Important anatomical, age-related, and species considerations regarding ocular fibulin-3 (EFEMP1) analysis

Abstract

Purpose: Fibulin-3 (F3) or EFEMP1 is a secreted extracellular matrix glycoprotein implicated in several ocular diseases. Little is known about the native biology of this protein. Thus, our study aims to determine expression and localization characteristics of F3 utilizing a range of mammalian species as well as F3-associated changes with age. Methods: Gene expression analyses for fibulins as well as immunohistochemistry for F3 were conducted in ocular tissue from mice, pigs, non-human primates (NHPs), and humans (n = 3-5). Age-based F3 expression study along with changes in ECM remodeling enzymes was also evaluated in mice. Results: Within the mouse retina, F3 staining was consistent throughout the entirety of the retina (far-periphery, mid-periphery, and central), being enriched in the ganglion cell layer and inner nuclear layer (INL). However, in humans, the F3 staining pattern was quite unique; enriched in the RPE, INL, and outer nuclear layer (ONL) in the peripheral retina, but then shifting to predominantly outer plexiform layer (OPL) staining in the central retina and macula with waning RPE immunoreactivity approaching the fovea. We demonstrate that F3 expression in the mouse retina significantly increases with age, and the levels of extracellular F3 degrading enzymes produced by the RPE and retina (e.g., Mmp2 and Htra1) decrease with age. Conclusions: These findings demonstrate that F3 has distinct species-dependent as well as ocular region-specific expression and localization patterns. We also show that F3 and ECM enzyme dynamics favor F3 accumulation in the retina and RPE with increasing age.

Familial Dominant Drusen: Novel Data on Pathogenesis (Literature Review and Clinical Case Presentation)

“…В норме с возрастом в сетчатке наблюдается увеличение экспрессии EFEMP1. Ввиду того факта, что фибулин-3 выступает в качестве важного модулятора биологии соединительнотканных структур, генетические варианты FBLN3 связаны со множеством заболеваний человека в различных системах органов; аллели EFEMP1 тесно ассоциированы с развитием первичной открытоугольной глаукомы и ювенильной открытоугольной глаукомы [7,8,13,16,[22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Данные о коморбидности сотовидной дистрофии сетчатки с нейродегенеративными заболеваниями в доступной литературе отсутствуют, что говорит о вовлечении в патологический процесс исключительно нейральных элементов сетчатки, но не зрительного нерва и не структур центральной нервной системы.…”