Influence of light and autonomic innervation on growth factor expression in chick choroid

Abstract

Purpose : Emmetropization is guided by visual input leading to changes in ocular growth rates. Unknown retinal growth signals are transferred into the sclera, with the choroid as an intermediary. Growth regulation depends on growth factor expression, but also on vascular supply, and hence on choroidal blood flow that is regulated by the autonomic nervous system. While light stimulation alters choroidal blood flow, we ask if different light stimuli influence choroidal growth factor expression and we tested for the role of the autonomic nervous system in this context.

Methods : White Leghorns (1 to 2 weeks old) received unilateral lesion of the ocular parasympathetic (ciliary/pterygopalatine ganglion; n=20) or sympathetic (superior cervical ganglion; n=26) pathways. Following recovery (1 week), chicks were exposed to steady yellow light (y; n=10; mean illumination 680 lux) or sinusoidal modulated light (2Hz: 80% contrast) that changed in luminance contrast (yellow to black; yk; n=19) or color contrast (yellow to blue; yb; n=17). Chicks were kept in these conditions (3 days, 9am-5pm; otherwise in dark) and sacrificed immediately after light cycle. Choroids (n≥5/group) were removed and prepared for quantitative RT-PCR of BMP2, IGF1, EGF, PDGFA, PDGFB, PDGFC, TGFB1, TGFB2, TGFB3, VEGFA, VEGFC. Relative gene expression levels were determined (normalized to HPRT) followed by statistical analysis (t-test or Wilcoxon test; ANOVA) to compare lesioned vs non-lesioned eyes.

Results : In parasympathetic lesion, EGF, IGF1, and TGFB1 were up-regulated (p≤0.05) in at least one light condition (y: EGF, IGF1, TGFB1; yk: IGF1; yb: EGF, IGF1). In contrast, in sympathetic lesion, expression of EGF, IGF1, PDGFC, TGFB2, and VEGFA was down-regulated (p≤0.05); however, this effect occurred in flicker conditions only (yk: EGF, IGF1, TGFB2, VEGFA; yb: EGF, PDGFC, TGFB2, VEGFA), but not in steady light (y). No change in any condition (lesion and light) was seen for BMP2, PDGFA/B, TGFB3, and VEGFC.

Conclusions : In response to different light conditions, lesion of ocular autonomic innervation changed expression of choroidal growth factors. Effects differed in sympathetic and parasympathetic lesions. More extensive expression analysis will be necessary to link these results with physiological events like light-induced changes in choroidal blood flow and to clarify the role of the autonomic nervous system in light-induced ocular growth changes.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.