Bidirectional Expression of Metabolic, Structural, and Immune Pathways in Early Myopia and Hyperopia

Abstract

Myopia (short-sightedness) affects 1.45 billion people worldwide, many of whom will develop sight-threatening secondary disorders. Myopic eyes are characterized by excessive size while hyperopic (long-sighted) eyes are typically small. The biological and genetic mechanisms underpinning the retina's local control of these growth patterns remain unclear. In the present study, we used RNA sequencing to examine gene expression in the retina/RPE/choroid across 3 days of optically-induced myopia and hyperopia induction in chick. Data were analyzed for differential expression of single genes, and Gene Set Enrichment Analysis (GSEA) was used to identify gene sets correlated with ocular axial length and refraction across lens groups. Like previous studies, we found few single genes that were differentially-expressed in a sign-of-defocus dependent manner (only BMP2 at 1 day). Using GSEA, however, we are the first to show that more subtle shifts in structural, metabolic, and immune pathway expression are correlated with the eye size and refractive changes induced by lens defocus. Our findings link gene expression with the morphological characteristics of refractive error, and suggest that physiological stress arising from metabolic and inflammatory pathway activation could increase the vulnerability of myopic eyes to secondary pathologies.

Circadian rhythms, refractive development, and myopia

“…This review will concentrate on myopia (i.e., nearsightedness) because its prevalence is high, it is associated with significant ocular complications, and most recent research addresses mechanisms for myopia development as distinct from hyperopia (i.e., farsightedness). Importantly, considerable literature suggests that the mechanisms responsible for myopia vs hyperopia are not just reciprocal, but may be different …”

Integrated Comparison of GWAS, Transcriptome, and Proteomics Studies Highlights Similarities in the Biological Basis of Animal and Human Myopia

“…[14][15][16][17][18] Concurrently, the role of visual experience in adapting ocular growth to suit the environment has been extensively investigated in animals where myopia can be induced by rearing with form deprivation occluders or negatively powered defocusing lenses. 19 Transcriptome and proteomics studies of ocular expression profiles in these animal models have associated thousands of genes [20][21][22][23][24][25][26][27][28] and hundreds of proteins [29][30][31][32][33][34][35][36][37] with environmentally driven growth. Enrichment analyses have aided interpretation of the wealth of data generated by exploratory human and animal studies 20,38 ; however, the key pathways by which genes and environment control ocular growth remain largely unclear.…”

Analysis of genetic networks regulating refractive eye development in collaborative cross progenitor strain mice reveals new genes and pathways underlying human myopia

“…These loci implicate genes involved in multiple cellular and biological processes related to extracellular matrix organization, eye morphogenesis, retinal signaling, and visual perception [53,54]. Gene expression profiling studies also showed that development of myopia is accompanied by changes in gene expression in the retina, choroid, and sclera [39,[55][56][57][58][59][60][61][62].…”