплазийKeratoconus as a manifestation of connective tissue dysplasiaБикбовМ. М.BikbovM. M.СурковаВ. К.SurkovaV. K.ОганисянК. Х.OganisyanK. Kh.oko-ufa@yandex.ruГосударственное бюджетное учреждение «Уфимский научно-исследовательский институт глазных болезней Академии наук Республики Башкортостан», ул. Пушкина, д. 90, Уфа, 450008, РоссияРоссияUfa Eye Research Institute of Academy of Sciences of the Republic of Bashkortostan, 90, Pushkina Str. Ufa, Russia, 450008Russian Federation20153103201512147Copyright © Бикбов М.М., Суркова В.К., Оганисян К.Х., 20152015Бикбов М.М., Суркова В.К., Оганисян К.Х.Bikbov M.M., Surkova V.K., Oganisyan K.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.ophthalmojournal.com/opht/article/view/218

Частое сочетание кератоконуса и системных дисплазий соединительной ткани указывает на возможную этиопатогенетическую общность этих заболеваний. Системные дисплазии соединительной ткани характеризуются снижением содержания отдельных типов коллагена, нарушением их соотношения, изменениями темпов синтеза и сборки коллагена, синтезом незрелого коллагена, нарушением структуры коллагеновых волокон, дефектом синтеза коллагена III типа, дефицитом пептидаз и нарушением соотношения коллагена и проколлагена в сторону увеличения последнего. Последнее объясняет нарастание доли незрелого коллагена в тканях и органах и, как следствие, системную врожденную неполноценность соединительной ткани. Все это ведет к изменению биомеханических свойств органов и тканей, основу которых составляют коллагеновые волокна. Строма роговицы представлена в основном коллагеновыми волокнами, погруженными в гликопротеиновый матрикс, поэтому количественные и качественные изменения, происходящие при дисплазиях соединительной ткани, изменяют биомеханические свойства роговицы. Изменение ориентации коллагеновых фибрилл, которое ведет к их реорганизации, также влияет на форму и прозрачность роговицы. При кератоконусе обнаружено уменьшение общего количества коллагена, коллагена I и III типа, повышение уровня XV и снижение уровня IV типа коллагена с изменением соотношения между ними в строме роговицы, а также аллельные различия в генах COL4A3 и CoL4A4, кодирующих синтез двух из шести α-цепей молекулы коллагена IV типа. Кроме того, обнаружены нуклеотидные полиморфизмы в строении генов LOX, программирующих синтез лизилоксидазы и лизилоксидазоподобных ферментов, отвечающих за поперечную сшивку полипептидных цепей коллагена, что усиливает механическую прочность фибрилл. Дефицит активности генов LOX также выявляется у пациентов с определенными формами дисплазий соединительной ткани, обусловливая системные нарушения ее биомеханических свойств. Дальнейшие исследования в области этиологии этих заболеваний дадут возможность своевременно выявлять и проводить патогенетически ориентированную терапию генетических нарушений, связанных с аномалией тканевых структур. 

Common association of keratoconus and connective tissue dysplasia indicates that these disorders possibly share etiology and pathogenesis. Connective tissue dysplasia is characterized by the decrease in certain types of collagen, abnormalities of their proportion, alteration of collagen synthesis and assembly, immature collagen synthesis, abnormalities of collagen fiber structure, defects of type III collagen synthesis, peptidase deficiency, and increase in pro-collagen as compared with collagen. The latter accounts for immature collagen level increase in tissues and organs and systemic congenital laxity of connective tissue. This results in the abnormalities of biomechanical properties of organs and tissues which are composed of collagen fibers. Corneal stroma consists of collagen fibers and glycoprotein matrix. Hence, quantitative and qualitative changes in connective tissue dysplasia affect corneal biomechanics. Abnormalities of collagen fibril orientation result in their reorganization thus influencing corneal shape and transparency. In keratoconus, decreased total collagen and type I, type III, and type IV collagen, increased type XV collagen, and abnormalities of their proportion in corneal stroma as well as allele differences in COL4A3 and CoL4A4 genes encoding 2 of 6 α-chains of type IV collagen were demonstrated. Nucleotide polymorphisms in LOX genes encoding lysyl oxidase and lysyl oxidase-like enzymes which are responsible for cross-linking of collagen polypeptide chains (and, therefore, mechanical strength of fibrils) were revealed as well. LOX gene deficiency that accounts for systemic biomechanical abnormalities was also recognized in certain connective tissue dysplasia. Further studies will provide early diagnosis and pathogenically target therapy of genetic disorders associated with tissue abnormalities 

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The authors declare that there are no conflicts of interest present.