Retinal Gene Expression in Chick Myopia

Abstract

Purpose:: Stimulated by evidence implicating the retina as a principal controller of refractive development, we used microarrays to analyze the chick retinal transcriptome and identify potential signaling pathways altered in form-deprivation myopia.

Methods:: Week-old white Leghorn chicks wore a unilateral image-degrading goggle for 6 hours or 3 days (n=6 at each time). Affymetrix chicken genome microarrays were used to screen total RNA from the retina/(retinal pigment epithelium). Gene expression was compared in goggled vs. non-goggled eyes by two statistical approaches and validated by real-time quantitative reverse transcription-polymerase chain reaction (qPCR) in independent biological replicates.

Results:: Only a modest number of genes were differentially expressed and their fold-hanges were small. Validated as down-regulated in form-deprived eyes were: bone morphogenetic protein 2 and connective tissue growth factor after 6 hours of goggle wear; and mitogen-activated protein kinase phosphatase 2 and vasoactive intestinal peptide after 3 days of goggle wear.

Conclusions:: Form-deprivation myopia, in its early stages, is associated with only minimal changes in retinal gene expression. The different profiling results after six hours and three days of goggle wear raise the question of whether the signals that initiate myopia differ from those that maintain its progression. Interestingly, the VIP receptor 2 and the BMP type IB receptor map to the regions of human MYP4 and MYP11 loci, respectively, and could be regarded as candidate genes for future research. Considered with other retinal profiling studies in chicks and monkeys, however, major changes in retinal gene expression levels may not be necessary for myopia to develop following environmental insults. While the list of candidate genes found by microarray profiling is short, each validated gene merits further study for potential involvement in the signaling cascade mediating myopia development.

Keywords: myopia • retina: neurochemistry • gene microarray