Egr-1 mRNA expression is a marker for the direction of mammalian ocular growth

Invest Ophthalmol Vis Sci. 2014 Jul 22;55(9):5911-21. doi: 10.1167/iovs.13-11708.

Abstract

Purpose: The immediate early gene Egr-1 is thought to form part of the pathway that mediates abnormal ocular growth. This study investigated whether the mRNA expression levels of Egr-1 in a mammalian retina are modulated differentially, depending on the direction of ocular growth.

Methods: To induce accelerated growth and myopia, guinea pigs wore a -5 diopter (D) lens over one eye from 4 to 11 days of age. To induce inhibited growth, the lens was removed after 7 days of -5 D lens wear, and the eye allowed to recover from myopia for 3 days. Ocular parameters and Egr-1 mRNA levels were subsequently assessed, and compared to untreated fellow eyes and eyes from untreated littermates. Possible circadian changes in Egr-1 mRNA levels were also determined in 18 additional animals by taking measures every 4 hours during a 24-hour cycle.

Results: Ocular compensation to a -5 D lens occurred after 7 days (Δ -4.8 D, Δ +147 μm growth, N = 20). In 5 highly myopic eyes (Δ -7.4 D), Egr-1 mRNA levels in the retina were significantly downregulated relative to contralateral control (51%) and age-matched untreated (47%) eyes. Three days after the -5 D lens was removed, eyes had recovered from the myopia (Δ -0.5 D, relative change of +2.9 D, N = 4) and Egr-1 mRNA levels were significantly elevated relative to contralateral (212%) and untreated (234%) eyes, respectively. Normal Egr-1 mRNA expression was higher in the middle of the day than in the middle of the night. Immunolabeling showed strong Egr-1 reactivity in cell bodies in the inner nuclear and ganglion cell layers.

Conclusions: Egr-1 mRNA levels in a mammalian retina show a bi-directional persistent response to opposing ocular growth stimuli. This suggests retinal Egr-1 might act as a signal for the direction of ocular growth in different species.

Keywords: Egr-1; guinea pig; myopia; refractive error; retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Biomarkers / metabolism
  • Circadian Rhythm / physiology
  • Disease Models, Animal
  • Early Growth Response Protein 1 / metabolism*
  • Eye / growth & development*
  • Guinea Pigs
  • Immunohistochemistry
  • Myopia / metabolism*
  • RNA, Messenger / metabolism
  • Retina / metabolism*

Substances

  • Biomarkers
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • RNA, Messenger