Gene Expression Associated with Lens–Induced Myopia in Rhesus Monkeys

Abstract

Abstract: : Purpose:To identify genes that may modulate lens induced ocular growth in infantile Rhesus monkeys. Methods:Two infant rhesus monkeys were raised with goggles fitted with progressively stronger plus lenses over their right eyes (+3, +4.5, and +6 D) and minus lenses over their left eyes (–1.5 and –3 D). The monkeys also received alternating occlusion for half of each day in each eye. After wearing lenses for 103–122 days they were then sacrificed and the retinal mRNA from the eyes wearing plus lenses were compared to the eyes wearing minus lenses using Affymetrix GeneChip microarrays. Results: Monkeys developed 2–4 D of relative myopia in the eyes wearing the minus lenses. Significant differences in the retinal levels of mRNA coding for tyrosine 3–monoxygenase/ tryptophan 5–monoxygenase activator protein (3.6 log increase), calcitonin gene–related peptide–receptor component protein (1.4 log decrease), type 1 cAMP–dependent protein kinase regulatory subunit (1.0 log increase) and voltage–dependent, calcium channel, beta 2 subunit (3.3 log increase) were found between the eyes wearing plus and minus lenses. Conclusions:Signficant differences in transcripts encoding a number of proteins, which may be important for ocular growth, were found between eyes wearing plus and minus lenses. Tyrosine 3–monooxygenase/ tryptophan 5–monoxygenase activator protein is involved in dopamine synthesis, which has been implicated in the development of form–deprivation myopia. Calcitonin gene–related peptide–receptor component protein is contained in ophthalmic sensory nerve fibers that innervate the choroid and regulate the vasodilation of choroidal blood vessels. In chicks, tree shrews and higher primates, choroidal thickness has been shown to compensate for optically induced refractive errors. The other two proteins are involved in signal transduction. Conceivably they could regulate the transmission of signals from the retina to the retinal pigment epithelium and choroid. Further studies are planned to determine the significance of these proteins for ocular growth in non–human primates.

Keywords: myopia • gene microarray • growth factors/growth factor receptors