Light- and focus-dependent expression of the transcription factor ZENK in the chick retina

Abstract

Ocular growth and refraction are regulated by visual processing in the retina. We identified candidate regulatory neurons by immunocytochemistry for immediate-early gene products, ZENK (zif268, Egr-1) and Fos, after appropriate visual stimulation. ZENK synthesis was enhanced by conditions that suppress ocular elongation (plus defocus, termination of form deprivation) and suppressed by conditions that enhance ocular elongation (minus defocus, form deprivation), particularly in glucagon-containing amacrine cells. Fos synthesis was enhanced by termination of visual deprivation, but not by defocus and not in glucagon-containing amacrine cells. We conclude that glucagon-containing amacrine cells respond differentially to the sign of defocus and may mediate lens-induced changes in ocular growth and refraction.

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

“…These reports suggest that the retina can perceive the defocus and evoke signals to accelerate the progression of myopia. This hypothesis is supported by animal experiments that show amacrine cells and their transcription factor, ZENK, have important roles in the perception of retinal defocus 20,21 . Nevertheless, the mechanisms by which these signals are transduced are not yet known.…”

“…Considering that the effect of WNT7B rs10453441 on myopia through axial length is in the opposite direction to that through corneal curvature, WNT7B may be under strict control to correlate the anterior and posterior segments in the emmetropization of the eye. To date, accumulating evidence suggests that retinal image defocus is the trigger for myopia, and the role of amacrine cells in delivering an image defocus signal has been intensively investigated in the context of myopia development 20,21,41 . Nevertheless, the precise mechanisms mediating the transduction of this defocus signal leading to myopia are still unclear.…”

Controversial opinion: evaluation of EGR1 and LAMA2 loci for high myopia in Chinese populations

“…The gene knockout mice model demonstrated that EGR1 played a role in experimental axial myopia (Schippert et al, 2007). Fischer et al (1999) also found a significant association of the EGR1 expression level in the retina with eyeball growth in the animal model. Moreover, a recent myopia animal study indicated that EGR1 might play a role in signaling eye growth bidirectionally (Ashby et al, 2014).…”

“…We chose EGR1 as a candidate gene for association analysis of myopia, based on its functionality evidence: (1) Animal model studies of induced myopia and gene knock-out have all demonstrated the important role of EGR1 in myopia (Schippert et al, 2007); (2) EGR1 is a critical protein for eye growth and myopisation (Fischer et al, 1999;Ashby et al, 2014). The SNP rs11743810 selected here is itself the tSNP covering the EGR1 gene region's LD plot with an r 2 of 1.000 00 and an estimated power for association test of 0.997 83 (Table 4), suggesting the high efficiency of the association analysis.…”

Genetic background-dependent role of Egr1 for eyelid development

“…Interestingly, in chicks exposed to positive or negative lenses to induce defocus, Egr1 expression was increased with positive lenses that suppress ocular elongation and decreased with negative lenses that enhance ocular elongation (29,30).…”